Trial Outcomes & Findings for A Study of Oral Rucaparib in Patients With a Solid Tumor (Phase I) or With gBRCA Mutation Ovarian Cancer (Phase II) (NCT NCT01482715)

Last Updated: 2023-06-09

Results Overview

The confirmed response rate by RECIST v1.1 is defined as the proportion of patients with a confirmed Complete Response (CR) or Partial Response (PR) on subsequent tumor assessment at least 28 days after first response documentation.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

136 participants

Primary outcome timeframe

Time from first dose to date of progression, up to approximately 8 months

Results posted on

2023-06-09

Participant Flow

The study was conducted at 15 investigative sites in the United States (6 sites), United Kingdom (5 sites), Spain (1 site), Israel (2 sites), and Canada (1 site).

Participant milestones

Participant milestones
Measure	Rucaparib 40 mg QD (Part 1) Rucaparib 40 mg once a day (QD) for continuous 21-day cycles	Rucaparib 80 mg QD (Part 1) Rucaparib 80 mg once a day (QD) for continuous 21-day cycles	Rucaparib 160 mg QD (Part 1) Rucaparib 160 mg once a day (QD) for continuous 21-day cycles	Rucaparib 300 mg QD (Part 1) Rucaparib 300 mg once a day (QD) for continuous 21-day cycles	Rucaparib 500 mg QD (Part 1) Rucaparib 500 mg once a day (QD) for continuous 21-day cycles	Rucaparib 240 mg BID (Part 1) Rucaparib 240 mg twice a day (BID) for continuous 21-day cycles	Rucaparib 360 mg BID (Part 1) Rucaparib 360 mg twice a day (BID) for continuous 21-day cycles	Rucaparib 480 mg BID (Part 1) Rucaparib 480 mg twice a day (BID) for continuous 21-day cycles	Rucaparib 600 mg BID (Part 1) Rucaparib 600 mg twice a day (BID) for continuous 21-day cycles	Rucaparib 840 mg BID (Part 1) Rucaparib 840 mg twice a day (BID) for continuous 21-day cycles	Rucaparib 600 mg BID (Part 2A) Rucaparib 600 mg twice a day (BID) for 21-day cycles	Rucaparib 600 mg BID (Part 2B) Rucaparib 600 mg twice a day (BID) for 21-day cycles	Rucaparib 600 mg BID (Part 3) Rucaparib 600 mg twice a day (BID) for 21-day cycles. Patients also received a single administration of 600 mg rucaparib on both Day -7 and Day 1 for assessing the effect of food on PK.
Overall Study STARTED	6	3	4	9	4	3	8	9	7	3	42	12	26
Overall Study COMPLETED	6	3	4	9	4	3	8	9	7	3	42	12	26
Overall Study NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of Oral Rucaparib in Patients With a Solid Tumor (Phase I) or With gBRCA Mutation Ovarian Cancer (Phase II)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rucaparib 40 mg QD (Part 1) n=6 Participants Rucaparib 40 mg QD for continuous 21-day cycles	Rucaparib 80 mg QD (Part 1) n=3 Participants Rucaparib 80 mg QD for continuous 21-day cycles	Rucaparib 160 mg QD (Part 1) n=4 Participants Rucaparib 160 mg QD for continuous 21-day cycles	Rucaparib 300 mg QD (Part 1) n=9 Participants Rucaparib 300 mg QD for continuous 21-day cycles	Rucaparib 500 mg QD (Part 1) n=4 Participants Rucaparib 500 mg QD for continuous 21-day cycles	Rucaparib 240 mg BID (Part 1) n=3 Participants Rucaparib 240 mg BID for continuous 21-day cycles	Rucaparib 360 mg BID (Part 1) n=8 Participants Rucaparib 360 mg BID for continuous 21-day cycles	Rucaparib 480 mg BID (Part 1) n=9 Participants Rucaparib 480 mg BID for continuous 21-day cycles	Rucaparib 600 mg BID (Part 1) n=7 Participants Rucaparib 600 mg BID for continuous 21-day cycles	Rucaparib 840 mg BID (Part 1) n=3 Participants Rucaparib 840 mg BID for continuous 21-day cycles	Rucaparib 600 mg BID (Part 2A) n=42 Participants Rucaparib 600 mg BID for continuous 21-day cycles	Rucaparib 600 mg BID (Part 2B) n=12 Participants Rucaparib 600 mg BID for continuous 21-day cycles	Rucaparib 600 mg BID (Part 3) n=26 Participants Rucaparib 600 mg BID for continuous 21-day cycles	Total n=136 Participants Total of all reporting groups
Age, Continuous	63.5 years n=5 Participants	46.0 years n=7 Participants	52.0 years n=5 Participants	48.0 years n=4 Participants	29.5 years n=21 Participants	64.0 years n=10 Participants	49.5 years n=115 Participants	46.0 years n=24 Participants	52.0 years n=42 Participants	55.0 years n=42 Participants	56.5 years n=42 Participants	57.5 years n=42 Participants	59.5 years n=36 Participants	57.0 years n=36 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	9 Participants n=4 Participants	2 Participants n=21 Participants	2 Participants n=10 Participants	7 Participants n=115 Participants	9 Participants n=24 Participants	7 Participants n=42 Participants	2 Participants n=42 Participants	42 Participants n=42 Participants	12 Participants n=42 Participants	21 Participants n=36 Participants	126 Participants n=36 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants	1 Participants n=10 Participants	1 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	1 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	5 Participants n=36 Participants	10 Participants n=36 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=36 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants	1 Participants n=24 Participants	0 Participants n=42 Participants	1 Participants n=42 Participants	3 Participants n=42 Participants	0 Participants n=42 Participants	1 Participants n=36 Participants	7 Participants n=36 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=36 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	3 Participants n=42 Participants	0 Participants n=42 Participants	2 Participants n=36 Participants	9 Participants n=36 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	7 Participants n=4 Participants	3 Participants n=21 Participants	3 Participants n=10 Participants	6 Participants n=115 Participants	8 Participants n=24 Participants	7 Participants n=42 Participants	2 Participants n=42 Participants	35 Participants n=42 Participants	11 Participants n=42 Participants	22 Participants n=36 Participants	117 Participants n=36 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	1 Participants n=42 Participants	0 Participants n=42 Participants	1 Participants n=36 Participants	2 Participants n=36 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	1 Participants n=42 Participants	0 Participants n=36 Participants	1 Participants n=36 Participants

PRIMARY outcome

Timeframe: Time from first dose to date of progression, up to approximately 8 months

Population: Efficacy-Evaluable Population - all Part 2 patients who met eligibility criteria, received at least 1 dose of rucaparib, had measurable tumor lesions at baseline, and had at least 1 post-baseline disease assessment. 2 patients in Part 2A discontinued treatment due to an AE and did not have a post-baseline disease assessment.

Outcome measures

Outcome measures
Measure	Rucaparib 600 mg BID (Part 2A) n=40 Participants Rucaparib 600 mg BID for 21-day cycles	Rucaparib 600 mg BID (Part 2B) n=12 Participants Rucaparib 600 mg BID for 21-day cycles	Rucaparib 160 mg QD (Part 1) Rucaparib 160 mg once a day (QD)	Rucaparib 300 mg QD (Part 1) Rucaparib 300 mg once a day (QD)	Rucaparib 500 mg QD (Part 1) Rucaparib 500 mg once a day (QD)	Rucaparib 240 mg BID (Part 1) Rucaparib 240 mg twice a day (BID)	Rucaparib 360 mg BID (Part 1) Rucaparib 360 mg twice a day (BID)	Rucaparib 480 mg BID (Part 1) Rucaparib 480 mg twice a day (BID)	Rucaparib 600 mg BID (Part 1) Rucaparib 600 mg twice a day (BID)	Rucaparib 840 mg BID (Part 1) Rucaparib 840 mg twice a day (BID)
Overall Response Rate Per RECIST Version 1.1 (Part 2)	25 Participants	7 Participants	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 1 to Cycle 1 Day 21

Population: DLT-evaluable population - all patients enrolled into Part 1 of the study who received at least 17 complete days of rucaparib and completed Cycle 1 of treatment, or who experienced a DLT in Cycle 1.

The number of Part 1 (Phase 1) patients who experienced dose limiting toxicities after one cycle (21 days) of study drug.

Outcome measures

Outcome measures
Measure	Rucaparib 600 mg BID (Part 2A) n=6 Participants Rucaparib 600 mg BID for 21-day cycles	Rucaparib 600 mg BID (Part 2B) n=3 Participants Rucaparib 600 mg BID for 21-day cycles	Rucaparib 160 mg QD (Part 1) n=4 Participants Rucaparib 160 mg once a day (QD)	Rucaparib 300 mg QD (Part 1) n=9 Participants Rucaparib 300 mg once a day (QD)	Rucaparib 500 mg QD (Part 1) n=4 Participants Rucaparib 500 mg once a day (QD)	Rucaparib 240 mg BID (Part 1) n=3 Participants Rucaparib 240 mg twice a day (BID)	Rucaparib 360 mg BID (Part 1) n=8 Participants Rucaparib 360 mg twice a day (BID)	Rucaparib 480 mg BID (Part 1) n=9 Participants Rucaparib 480 mg twice a day (BID)	Rucaparib 600 mg BID (Part 1) n=7 Participants Rucaparib 600 mg twice a day (BID)	Rucaparib 840 mg BID (Part 1) n=3 Participants Rucaparib 840 mg twice a day (BID)
Number of Participants With a Dose Limiting Toxicity (DLT)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days

Population: PK-evaluable population - all patients enrolled into Part 1 of the study who received at least one dose of rucaparib and had adequate PK assessments drawn for determination of the PK profile. For some arms, the number analyzed at Day 1 and Day 15 differs from the overall number based on number of evaluable samples collected at each time point.

Cmax = maximum concentration following administration of rucaparib

Outcome measures

Outcome measures
Measure	Rucaparib 600 mg BID (Part 2A) n=3 Participants Rucaparib 600 mg BID for 21-day cycles	Rucaparib 600 mg BID (Part 2B) n=3 Participants Rucaparib 600 mg BID for 21-day cycles	Rucaparib 160 mg QD (Part 1) n=4 Participants Rucaparib 160 mg once a day (QD)	Rucaparib 300 mg QD (Part 1) n=3 Participants Rucaparib 300 mg once a day (QD)	Rucaparib 500 mg QD (Part 1) n=3 Participants Rucaparib 500 mg once a day (QD)	Rucaparib 240 mg BID (Part 1) n=3 Participants Rucaparib 240 mg twice a day (BID)	Rucaparib 360 mg BID (Part 1) n=8 Participants Rucaparib 360 mg twice a day (BID)	Rucaparib 480 mg BID (Part 1) n=9 Participants Rucaparib 480 mg twice a day (BID)	Rucaparib 600 mg BID (Part 1) n=7 Participants Rucaparib 600 mg twice a day (BID)	Rucaparib 840 mg BID (Part 1) n=3 Participants Rucaparib 840 mg twice a day (BID)
PK Profile of Rucaparib - Cmax (Part 1) Day 1 Cmax	120 ng/mL Interval 98.9 to 168.0	119 ng/mL Interval 65.7 to 158.0	255 ng/mL Interval 107.0 to 426.0	700 ng/mL Interval 368.0 to 818.0	699 ng/mL Interval 629.0 to 1520.0	132 ng/mL Interval 123.0 to 401.0	603 ng/mL Interval 244.0 to 1170.0	1090 ng/mL Interval 312.0 to 2440.0	972 ng/mL Interval 271.0 to 1790.0	954 ng/mL Interval 705.0 to 2470.0
PK Profile of Rucaparib - Cmax (Part 1) Day 15 Cmax	159 ng/mL Interval 80.7 to 174.0	180 ng/mL Interval 108.0 to 237.0	267 ng/mL Interval 217.0 to 380.0	439 ng/mL Interval 340.0 to 1300.0	1250 ng/mL Interval 1170.0 to 1750.0	783 ng/mL Interval 619.0 to 1510.0	1220 ng/mL Interval 728.0 to 2320.0	2480 ng/mL Interval 922.0 to 6870.0	2330 ng/mL Interval 477.0 to 3670.0	3030 ng/mL Interval 3000.0 to 3060.0

PRIMARY outcome

Timeframe: Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days

Tmax = time to maximum concentration following administration of rucaparib

Outcome measures

Outcome measures
Measure	Rucaparib 600 mg BID (Part 2A) n=3 Participants Rucaparib 600 mg BID for 21-day cycles	Rucaparib 600 mg BID (Part 2B) n=3 Participants Rucaparib 600 mg BID for 21-day cycles	Rucaparib 160 mg QD (Part 1) n=4 Participants Rucaparib 160 mg once a day (QD)	Rucaparib 300 mg QD (Part 1) n=3 Participants Rucaparib 300 mg once a day (QD)	Rucaparib 500 mg QD (Part 1) n=3 Participants Rucaparib 500 mg once a day (QD)	Rucaparib 240 mg BID (Part 1) n=3 Participants Rucaparib 240 mg twice a day (BID)	Rucaparib 360 mg BID (Part 1) n=8 Participants Rucaparib 360 mg twice a day (BID)	Rucaparib 480 mg BID (Part 1) n=9 Participants Rucaparib 480 mg twice a day (BID)	Rucaparib 600 mg BID (Part 1) n=7 Participants Rucaparib 600 mg twice a day (BID)	Rucaparib 840 mg BID (Part 1) n=3 Participants Rucaparib 840 mg twice a day (BID)
PK Profile of Rucaparib - Tmax (Part 1) Day 1 Tmax	2.5 hr Interval 1.0 to 4.0	1.5 hr Interval 1.0 to 2.5	4 hr Interval 4.0 to 6.05	2.5 hr Interval 1.0 to 4.08	4 hr Interval 4.0 to 4.0	6 hr Interval 4.05 to 6.0	3.23 hr Interval 1.5 to 6.0	2.5 hr Interval 1.5 to 4.0	4 hr Interval 2.42 to 10.0	4 hr Interval 2.5 to 8.0
PK Profile of Rucaparib - Tmax (Part 1) Day 15 Tmax	4 hr Interval 1.0 to 4.05	2.5 hr Interval 2.5 to 2.57	3.75 hr Interval 2.5 to 4.0	2.53 hr Interval 2.5 to 8.0	4 hr Interval 4.0 to 4.17	1.5 hr Interval 1.0 to 4.0	3.3 hr Interval 0.0 to 6.33	1.51 hr Interval 0.0 to 6.0	4 hr Interval 2.53 to 10.0	4.04 hr Interval 4.0 to 4.07

PRIMARY outcome

Timeframe: Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days

AUC last = Area under the plasma concentration-time curve from time 0 to the last recorded observation

Outcome measures

Outcome measures
Measure	Rucaparib 600 mg BID (Part 2A) n=3 Participants Rucaparib 600 mg BID for 21-day cycles	Rucaparib 600 mg BID (Part 2B) n=3 Participants Rucaparib 600 mg BID for 21-day cycles	Rucaparib 160 mg QD (Part 1) n=4 Participants Rucaparib 160 mg once a day (QD)	Rucaparib 300 mg QD (Part 1) n=3 Participants Rucaparib 300 mg once a day (QD)	Rucaparib 500 mg QD (Part 1) n=3 Participants Rucaparib 500 mg once a day (QD)	Rucaparib 240 mg BID (Part 1) n=3 Participants Rucaparib 240 mg twice a day (BID)	Rucaparib 360 mg BID (Part 1) n=8 Participants Rucaparib 360 mg twice a day (BID)	Rucaparib 480 mg BID (Part 1) n=9 Participants Rucaparib 480 mg twice a day (BID)	Rucaparib 600 mg BID (Part 1) n=7 Participants Rucaparib 600 mg twice a day (BID)	Rucaparib 840 mg BID (Part 1) n=3 Participants Rucaparib 840 mg twice a day (BID)
PK Profile of Rucaparib - AUC Last (Part 1) Day 15 AUC last	2270 hr*ng/mL Interval 889.0 to 2280.0	1870 hr*ng/mL Interval 1340.0 to 2000.0	3510 hr*ng/mL Interval 3130.0 to 5670.0	6090 hr*ng/mL Interval 4020.0 to 18700.0	16500 hr*ng/mL Interval 13900.0 to 29200.0	6340 hr*ng/mL Interval 5100.0 to 12600.0	9110 hr*ng/mL Interval 5950.0 to 17200.0	19400 hr*ng/mL Interval 7480.0 to 55100.0	19700 hr*ng/mL Interval 3090.0 to 32600.0	24900 hr*ng/mL Interval 24100.0 to 25700.0
PK Profile of Rucaparib - AUC Last (Part 1) Day 1 AUC last	915 hr*ng/mL Interval 850.0 to 981.0	916 hr*ng/mL Interval 555.0 to 930.0	2730 hr*ng/mL Interval 1520.0 to 5230.0	5820 hr*ng/mL Interval 3540.0 to 7860.0	7670 hr*ng/mL Interval 6640.0 to 18700.0	875 hr*ng/mL Interval 835.0 to 2430.0	4160 hr*ng/mL Interval 1060.0 to 6670.0	6190 hr*ng/mL Interval 1270.0 to 17200.0	6700 hr*ng/mL Interval 1650.0 to 10900.0	5930 hr*ng/mL Interval 5140.0 to 16700.0

SECONDARY outcome

Timeframe: Cycle 1 Day 1 to End of Treatment, up to approximately 51 months

Population: Safety population: Consist of all Part 2 patients who received at least one dose of rucaparib

PFS is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST, as determined by the investigator or death due to any cause, whichever occurs first.

Outcome measures

Outcome measures
Measure	Rucaparib 600 mg BID (Part 2A) n=42 Participants Rucaparib 600 mg BID for 21-day cycles	Rucaparib 600 mg BID (Part 2B) n=12 Participants Rucaparib 600 mg BID for 21-day cycles	Rucaparib 160 mg QD (Part 1) Rucaparib 160 mg once a day (QD)	Rucaparib 300 mg QD (Part 1) Rucaparib 300 mg once a day (QD)	Rucaparib 500 mg QD (Part 1) Rucaparib 500 mg once a day (QD)	Rucaparib 240 mg BID (Part 1) Rucaparib 240 mg twice a day (BID)	Rucaparib 360 mg BID (Part 1) Rucaparib 360 mg twice a day (BID)	Rucaparib 480 mg BID (Part 1) Rucaparib 480 mg twice a day (BID)	Rucaparib 600 mg BID (Part 1) Rucaparib 600 mg twice a day (BID)	Rucaparib 840 mg BID (Part 1) Rucaparib 840 mg twice a day (BID)
Progression-free Survival (PFS) According to RECIST v1.1, as Assessed by the Investigator (Part 2)	260 Days Interval 203.0 to 373.0	280 Days Interval 40.0 to 551.0	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 Day 1 to End of Treatment, up to approximately 48 months

Population: Safety population - all Part 2 patients with confirmed response per investigator.

Duration of response (DOR) for any confirmed RECIST CR or PR measured from the date of the first occurrence of a response until the first occurrence of PD per RECIST. For patients who continued treatment post-progression, the first date of progression was used for the analysis. Any patients with an ongoing response were censored at the date of the last post-baseline scan.

Outcome measures

Outcome measures
Measure	Rucaparib 600 mg BID (Part 2A) n=25 Participants Rucaparib 600 mg BID for 21-day cycles	Rucaparib 600 mg BID (Part 2B) n=7 Participants Rucaparib 600 mg BID for 21-day cycles	Rucaparib 160 mg QD (Part 1) Rucaparib 160 mg once a day (QD)	Rucaparib 300 mg QD (Part 1) Rucaparib 300 mg once a day (QD)	Rucaparib 500 mg QD (Part 1) Rucaparib 500 mg once a day (QD)	Rucaparib 240 mg BID (Part 1) Rucaparib 240 mg twice a day (BID)	Rucaparib 360 mg BID (Part 1) Rucaparib 360 mg twice a day (BID)	Rucaparib 480 mg BID (Part 1) Rucaparib 480 mg twice a day (BID)	Rucaparib 600 mg BID (Part 1) Rucaparib 600 mg twice a day (BID)	Rucaparib 840 mg BID (Part 1) Rucaparib 840 mg twice a day (BID)
Duration of Response Per RECIST Version 1.1 (Part 2)	270 Days Interval 170.0 to 393.0	318 Days Interval 106.0 to 497.0	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 Day 1 to date of death, assessed up to 38 months

Population: Safety population: Consist of all Part 2B patients who received at least one dose of rucaparib

Overall survival (OS) is defined as the number of days from the date of first dose of study drug to the date of death, due to any cause. Patients without a documented event of death will be censored on the date of their last visit.

Outcome measures

Outcome measures
Measure	Rucaparib 600 mg BID (Part 2A) n=12 Participants Rucaparib 600 mg BID for 21-day cycles	Rucaparib 600 mg BID (Part 2B) Rucaparib 600 mg BID for 21-day cycles	Rucaparib 160 mg QD (Part 1) Rucaparib 160 mg once a day (QD)	Rucaparib 300 mg QD (Part 1) Rucaparib 300 mg once a day (QD)	Rucaparib 500 mg QD (Part 1) Rucaparib 500 mg once a day (QD)	Rucaparib 240 mg BID (Part 1) Rucaparib 240 mg twice a day (BID)	Rucaparib 360 mg BID (Part 1) Rucaparib 360 mg twice a day (BID)	Rucaparib 480 mg BID (Part 1) Rucaparib 480 mg twice a day (BID)	Rucaparib 600 mg BID (Part 1) Rucaparib 600 mg twice a day (BID)	Rucaparib 840 mg BID (Part 1) Rucaparib 840 mg twice a day (BID)
Overall Survival (Part 2B)	764 Days Interval 166.0 to The upper confidence of the median is not reached due to not enough death events.	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Day -7 to Cycle 1 Day 1, or approximately 7 days

Population: A subset of patients treated with either 40 mg, 300 mg, or 600 mg rucaparib

Cmax = maximum concentration following administration of rucaparib. The effect of food on rucaparib PK parameters was assessed over a 24-hour period in blood samples from a subset of patients. Patients were given a single dose of 40 mg or 300 mg rucaparib (Part 1), or 600 mg rucaparib (Part 3) and were randomized to one of two sequences where they were either Fed (with a high-fat meal) or Fasted (without a high-fat meal) on Day -7 or Cycle 1 Day 1. On each day, patients underwent blood sampling for PK at the specified time points. The median Fed and Fasted Cmax values were calculated for each arm.

Outcome measures

Outcome measures
Measure	Rucaparib 600 mg BID (Part 2A) n=3 Participants Rucaparib 600 mg BID for 21-day cycles	Rucaparib 600 mg BID (Part 2B) n=6 Participants Rucaparib 600 mg BID for 21-day cycles	Rucaparib 160 mg QD (Part 1) n=26 Participants Rucaparib 160 mg once a day (QD)	Rucaparib 300 mg QD (Part 1) Rucaparib 300 mg once a day (QD)	Rucaparib 500 mg QD (Part 1) Rucaparib 500 mg once a day (QD)	Rucaparib 240 mg BID (Part 1) Rucaparib 240 mg twice a day (BID)	Rucaparib 360 mg BID (Part 1) Rucaparib 360 mg twice a day (BID)	Rucaparib 480 mg BID (Part 1) Rucaparib 480 mg twice a day (BID)	Rucaparib 600 mg BID (Part 1) Rucaparib 600 mg twice a day (BID)	Rucaparib 840 mg BID (Part 1) Rucaparib 840 mg twice a day (BID)
Food Effect on PK of Rucaparib - Cmax (Part 1 and Part 3) Cmax Fasted	57.6 ng/mL Interval 45.2 to 131.0	424 ng/mL Interval 182.0 to 638.0	585 ng/mL Interval 127.0 to 3100.0	—	—	—	—	—	—	—
Food Effect on PK of Rucaparib - Cmax (Part 1 and Part 3) Cmax Fed	71.1 ng/mL Interval 21.3 to 102.0	393 ng/mL Interval 177.0 to 1210.0	746 ng/mL Interval 198.0 to 2640.0	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Day -7 to Cycle 1 Day 1, or approximately 7 days

Population: A subset of patients treated with either 40 mg, 300 mg, or 600 mg rucaparib

Tmax = time to maximum concentration following administration of rucaparib. The effect of food on rucaparib PK parameters was assessed over a 24-hour period in blood samples from a subset of patients. Patients were given a single dose of 40 mg or 300 mg rucaparib (Part 1), or 600 mg rucaparib (Part 3) and were randomized to one of two sequences where they were either Fed (with a high-fat meal) or Fasted (without a high-fat meal) on Day -7 or Cycle 1 Day 1. On each day, patients underwent blood sampling for PK at the specified time points. The median Fed and Fasted Tmax values were calculated for each arm.

Outcome measures

Outcome measures
Measure	Rucaparib 600 mg BID (Part 2A) n=3 Participants Rucaparib 600 mg BID for 21-day cycles	Rucaparib 600 mg BID (Part 2B) n=6 Participants Rucaparib 600 mg BID for 21-day cycles	Rucaparib 160 mg QD (Part 1) n=26 Participants Rucaparib 160 mg once a day (QD)	Rucaparib 300 mg QD (Part 1) Rucaparib 300 mg once a day (QD)	Rucaparib 500 mg QD (Part 1) Rucaparib 500 mg once a day (QD)	Rucaparib 240 mg BID (Part 1) Rucaparib 240 mg twice a day (BID)	Rucaparib 360 mg BID (Part 1) Rucaparib 360 mg twice a day (BID)	Rucaparib 480 mg BID (Part 1) Rucaparib 480 mg twice a day (BID)	Rucaparib 600 mg BID (Part 1) Rucaparib 600 mg twice a day (BID)	Rucaparib 840 mg BID (Part 1) Rucaparib 840 mg twice a day (BID)
Food Effect on PK of Rucaparib - Tmax (Part 1 and Part 3) Tmax Fed	2.55 hr Interval 1.0 to 4.08	5.95 hr Interval 2.53 to 10.0	7.83 hr Interval 1.5 to 24.45	—	—	—	—	—	—	—
Food Effect on PK of Rucaparib - Tmax (Part 1 and Part 3) Tmax Fasted	4 hr Interval 2.5 to 4.05	4.09 hr Interval 2.5 to 24.22	4.02 hr Interval 0.53 to 24.83	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Day -7 to Cycle 1 Day 1, or approximately 7 days

Population: A subset of patients treated with either 40 mg, 300 mg, or 600 mg rucaparib. For the 40 mg and 300 mg arms, the number analyzed at Day 1 and Day 15 differs from the overall number based on number of evaluable samples collected at each time point.

AUC last = Area under the plasma concentration-time curve from time 0 to the last recorded observation. The effect of food on rucaparib PK parameters was assessed over a 24-hour period in blood samples from a subset of patients. Patients were given a single dose of 40 mg or 300 mg rucaparib (Part 1), or 600 mg rucaparib (Part 3) and were randomized to one of two sequences where they were either Fed (with a high-fat meal) or Fasted (without a high-fat meal) on Day -7 or Cycle 1 Day 1. On each day, patients underwent blood sampling for PK at the specified time points. The median Fed and Fasted AUC last values were calculated for each arm.

Outcome measures

Outcome measures
Measure	Rucaparib 600 mg BID (Part 2A) n=3 Participants Rucaparib 600 mg BID for 21-day cycles	Rucaparib 600 mg BID (Part 2B) n=6 Participants Rucaparib 600 mg BID for 21-day cycles	Rucaparib 160 mg QD (Part 1) n=26 Participants Rucaparib 160 mg once a day (QD)	Rucaparib 300 mg QD (Part 1) Rucaparib 300 mg once a day (QD)	Rucaparib 500 mg QD (Part 1) Rucaparib 500 mg once a day (QD)	Rucaparib 240 mg BID (Part 1) Rucaparib 240 mg twice a day (BID)	Rucaparib 360 mg BID (Part 1) Rucaparib 360 mg twice a day (BID)	Rucaparib 480 mg BID (Part 1) Rucaparib 480 mg twice a day (BID)	Rucaparib 600 mg BID (Part 1) Rucaparib 600 mg twice a day (BID)	Rucaparib 840 mg BID (Part 1) Rucaparib 840 mg twice a day (BID)
Food Effect on PK of Rucaparib - AUC Last (Part 1 and Part 3) AUC last Fasted	468 hr*ng/mL Interval 347.0 to 1410.0	5410 hr*ng/mL Interval 2390.0 to 8680.0	7050 hr*ng/mL Interval 1110.0 to 33000.0	—	—	—	—	—	—	—
Food Effect on PK of Rucaparib - AUC Last (Part 1 and Part 3) AUC last Fed	794 hr*ng/mL Interval 415.0 to 1170.0	6000 hr*ng/mL Interval 2670.0 to 12100.0	10900 hr*ng/mL Interval 1990.0 to 40400.0	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Screening to End of Treatment, up to approximately 15 months

Population: Safety population: Consist of all Part 1 patients who received at least one dose of rucaparib. One patient in the 40 mg dose group had no Baseline evaluation and was excluded from analyses of change from Baseline.

QTcF value change from baseline by daily dose corrected using Fridericia's method (QTcF). To evaluate the effects of rucaparib on the QT (interval from Q wave to T wave)/QTc (interval corrected for heart rate) interval, all patients underwent serial ECG monitoring at Screening, on Cycle 1 Day -1, Cycle 1 Day 1, Cycle 1 Day 15, Cycle 1 Day 22, on Day 1 of all subsequent cycles, at the EOT Visit, and as clinically indicated. Worst post-baseline QTcF value was used to categorize each patient.

Outcome measures

Outcome measures
Measure	Rucaparib 600 mg BID (Part 2A) n=5 Participants Rucaparib 600 mg BID for 21-day cycles	Rucaparib 600 mg BID (Part 2B) n=3 Participants Rucaparib 600 mg BID for 21-day cycles	Rucaparib 160 mg QD (Part 1) n=4 Participants Rucaparib 160 mg once a day (QD)	Rucaparib 300 mg QD (Part 1) n=9 Participants Rucaparib 300 mg once a day (QD)	Rucaparib 500 mg QD (Part 1) n=4 Participants Rucaparib 500 mg once a day (QD)	Rucaparib 240 mg BID (Part 1) n=3 Participants Rucaparib 240 mg twice a day (BID)	Rucaparib 360 mg BID (Part 1) n=8 Participants Rucaparib 360 mg twice a day (BID)	Rucaparib 480 mg BID (Part 1) n=9 Participants Rucaparib 480 mg twice a day (BID)	Rucaparib 600 mg BID (Part 1) n=7 Participants Rucaparib 600 mg twice a day (BID)	Rucaparib 840 mg BID (Part 1) n=3 Participants Rucaparib 840 mg twice a day (BID)
QTcF Value Change From Baseline (Part 1) QTcF Change from Baseline ≥60 msec	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
QTcF Value Change From Baseline (Part 1) QTcF Change from Baseline <30 msec	5 Participants	3 Participants	4 Participants	9 Participants	3 Participants	3 Participants	8 Participants	9 Participants	7 Participants	3 Participants
QTcF Value Change From Baseline (Part 1) QTcF Change from Baseline ≥30 to <60 msec	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

Adverse Events

Rucaparib 40 mg QD (Part 1)

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Rucaparib 80 mg QD (Part 1)

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Rucaparib 160 mg QD (Part 1)

Serious events: 3 serious events

Other events: 4 other events

Deaths: 1 deaths

Rucaparib 300 mg QD (Part 1)

Serious events: 4 serious events

Other events: 9 other events

Deaths: 1 deaths

Rucaparib 500 mg QD (Part 1)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Rucaparib 240 mg BID (Part 1)

Serious events: 2 serious events

Other events: 3 other events

Deaths: 1 deaths

Rucaparib 360 mg BID (Part 1)

Serious events: 3 serious events

Other events: 8 other events

Deaths: 0 deaths

Rucaparib 480 mg BID (Part 1)

Serious events: 4 serious events

Other events: 8 other events

Deaths: 1 deaths

Rucaparib 600 mg BID (Part 1)

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Rucaparib 840 mg BID (Part 1)

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Rucaparib 600 mg BID (Part 2A)

Serious events: 19 serious events

Other events: 41 other events

Deaths: 4 deaths

Rucaparib 600 mg BID (Part 2B)

Serious events: 3 serious events

Other events: 12 other events

Deaths: 1 deaths

Rucaparib 600 mg BID (Part 3)

Serious events: 9 serious events

Other events: 26 other events

Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure	Rucaparib 40 mg QD (Part 1) n=6 participants at risk Rucaparib 40 mg QD for 21-day cycles	Rucaparib 80 mg QD (Part 1) n=3 participants at risk Rucaparib 80 mg QD for 21-day cycles	Rucaparib 160 mg QD (Part 1) n=4 participants at risk Rucaparib 160 mg QD for 21-day cycles	Rucaparib 300 mg QD (Part 1) n=9 participants at risk Rucaparib 300 mg QD for 21-day cycles	Rucaparib 500 mg QD (Part 1) n=4 participants at risk Rucaparib 500 mg QD for 21-day cycles	Rucaparib 240 mg BID (Part 1) n=3 participants at risk Rucaparib 240 mg BID for 21-day cycles	Rucaparib 360 mg BID (Part 1) n=8 participants at risk Rucaparib 360 mg BID for 21-day cycles	Rucaparib 480 mg BID (Part 1) n=9 participants at risk Rucaparib 480 mg BID for 21-day cycles	Rucaparib 600 mg BID (Part 1) n=7 participants at risk Rucaparib 600 mg BID for 21-day cycles	Rucaparib 840 mg BID (Part 1) n=3 participants at risk Rucaparib 840 mg BID for 21-day cycles	Rucaparib 600 mg BID (Part 2A) n=42 participants at risk Rucaparib 600 mg BID for 21-day cycles	Rucaparib 600 mg BID (Part 2B) n=12 participants at risk Rucaparib 600 mg BID for 21-day cycles	Rucaparib 600 mg BID (Part 3) n=26 participants at risk Rucaparib 600 mg BID for 21-day cycles
Blood and lymphatic system disorders Anaemia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.1% 3/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Blood and lymphatic system disorders Neutropenia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Cardiac disorders Atrial fibrillation	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Abdominal pain	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Ascites	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Constipation	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Haematemesis	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	4.8% 2/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Large intestinal obstruction	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Nausea	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 2/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Obstruction gastric	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Pancreatitis	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Small intestinal obstruction	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.1% 3/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Vomiting	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
General disorders Generalised oedema	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
General disorders Non-cardiac chest pain	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
General disorders Pyrexia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Cellulitis	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Cytomegalovirus infection	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Diverticulitis	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Epiglottiis	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Influenza	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Lower respiratory tract infection	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Pneumonia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	4.8% 2/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Sepsis	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Urinary tract infection	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Injury, poisoning and procedural complications Radius fracture	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Injury, poisoning and procedural complications Urinary tract stoma complication	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Metabolism and nutrition disorders Hyponatraemia	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B-cell type acute leukaemia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	22.2% 2/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	66.7% 2/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	9.5% 4/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.5% 3/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myodysplastic syndrome	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.7% 2/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Nervous system disorders Cerebrovascular accident	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Nervous system disorders Headache	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Nervous system disorders Seizure	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Renal and urinary disorders Acute kidney injury	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Reproductive system and breast disorders Vaginal fistula	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.

Other adverse events

Other adverse events
Measure	Rucaparib 40 mg QD (Part 1) n=6 participants at risk Rucaparib 40 mg QD for 21-day cycles	Rucaparib 80 mg QD (Part 1) n=3 participants at risk Rucaparib 80 mg QD for 21-day cycles	Rucaparib 160 mg QD (Part 1) n=4 participants at risk Rucaparib 160 mg QD for 21-day cycles	Rucaparib 300 mg QD (Part 1) n=9 participants at risk Rucaparib 300 mg QD for 21-day cycles	Rucaparib 500 mg QD (Part 1) n=4 participants at risk Rucaparib 500 mg QD for 21-day cycles	Rucaparib 240 mg BID (Part 1) n=3 participants at risk Rucaparib 240 mg BID for 21-day cycles	Rucaparib 360 mg BID (Part 1) n=8 participants at risk Rucaparib 360 mg BID for 21-day cycles	Rucaparib 480 mg BID (Part 1) n=9 participants at risk Rucaparib 480 mg BID for 21-day cycles	Rucaparib 600 mg BID (Part 1) n=7 participants at risk Rucaparib 600 mg BID for 21-day cycles	Rucaparib 840 mg BID (Part 1) n=3 participants at risk Rucaparib 840 mg BID for 21-day cycles	Rucaparib 600 mg BID (Part 2A) n=42 participants at risk Rucaparib 600 mg BID for 21-day cycles	Rucaparib 600 mg BID (Part 2B) n=12 participants at risk Rucaparib 600 mg BID for 21-day cycles	Rucaparib 600 mg BID (Part 3) n=26 participants at risk Rucaparib 600 mg BID for 21-day cycles
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
General disorders Chest pain	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Skin and subcutaneous tissue disorders Acne	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Nervous system disorders Tremor	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.1% 3/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Psychiatric disorders Agitation	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Psychiatric disorders Anxiety	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 2/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 6/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.7% 2/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Skin and subcutaneous tissue disorders Hypertrichosis	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Investigations Weight decreased	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	19.0% 8/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Psychiatric disorders Depressed mood	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	16.7% 2/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Investigations White blood cell count decreased	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 3/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.9% 5/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Skin and subcutaneous tissue disorders Night sweats	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Skin and subcutaneous tissue disorders Onychomadesis	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Skin and subcutaneous tissue disorders Rash papular	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Skin and subcutaneous tissue disorders Skin hypopigmentation	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Skin and subcutaneous tissue disorders Telangiectasia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Vascular disorders Flushing	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Vascular disorders Hypotension	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Vascular disorders Thrombosis	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Psychiatric disorders Depression	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	9.5% 4/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Renal and urinary disorders Dysuria	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 2/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.1% 3/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.7% 2/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Psychiatric disorders Insomnia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	44.4% 4/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 6/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.7% 2/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Blood and lymphatic system disorders Anaemia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 3/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	50.0% 4/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 3/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	57.1% 4/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	71.4% 30/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	66.7% 8/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	23.1% 6/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Blood and lymphatic system disorders Leukopenia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.1% 3/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Blood and lymphatic system disorders Lymphopenia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	16.7% 2/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Blood and lymphatic system disorders Neutropenia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	22.2% 2/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	28.6% 2/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	21.4% 9/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	16.7% 2/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.5% 3/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	42.9% 3/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	19.0% 8/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 4/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.5% 3/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Cardiac disorders Tachycardia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	37.5% 3/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Ear and labyrinth disorders Ear pain	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	4.8% 2/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	16.7% 2/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Eye disorders Conjunctival hyperaemia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Eye disorders Vision blurred	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.1% 3/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.7% 2/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Abdominal distension	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 2/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	22.2% 2/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	26.2% 11/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	15.4% 4/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Abdominal pain	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	55.6% 5/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 2/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 3/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	47.6% 20/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	41.7% 5/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	15.4% 4/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Abdominal pain lower	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 6/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	16.7% 2/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Abdominal pain upper	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 2/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.9% 5/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	16.7% 2/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Aphthous ulcer	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	16.7% 2/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Ascites	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	22.2% 2/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Constipation	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	50.0% 2/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	55.6% 5/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	37.5% 3/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	22.2% 2/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	52.4% 22/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	58.3% 7/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	26.9% 7/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Diarrhoea	33.3% 2/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	22.2% 2/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	22.2% 2/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	28.6% 2/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	100.0% 3/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	40.5% 17/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 3/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	15.4% 4/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Dry mouth	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	22.2% 2/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.1% 3/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.7% 2/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Dyspepsia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	22.2% 2/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 2/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.1% 3/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	16.7% 2/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	23.1% 6/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Flatulence	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.9% 5/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	22.2% 2/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	4.8% 2/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	16.7% 2/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.7% 2/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Mouth ulceration	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Nausea	50.0% 3/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	75.0% 3/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	66.7% 6/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	75.0% 6/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	44.4% 4/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	57.1% 4/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	100.0% 3/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	83.3% 35/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	91.7% 11/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	42.3% 11/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Stomatitis	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	16.7% 7/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Tooth disorder	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Vomiting	33.3% 2/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	75.0% 3/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	44.4% 4/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	37.5% 3/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	55.6% 5/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	57.1% 4/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	66.7% 2/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	57.1% 24/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	75.0% 9/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	34.6% 9/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
General disorders Asthenia	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	31.0% 13/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.7% 2/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
General disorders Axillary pain	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
General disorders Chills	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.9% 5/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
General disorders Early satiety	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.1% 3/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
General disorders Fatigue	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	66.7% 6/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	50.0% 2/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	75.0% 6/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	55.6% 5/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	71.4% 5/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	71.4% 30/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	50.0% 6/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	53.8% 14/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
General disorders Influenza like illness	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.9% 5/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
General disorders Injection site bruising	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
General disorders Malaise	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
General disorders Mucosal inflammation	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	22.2% 2/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	4.8% 2/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.7% 2/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
General disorders Non-cardiac chest pain	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
General disorders Oedema peripheral	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 3/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	9.5% 4/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	19.2% 5/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
General disorders Peripheral swelling	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.1% 3/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.7% 2/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
General disorders Pyrexia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 3/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	37.5% 3/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.9% 5/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 3/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.5% 3/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Immune system disorders Allergy to arthropod bite	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Ear infection	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	16.7% 2/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Gastroenteritis	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	4.8% 2/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Gingivitis	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Herpes simplex	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Lower respiratory tract infection	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 4/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Pneumonia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.1% 3/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Tooth infection	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Upper respiratory tract infection	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	28.6% 12/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	16.7% 2/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.7% 2/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Urinary tract infection	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 2/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	42.9% 3/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	19.0% 8/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 3/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	19.2% 5/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Viral upper respiratory infection	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.7% 2/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Injury, poisoning and procedural complications Limb injury	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Investigations Alanine aminotransferase increased	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	22.2% 2/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	71.4% 5/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	57.1% 24/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	16.7% 2/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	23.1% 6/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Investigations Aspartate aminotransferase increased	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	22.2% 2/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 3/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	71.4% 5/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	52.4% 22/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	16.7% 2/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	23.1% 6/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Investigations Blood alkaline phosphatase increased	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	22.2% 2/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	22.2% 2/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	57.1% 4/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	23.8% 10/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Investigations Blood bilirubin increased	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.1% 3/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Investigations Blood cholesterol increased	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 3/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.1% 3/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	16.7% 2/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.5% 3/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Investigations Blood creatinine increased	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	35.7% 15/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	50.0% 6/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.5% 3/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Investigations Blood potassium increased	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Investigations Blood urea increased	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.1% 3/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Investigations Gamma-glutamyltransferase increased	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	4.8% 2/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Investigations Lymphocyte count decreased	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Investigations Neutrophil count decreased	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 3/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.1% 3/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.5% 3/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Investigations Platelet count decreased	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	42.9% 3/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	16.7% 7/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	16.7% 2/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.7% 2/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Investigations Transaminases increased	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	4.8% 2/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.7% 2/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Metabolism and nutrition disorders Decreased appetite	50.0% 3/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	66.7% 6/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	66.7% 2/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	37.5% 3/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	28.6% 12/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 3/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	38.5% 10/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Metabolism and nutrition disorders Dehydration	33.3% 2/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	28.6% 2/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.1% 3/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.7% 2/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Metabolism and nutrition disorders Hypercholesterolaemia	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	9.5% 4/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Metabolism and nutrition disorders Hyperglycaemia	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	22.2% 2/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	22.2% 2/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.7% 2/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Metabolism and nutrition disorders Hypertriglyceridaemia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.7% 2/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Metabolism and nutrition disorders Hypoalbuminaemia	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	4.8% 2/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Metabolism and nutrition disorders Hypokalaemia	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	9.5% 4/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	22.2% 2/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	16.7% 7/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.9% 5/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	16.7% 2/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 2/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.1% 3/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Musculoskeletal and connective tissue disorders Arthralgia	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	21.4% 9/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 3/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.5% 3/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	22.2% 2/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	16.7% 7/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	16.7% 2/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	15.4% 4/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.1% 3/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Musculoskeletal and connective tissue disorders Joint swelling	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.1% 3/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	16.7% 2/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.5% 3/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	4.8% 2/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 2/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	4.8% 2/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.1% 3/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	22.2% 2/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.9% 5/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.7% 2/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	4.8% 2/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Nervous system disorders Dizziness	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 2/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	22.2% 2/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	28.6% 2/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	21.4% 9/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	23.1% 6/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Nervous system disorders Dysgeusia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 2/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	66.7% 2/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	40.5% 17/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	16.7% 2/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	19.2% 5/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Nervous system disorders Headache	33.3% 2/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	22.2% 2/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 2/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	28.6% 2/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	47.6% 20/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	16.7% 2/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.7% 2/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Nervous system disorders Lethargy	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 3/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Nervous system disorders Neuropathy peripheral	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	66.7% 2/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Nervous system disorders Paraesthesia	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	4.8% 2/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Nervous system disorders Restless legs syndrome	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Renal and urinary disorders Micturition urgency	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Renal and urinary disorders Proteinuria	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.1% 3/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Renal and urinary disorders Urinary incontinence	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.1% 3/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Reproductive system and breast disorders Pelvic pain	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.9% 5/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Reproductive system and breast disorders Vaginal discharge	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Reproductive system and breast disorders Vaginal haemorrhage	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	4.8% 2/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	22.2% 2/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 3/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	28.6% 2/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	66.7% 2/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	23.8% 10/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	16.7% 2/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	15.4% 4/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	22.2% 2/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	37.5% 3/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 3/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	26.2% 11/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	15.4% 4/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.1% 3/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.5% 3/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.1% 3/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Respiratory, thoracic and mediastinal disorders Nasal discomfort	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	22.2% 2/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	16.7% 7/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	22.2% 2/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	4.8% 2/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	19.0% 8/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Skin and subcutaneous tissue disorders Blister	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 6/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.7% 2/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	4.8% 2/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Skin and subcutaneous tissue disorders Nail discolouration	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.1% 3/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Skin and subcutaneous tissue disorders Photosensitivity reaction	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	22.2% 2/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	22.2% 2/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.9% 5/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 6/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.5% 3/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Skin and subcutaneous tissue disorders Rash	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	22.2% 2/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	19.0% 8/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.5% 3/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Skin and subcutaneous tissue disorders Rash macular	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	7.1% 3/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Skin and subcutaneous tissue disorders Skin lesion	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Vascular disorders Hot flush	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	4.8% 2/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	16.7% 2/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Vascular disorders Hypertension	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	9.5% 4/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	16.7% 2/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Vascular disorders Lymphoedema	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	16.7% 2/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Nasopharyngitis	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.9% 5/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Renal and urinary disorders Pollakiuria	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	8.3% 1/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Blood and lymphatic system disorders Splenomegaly	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Cardiac disorders Bradycardia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	4.8% 2/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Cardiac disorders Palpitations	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 2/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Ear and labyrinth disorders Ear congestion	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Eye disorders Macular degeneration	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Eye disorders Mydriasis	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Eye disorders Visual acuity reduced	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Eye disorders Visual impairment	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Anal pruritus	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Haemorrhoids	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Odynophagia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Oral pain	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	4.8% 2/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Tongue ulceration	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Tooth erosion	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Gastrointestinal disorders Toothache	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
General disorders Catheter site inflammation	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
General disorders Catheter site pain	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
General disorders Chest discomfort	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
General disorders Gait disturbance	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
General disorders Local swelling	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
General disorders Nodule	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
General disorders Pain	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	4.8% 2/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
General disorders Suprapubic pain	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
General disorders Ulcer	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Hepatobiliary disorders Hepatomegaly	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Hepatobiliary disorders Portal vein thrombosis	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Immune system disorders Anaphylactic reaction	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Immune system disorders Hypersensitivity	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Conjunctivitis	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	4.8% 2/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Furuncle	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Nervous system disorders Balance disorder	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Gastroenteritis viral	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Herpes virus infection	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Influenza	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	4.8% 2/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Oral herpes	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Oral infection	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Pharyngitis	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Respiratory tract infection	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Rhinitis	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	4.8% 2/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Skin candida	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Skin infection	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Staphylococcal infection	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	22.2% 2/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Urinary tract infection enterococcal	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Infections and infestations Wound infection	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Injury, poisoning and procedural complications Contusion	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Injury, poisoning and procedural complications Fall	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	4.8% 2/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Injury, poisoning and procedural complications Procedural pain	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Injury, poisoning and procedural complications Wound	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Investigations Blood magnesium decreased	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Investigations Blood phosphorus decreased	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Investigations Blood urea nitrogen/creatinine ratio increased	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Investigations Breath sounds abnormal	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Investigations Heart rate increased	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Investigations Neutrophil count increased	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Metabolism and nutrition disorders Hyperphosphataemia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	4.8% 2/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Musculoskeletal and connective tissue disorders Bone lesion	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Musculoskeletal and connective tissue disorders Extremity contracture	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Musculoskeletal and connective tissue disorders Groin pain	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Musculoskeletal and connective tissue disorders Joint stiffness	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	14.3% 1/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Musculoskeletal and connective tissue disorders Musculoskeletal discomfort	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Musculoskeletal and connective tissue disorders Pain in jaw	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Musculoskeletal and connective tissue disorders Temporomandibular joint syndrome	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Nervous system disorders Memory impairment	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	4.8% 2/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Nervous system disorders Seizure	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	3.8% 1/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Nervous system disorders Sensory loss	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Psychiatric disorders Mental fatigue	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	12.5% 1/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Psychiatric disorders Mental status changes	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Renal and urinary disorders Hydronephrosis	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Renal and urinary disorders Obstructive uropathy	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Renal and urinary disorders Renal colic	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Reproductive system and breast disorders Breast pain	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	2.4% 1/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Reproductive system and breast disorders Pruritus genital	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	33.3% 1/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Reproductive system and breast disorders Vaginal fistula	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Reproductive system and breast disorders Vulvovaginal discomfort	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	25.0% 1/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Reproductive system and breast disorders Vulvovaginal pain	16.7% 1/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Respiratory, thoracic and mediastinal disorders Catarrh	0.00% 0/6 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	11.1% 1/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/4 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/8 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/9 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/7 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/3 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/42 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/12 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.	0.00% 0/26 • Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.

Additional Information

Medical Information Department

Clovis Oncology, Inc.

Phone: +1 415 409 7220

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor's agreements with investigators require proposed public disclosures of trial results to be submitted to Sponsor for review prior to publication. Sponsor may request deletion of confidential information or a delay in publication to address intellectual property concerns, but Sponsor may not suppress publication of the trial results indefinitely. Sponsor may request delay of a single-center publication until after the release of a multi-site publication or an agreed upon period of time.
Publication restrictions are in place

Restriction type: OTHER