Trial Outcomes & Findings for A Study of the Safety, Tolerability, and Efficacy of Epacadostat Administered in Combination With Nivolumab in Select Advanced Cancers (ECHO-204) (NCT NCT02327078)

Last Updated: 2025-08-14

Results Overview

A DLT was defined as occurrence of any treatment-emergent adverse event (TEAE) in Phase 1 Parts 1 and 2. DLT included all TEAE of specified grades such as 1) Hematologic toxicities - any Grade 4 thrombocytopenia or neutropenia, anemia, febrile neutropenia, ≥ Grade 3 hemolysis, thrombocytopenia and 2) Nonhematologic toxicities - Grade 4 AE, nausea, vomiting, or diarrhea, electrolyte abnormality, ≥ Grade 3 aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin elevation, Grade 2 AST/ALT with symptomatic liver inflammation, AST or ALT \> 3 × upper limit of normal (ULN) and concurrent total bilirubin \> 2 × ULN without initial findings of cholestasis, and any other ≥ Grade 3 toxicity. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and up to 100 days after last dose of study drug.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

307 participants

Primary outcome timeframe

Day 42

Results posted on

2025-08-14

Participant Flow

Participants took part in 22 study sites in the United States and 2 study sites in the United Kingdom from 26 November 2014 to 16 June 2020.

A total of 307 participants were enrolled in this study, 48 participants were enrolled in Phase 1 and 259 participants were enrolled in Phase 2. Participants in Phase 1 Part 2 and Phase 2 received dose per select solid tumor types (Colorectal, Melanoma I/O Naïve, Melanoma I/O relapsed, Melanoma I/O refractory, Non-small cell lung cancer (NSCLC), Ovarian, Squamous cell carcinoma of the head and neck (SCCHN), Diffuse large B-cell lymphoma (DLBCL) and Glioblastoma).

Participant milestones

Participant milestones
Measure	Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg Participants received epacadostat 25 mg, orally, twice daily (BID) in combination of nivolumab 3 mg/kg intravenously (IV), on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg Participants received epacadostat 50 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, once every 3 weeks (Q3W), on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg Participants received epacadostat 100 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 300 mg + Nivolumab 3 mg Participants received epacadostat 300 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + 5-FU/Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, once every 2 weeks (Q2W), on Day 1 of each 21-day cycle along with 5-FU/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Pemetrexed/ Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Pemetrexed /Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Paclitaxel/ Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Paclitaxel/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 2: Epacadostat 100 mg + Nivolumab 240/480 mg Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 and participants with melanoma I/O-relapsed and melanoma I/O-refractory enrolled in this arm received epacadostat 100 mg BID in combination with nivolumab 480 mg IV infusion once every 4 weeks (Q4W) on Days 1 and Day 29 of each 8-week cycle.	Phase 2: Epacadostat 300 mg + Nivolumab 240 mg Participants with select solid tumor types received epacadostat 300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle.
Overall Study STARTED	3	6	14	13	6	3	3	83	176
Overall Study COMPLETED	0	0	0	0	0	0	0	0	0
Overall Study NOT COMPLETED	3	6	14	13	6	3	3	83	176

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg Participants received epacadostat 25 mg, orally, twice daily (BID) in combination of nivolumab 3 mg/kg intravenously (IV), on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg Participants received epacadostat 50 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, once every 3 weeks (Q3W), on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg Participants received epacadostat 100 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 300 mg + Nivolumab 3 mg Participants received epacadostat 300 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + 5-FU/Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, once every 2 weeks (Q2W), on Day 1 of each 21-day cycle along with 5-FU/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Pemetrexed/ Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Pemetrexed /Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Paclitaxel/ Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Paclitaxel/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 2: Epacadostat 100 mg + Nivolumab 240/480 mg Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 and participants with melanoma I/O-relapsed and melanoma I/O-refractory enrolled in this arm received epacadostat 100 mg BID in combination with nivolumab 480 mg IV infusion once every 4 weeks (Q4W) on Days 1 and Day 29 of each 8-week cycle.	Phase 2: Epacadostat 300 mg + Nivolumab 240 mg Participants with select solid tumor types received epacadostat 300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle.
Overall Study Participants Decision: Consent Withdrawal from Study and Follow-up	0	1	2	1	1	0	0	11	25
Overall Study Death	2	4	10	6	4	3	2	51	97
Overall Study Lost to Follow-up	0	1	1	0	0	0	0	2	5
Overall Study Site Terminated by Sponsor	1	0	1	4	0	0	0	11	25
Overall Study Physician Decision	0	0	0	1	0	0	0	0	1
Overall Study Completed 100 Day Safety Follow-up Period	0	0	0	1	1	0	1	3	11
Overall Study Reason not Specified	0	0	0	0	0	0	0	5	12

Baseline Characteristics

A Study of the Safety, Tolerability, and Efficacy of Epacadostat Administered in Combination With Nivolumab in Select Advanced Cancers (ECHO-204)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg n=3 Participants Participants received epacadostat 25 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg n=6 Participants Participants received epacadostat 50 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg n=14 Participants Participants received epacadostat 100 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 300 mg + Nivolumab 3 mg n=13 Participants Participants received epacadostat 300 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + 5-FU/Platinum n=6 Participants Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with 5-FU/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Pemetrexed/ Platinum n=3 Participants Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Pemetrexed /Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Paclitaxel/ Platinum n=3 Participants Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Paclitaxel/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 2: Epacadostat 100 mg + Nivolumab 240/480 mg n=83 Participants Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 and participants with melanoma I/O-relapsed and melanoma I/O-refractory enrolled in this arm received epacadostat 100 mg BID in combination with nivolumab 480 mg IV infusion Q4W on Days 1 and Day 29 of each 8-week cycle.	Phase 2: Epacadostat 300 mg + Nivolumab 240 mg n=176 Participants Participants with select solid tumor types received epacadostat 300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle.	Total n=307 Participants Total of all reporting groups
Age, Continuous	50.0 years STANDARD_DEVIATION 26.00 • n=5 Participants	62.5 years STANDARD_DEVIATION 12.41 • n=7 Participants	57.5 years STANDARD_DEVIATION 13.27 • n=5 Participants	61.6 years STANDARD_DEVIATION 10.67 • n=4 Participants	64.3 years STANDARD_DEVIATION 6.38 • n=21 Participants	67.7 years STANDARD_DEVIATION 6.43 • n=10 Participants	70.3 years STANDARD_DEVIATION 11.37 • n=115 Participants	56.7 years STANDARD_DEVIATION 13.82 • n=24 Participants	62.6 years STANDARD_DEVIATION 12.12 • n=42 Participants	60.7 years STANDARD_DEVIATION 12.33 • n=42 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	1 Participants n=7 Participants	11 Participants n=5 Participants	5 Participants n=4 Participants	1 Participants n=21 Participants	1 Participants n=10 Participants	1 Participants n=115 Participants	46 Participants n=24 Participants	77 Participants n=42 Participants	145 Participants n=42 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	5 Participants n=7 Participants	3 Participants n=5 Participants	8 Participants n=4 Participants	5 Participants n=21 Participants	2 Participants n=10 Participants	2 Participants n=115 Participants	37 Participants n=24 Participants	99 Participants n=42 Participants	162 Participants n=42 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	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	6 Participants n=24 Participants	11 Participants n=42 Participants	17 Participants n=42 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	5 Participants n=7 Participants	14 Participants n=5 Participants	13 Participants n=4 Participants	6 Participants n=21 Participants	3 Participants n=10 Participants	3 Participants n=115 Participants	77 Participants n=24 Participants	159 Participants n=42 Participants	283 Participants n=42 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 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	6 Participants n=42 Participants	7 Participants n=42 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
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	0 Participants n=115 Participants	0 Participants n=24 Participants	3 Participants n=42 Participants	3 Participants n=42 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	1 Participants n=42 Participants	1 Participants n=42 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	2 Participants n=24 Participants	4 Participants n=42 Participants	7 Participants n=42 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants	13 Participants n=4 Participants	5 Participants n=21 Participants	3 Participants n=10 Participants	3 Participants n=115 Participants	76 Participants n=24 Participants	160 Participants n=42 Participants	282 Participants n=42 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
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	5 Participants n=24 Participants	8 Participants n=42 Participants	14 Participants n=42 Participants

PRIMARY outcome

Timeframe: Day 42

Population: The Phase 1, Part 1 Safety Population includes all participants enrolled in the study who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg n=3 Participants Participants received epacadostat 25 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg n=6 Participants Participants received epacadostat 50 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg n=14 Participants Participants received epacadostat 100 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 300 mg + Nivolumab 3 mg n=13 Participants Participants received epacadostat 300 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + 5-FU/Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with 5-FU/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Pemetrexed/ Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Pemetrexed /Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Paclitaxel/ Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Paclitaxel/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in SCCHN Participants with SCCHN received epacadostat 100/300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in Glioblastoma Participants with Glioblastoma received epacadostat 100/300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle.
Phase 1, Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—

PRIMARY outcome

Timeframe: Day 42

Population: The Phase 1, Part 2 Safety Population includes all participants enrolled in the study who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg n=6 Participants Participants received epacadostat 25 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg n=3 Participants Participants received epacadostat 50 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg n=3 Participants Participants received epacadostat 100 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 300 mg + Nivolumab 3 mg Participants received epacadostat 300 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + 5-FU/Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with 5-FU/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Pemetrexed/ Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Pemetrexed /Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Paclitaxel/ Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Paclitaxel/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in SCCHN Participants with SCCHN received epacadostat 100/300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in Glioblastoma Participants with Glioblastoma received epacadostat 100/300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle.
Phase 1, Part 2: Number of Participants With Dose Limiting Toxicities (DLTs)	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—

PRIMARY outcome

Timeframe: up to approximately 39 months

Population: The Phase 1, Parts 1 and 2 Safety Population includes all participants enrolled in the study who received at least 1 dose of study drug.

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and up to 100 days after last dose of study drug.

Outcome measures

Outcome measures
Measure	Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg n=3 Participants Participants received epacadostat 25 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg n=6 Participants Participants received epacadostat 50 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg n=14 Participants Participants received epacadostat 100 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 300 mg + Nivolumab 3 mg n=13 Participants Participants received epacadostat 300 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + 5-FU/Platinum n=6 Participants Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with 5-FU/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Pemetrexed/ Platinum n=3 Participants Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Pemetrexed /Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Paclitaxel/ Platinum n=3 Participants Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Paclitaxel/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in SCCHN Participants with SCCHN received epacadostat 100/300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in Glioblastoma Participants with Glioblastoma received epacadostat 100/300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle.
Phase 1, Parts 1 and 2: Number of Participants With At Least One Treatment-Emergent Adverse Event (TEAE)	3 Participants	6 Participants	14 Participants	13 Participants	6 Participants	3 Participants	3 Participants	—	—

PRIMARY outcome

Timeframe: From first dose up end of the study (up to approximately 6 years)

ORR was defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigator assessment of radiographic disease per RECIST v1.1. CR per RECIST v 1.1 was defined as disappearance of all target lesions. PR per RECIST v 1.1 was defined as At least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the Baseline sum diameters. Data is reported as per dose received by the participants with a particular cancer type. CR per Cheson criteria was defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms. PR per Cheson criteria was defined as at least a 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses.

Outcome measures

Outcome measures
Measure	Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg n=26 Participants Participants received epacadostat 25 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg n=18 Participants Participants received epacadostat 50 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg n=50 Participants Participants received epacadostat 100 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 300 mg + Nivolumab 3 mg n=7 Participants Participants received epacadostat 300 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + 5-FU/Platinum n=7 Participants Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with 5-FU/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Pemetrexed/ Platinum n=58 Participants Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Pemetrexed /Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Paclitaxel/ Platinum n=29 Participants Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Paclitaxel/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in SCCHN n=31 Participants Participants with SCCHN received epacadostat 100/300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in Glioblastoma n=33 Participants Participants with Glioblastoma received epacadostat 100/300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle.
Phase 2: Objective Response Rate (ORR) in Participants With Select Solid Tumors Per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 for Participants With Solid Tumors and Per Cheson Criteria for Participants With DLBCL	3.8 percentage of participants	0.0 percentage of participants	62.0 percentage of participants	28.6 percentage of participants	28.6 percentage of participants	20.7 percentage of participants	13.8 percentage of participants	25.8 percentage of participants	0.0 percentage of participants

PRIMARY outcome

Timeframe: From first dose up end of the study (up to approximately 6 years)

Population: The Phase 2 Full Analysis Population includes all participants enrolled in the study who take at least 1 dose of study drug. The data is reported per cancer type in this outcome measure.

PFS is defined as the time from randomization to the first documented progressive disease per RECIST v1.1 or death due to any cause, whichever occurs first.

Outcome measures

Outcome measures
Measure	Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg n=26 Participants Participants received epacadostat 25 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg n=18 Participants Participants received epacadostat 50 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg n=50 Participants Participants received epacadostat 100 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 300 mg + Nivolumab 3 mg n=7 Participants Participants received epacadostat 300 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + 5-FU/Platinum n=7 Participants Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with 5-FU/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Pemetrexed/ Platinum n=58 Participants Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Pemetrexed /Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Paclitaxel/ Platinum n=29 Participants Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Paclitaxel/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in SCCHN n=31 Participants Participants with SCCHN received epacadostat 100/300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in Glioblastoma n=33 Participants Participants with Glioblastoma received epacadostat 100/300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle.
Phase 2: Progression Free Survival (PFS)	1.78 months Interval 1.74 to 1.81	1.64 months Interval 1.35 to 3.52	NA months Interval 9.51 to Median and upper limit of 95% confidence interval (CI) was not estimable due to low number of participants with events.	1.76 months Interval 0.46 to Upper limit of 95% CI was not estimable due to low number of participants with events.	2.55 months Interval 0.59 to Upper limit of 95% CI was not estimable due to low number of participants with events.	1.88 months Interval 1.78 to 2.04	1.88 months Interval 1.68 to 3.52	3.62 months Interval 1.78 to 9.08	1.84 months Interval 1.78 to 2.63

PRIMARY outcome

Timeframe: Month 9

Population: The Phase 2 Full Analysis Population includes all participants enrolled in the study who take at least 1 dose of study drug. The data is reported for participants with Glioblastoma cancer type for this outcome measure.

OS rate is defined as the proportion of participants alive 9 months after the start of treatment.

Outcome measures

Outcome measures
Measure	Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg n=33 Participants Participants received epacadostat 25 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg Participants received epacadostat 50 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg Participants received epacadostat 100 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 300 mg + Nivolumab 3 mg Participants received epacadostat 300 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + 5-FU/Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with 5-FU/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Pemetrexed/ Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Pemetrexed /Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Paclitaxel/ Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Paclitaxel/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in SCCHN Participants with SCCHN received epacadostat 100/300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in Glioblastoma Participants with Glioblastoma received epacadostat 100/300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle.
Phase 2: Overall Survival (OS) Rate of Proportion With Glioblastoma	0.458 proportion of participants Interval 0.297 to 0.605	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From first dose up end of the study (up to approximately 6 years)

Population: The Phase 1, Part 2 Full Analysis Population includes all participants enrolled in the study who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg n=6 Participants Participants received epacadostat 25 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg n=3 Participants Participants received epacadostat 50 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg n=3 Participants Participants received epacadostat 100 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 300 mg + Nivolumab 3 mg Participants received epacadostat 300 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + 5-FU/Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with 5-FU/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Pemetrexed/ Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Pemetrexed /Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Paclitaxel/ Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Paclitaxel/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in SCCHN Participants with SCCHN received epacadostat 100/300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in Glioblastoma Participants with Glioblastoma received epacadostat 100/300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle.
Phase 1, Part 2: ORR Per RECIST v1.1 and for Participants With Advanced or Metastatic SCCHN and Advanced or Metastatic NSCLC	50.0 percentage of participants	33.3 percentage of participants	100.0 percentage of participants	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From first dose up end of the study (up to approximately 6 years)

Population: The Phase 1, Part 1 Full Analysis Population includes all participants enrolled in the study who received at least 1 dose of study drug.

ORR was defined as percentage of participants having CR or PR as determined by investigator assessment of radiographic disease per RECIST v1.1. CR per RECIST v 1.1 was defined as disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the Baseline sum diameters. Per Cheson criteria, CR: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms. PR: at least a 50% decrease in SPD of up to 6 of the largest dominant nodes or nodal masses. Per RANO criteria, CR: Complete disappearance of all enhancing measurable and non-measurable disease sustained. PR: at least ≥50% decrease compared with baseline in the SOD of all measurable enhancing lesions sustained.

Outcome measures

Outcome measures
Measure	Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg n=3 Participants Participants received epacadostat 25 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg n=6 Participants Participants received epacadostat 50 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg n=14 Participants Participants received epacadostat 100 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 300 mg + Nivolumab 3 mg n=13 Participants Participants received epacadostat 300 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + 5-FU/Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with 5-FU/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Pemetrexed/ Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Pemetrexed /Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Paclitaxel/ Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Paclitaxel/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in SCCHN Participants with SCCHN received epacadostat 100/300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in Glioblastoma Participants with Glioblastoma received epacadostat 100/300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle.
Phase 1, Part 1: ORR Per RECIST v1.1 for Participants With Solid Tumors; Per Cheson Criteria for Participants With B-cell NHL; and Per RANO and mRANO Criteria for Participants With GBM	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	23.1 percentage of participants	—	—	—	—	—

SECONDARY outcome

Timeframe: From first dose up end of the study (up to approximately 6 years)

Population: The Phase 1, Part 2 Full Analysis Population includes all participants enrolled in the study who received at least 1 dose of study drug. The data is reported only for responders for this outcome measure.

DOR is defined as the time from the first overall response contributing to an objective response (CR or PR) to the earlier of the participant's death and first overall response of PD. CR was defined as disappearance of all target lesions. PR was defined as At least a 30% decrease in the SOD of target lesions, taking as reference the Baseline sum diameters. PD was defined as at least a 20% increase in the SOD of target lesions.

Outcome measures

Outcome measures
Measure	Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg n=3 Participants Participants received epacadostat 25 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg n=1 Participants Participants received epacadostat 50 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg n=3 Participants Participants received epacadostat 100 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 300 mg + Nivolumab 3 mg Participants received epacadostat 300 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + 5-FU/Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with 5-FU/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Pemetrexed/ Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Pemetrexed /Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Paclitaxel/ Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Paclitaxel/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in SCCHN Participants with SCCHN received epacadostat 100/300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in Glioblastoma Participants with Glioblastoma received epacadostat 100/300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle.
Phase 1, Part 2: Duration of Response (DOR) for Participants With Advanced or Metastatic SCCHN and Advanced or Metastatic NSCLC	3.82 months Interval 3.75 to The upper limit of the confidence interval was not estimable because too few participants had disease progression or died.	NA months The median value can't be reported for a single participant due to the risk of patient re-identification.	3.93 months Interval 2.76 to The upper limit of the confidence interval was not estimable because too few participants had disease progression or died.	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From first dose up end of the study (up to approximately 6 years)

Population: The Phase 1, Part 2 Full Analysis Population includes all participants enrolled in the study who received at least 1 dose of study drug.

PFS is defined as the time from randomization to the first documented progressive disease or death due to any cause, whichever occurs first.

Outcome measures

Outcome measures
Measure	Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg n=6 Participants Participants received epacadostat 25 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg n=3 Participants Participants received epacadostat 50 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg n=3 Participants Participants received epacadostat 100 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 300 mg + Nivolumab 3 mg Participants received epacadostat 300 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + 5-FU/Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with 5-FU/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Pemetrexed/ Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Pemetrexed /Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Paclitaxel/ Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Paclitaxel/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in SCCHN Participants with SCCHN received epacadostat 100/300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in Glioblastoma Participants with Glioblastoma received epacadostat 100/300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle.
Phase 1, Part 2: PFS for Participants With Advanced or Metastatic SCCHN and Advanced or Metastatic NSCLC	5.72 months Interval 2.07 to The upper limit of the confidence interval was not estimable because too few participants had disease progression or died.	2.83 months Interval 1.35 to The upper limit of the confidence interval was not estimable because too few participants had disease progression or died.	6.10 months Interval 4.84 to The upper limit of the confidence interval was not estimable because too few participants had disease progression or died.	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From first dose up end of the study (up to approximately 6 years)

Population: The Phase 2 Full Analysis Population includes all participants enrolled in the study who received at least 1 dose of study drug. The data is reported only for responders and per cancer type for this outcome measure.

DOR is defined as the time from the first overall response contributing to an objective response (CR or PR) to the earlier of the participant's death and first overall response of PD. CR was defined as disappearance of all target lesions. PR was defined as At least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the Baseline sum diameters. PD was defined as at least a 20% increase in the SOD of target lesions.

Outcome measures

Outcome measures
Measure	Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg n=1 Participants Participants received epacadostat 25 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg Participants received epacadostat 50 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg n=31 Participants Participants received epacadostat 100 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 300 mg + Nivolumab 3 mg n=1 Participants Participants received epacadostat 300 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + 5-FU/Platinum n=2 Participants Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with 5-FU/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Pemetrexed/ Platinum n=12 Participants Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Pemetrexed /Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Paclitaxel/ Platinum n=4 Participants Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Paclitaxel/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in SCCHN n=8 Participants Participants with SCCHN received epacadostat 100/300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in Glioblastoma Participants with Glioblastoma received epacadostat 100/300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle.
Phase 2: Duration of Response	NA months Median, lower and upper limit of 95% CI was not estimable for 1 participant.	—	NA months Median, lower and upper limit of 95% CI was not estimable due to low number of participants with events.	NA months Median, lower and upper limit of 95% CI was not estimable for 1 participant.	NA months Median and 95% CI was not estimable due to low number of participants with events.	NA months Interval 1.94 to Median and upper limit of 95% CI was not estimable due to low number of participants with events.	3.93 months Interval 3.13 to 5.53	NA months Interval 7.37 to Median and upper limit of 95% CI was not estimable due to low number of participants with events.	—

SECONDARY outcome

Timeframe: From first dose up end of the study (up to approximately 6 years)

Population: The Phase 2 Full Analysis Population includes all participants enrolled in the study who received at least 1 dose of study drug. The data is reported per cancer type in this outcome measure. Overall number analyzed are the participants who had best overall response of stable disease or better.

Duration of disease control is the time from the first dose to the first objective response of PD, or death, whichever occurs first, for participants who reported a best overall response of SD or better. PD was defined as at least a 20% increase in the SOD of target lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the Baseline sum diameters.

Outcome measures

Outcome measures
Measure	Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg n=4 Participants Participants received epacadostat 25 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg n=4 Participants Participants received epacadostat 50 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg n=39 Participants Participants received epacadostat 100 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 300 mg + Nivolumab 3 mg n=2 Participants Participants received epacadostat 300 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + 5-FU/Platinum n=3 Participants Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with 5-FU/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Pemetrexed/ Platinum n=19 Participants Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Pemetrexed /Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Paclitaxel/ Platinum n=9 Participants Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Paclitaxel/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in SCCHN n=17 Participants Participants with SCCHN received epacadostat 100/300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in Glioblastoma n=8 Participants Participants with Glioblastoma received epacadostat 100/300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle.
Phase 2: Duration of Disease Control, Defined as CR, PR, and Stable Disease (SD)	3.72 months Interval 2.86 to Upper limit of 95% CI was not estimable due to low number of participants with events.	4.57 months Interval 3.52 to 10.26	NA months Median, lower and upper limit of 95% CI was not estimable due to low number of participants with events.	NA months Median, lower and upper limit of 95% CI was not estimable due to low number of participants with events.	NA months Interval 3.19 to Median, and upper limit of 95% CI was not estimable due to low number of participants with events.	NA months Interval 9.11 to Median, and upper limit of 95% CI was not estimable due to low number of participants with events.	5.86 months Interval 3.52 to 7.47	10.89 months Interval 4.84 to Upper limit of 95% CI was not estimable due to low number of participants with events.	3.72 months Interval 3.49 to 5.59

SECONDARY outcome

Timeframe: up to approximately 35 months

Population: The Phase 2 Safety population includes all participants enrolled in the study who received at least 1 dose of study drug.

An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and up to 100 days after last dose of study drug. Adverse events of grade 5 which result in death are called as fatal AEs.

Outcome measures

Outcome measures
Measure	Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg n=83 Participants Participants received epacadostat 25 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg n=176 Participants Participants received epacadostat 50 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg Participants received epacadostat 100 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 300 mg + Nivolumab 3 mg Participants received epacadostat 300 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + 5-FU/Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with 5-FU/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Pemetrexed/ Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Pemetrexed /Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Paclitaxel/ Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Paclitaxel/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in SCCHN Participants with SCCHN received epacadostat 100/300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in Glioblastoma Participants with Glioblastoma received epacadostat 100/300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle.
Phase 2: Safety and Tolerability Measured by the Number of Adverse Events (AEs), Serious Adverse Events (SAEs), and Fatal Treatment Emergent AEs Participants with Treatment Emergent Adverse Events	82 Participants	176 Participants	—	—	—	—	—	—	—
Phase 2: Safety and Tolerability Measured by the Number of Adverse Events (AEs), Serious Adverse Events (SAEs), and Fatal Treatment Emergent AEs Participants with Serious Treatment Emergent AEs	40 Participants	89 Participants	—	—	—	—	—	—	—
Phase 2: Safety and Tolerability Measured by the Number of Adverse Events (AEs), Serious Adverse Events (SAEs), and Fatal Treatment Emergent AEs Participants with Fatal Treatment Emergent AEs	4 Participants	5 Participants	—	—	—	—	—	—	—

Adverse Events

Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 2 deaths

Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg

Serious events: 3 serious events

Other events: 6 other events

Deaths: 4 deaths

Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg

Serious events: 4 serious events

Other events: 14 other events

Deaths: 11 deaths

Phase 1, Part 1: Epacadostat 300 mg + Nivolumab 3 mg

Serious events: 4 serious events

Other events: 13 other events

Deaths: 7 deaths

Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + 5-FU/Platinum

Serious events: 4 serious events

Other events: 6 other events

Deaths: 4 deaths

Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Pemetrexed/ Platinum

Serious events: 2 serious events

Other events: 3 other events

Deaths: 3 deaths

Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Paclitaxel/ Platinum

Serious events: 2 serious events

Other events: 3 other events

Deaths: 2 deaths

Phase 2: Epacadostat 100 mg + Nivolumab 240/480 mg

Serious events: 40 serious events

Other events: 81 other events

Deaths: 52 deaths

Phase 2: Epacadostat 300 mg + Nivolumab 240 mg

Serious events: 89 serious events

Other events: 173 other events

Deaths: 97 deaths

Total

Serious events: 148 serious events

Other events: 302 other events

Deaths: 182 deaths

Serious adverse events

Serious adverse events
Measure	Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg n=3 participants at risk Participants received epacadostat 25 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg n=6 participants at risk Participants received epacadostat 50 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg n=14 participants at risk Participants received epacadostat 100 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 300 mg + Nivolumab 3 mg n=13 participants at risk Participants received epacadostat 300 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + 5-FU/Platinum n=6 participants at risk Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with 5-FU/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Pemetrexed/ Platinum n=3 participants at risk Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Pemetrexed /Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Paclitaxel/ Platinum n=3 participants at risk Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Paclitaxel/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated	Phase 2: Epacadostat 100 mg + Nivolumab 240/480 mg n=83 participants at risk Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 and participants with melanoma I/O-relapsed and melanoma I/O-refractory enrolled in this arm received epacadostat 100 mg BID in combination with nivolumab 480 mg IV infusion Q4W on Days 1 and Day 29 of each 8-week cycle.	Phase 2: Epacadostat 300 mg + Nivolumab 240 mg n=176 participants at risk Participants with select solid tumor types received epacadostat 300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle.	Total n=307 participants at risk Total
Gastrointestinal disorders Large intestine perforation	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Skin and subcutaneous tissue disorders Drug reaction with eosinophilia and systemic symptoms	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Duodenal perforation	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Dysphagia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.4% 2/83 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.4% 6/176 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.6% 11/307 • Number of events 12 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Vascular disorders Embolism	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Abdominal infection	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.3% 4/176 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.3% 4/307 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Cardiac disorders Acute myocardial infarction	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Endocrine disorders Adrenal insufficiency	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Endocrine disorders Adrenocortical insufficiency acute	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Blood and lymphatic system disorders Anaemia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.4% 2/83 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Aphasia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Vascular disorders Arterial haemorrhage	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Ascites	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.6% 3/83 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.3% 4/307 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
General disorders Asthenia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.4% 2/83 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.6% 5/307 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Cardiac disorders Atrial fibrillation	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Cardiac disorders Atrioventricular block complete	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Hepatobiliary disorders Autoimmune hepatitis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.7% 3/176 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Investigations Blood alkaline phosphatase increased	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Investigations Blood bilirubin increased	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Investigations Blood creatinine increased	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Cardiac disorders Bradycardia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Brain compression	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain neoplasm malignant	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Brain oedema	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Bronchitis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Cardiac disorders Cardiac arrest	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Cauda equina syndrome	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Cellulitis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Central nervous system infection	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Cerebrovascular accident	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Hepatobiliary disorders Cholecystitis acute	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Hepatobiliary disorders Cholelithiasis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.7% 3/176 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Clostridium difficile colitis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Colitis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Psychiatric disorders Confusional state	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Convulsion	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.4% 6/176 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.3% 7/307 • Number of events 7 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.7% 3/176 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Vascular disorders Deep vein thrombosis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.6% 5/307 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Psychiatric disorders Delirium	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Depressed level of consciousness	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Diarrhoea	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.7% 3/176 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.3% 4/307 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Dizziness	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Immune system disorders Drug hypersensitivity	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Encephalopathy	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.6% 3/83 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.7% 3/176 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.3% 7/307 • Number of events 8 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Enterocolitis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Enterovesical fistula	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Skin and subcutaneous tissue disorders Erythema multiforme	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Vascular disorders Exsanguination	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Facial paresis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Injury, poisoning and procedural complications Fall	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
General disorders Fatigue	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.6% 5/307 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Injury, poisoning and procedural complications Femur fracture	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Vascular disorders Flushing	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
General disorders Gait disturbance	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Gastric ulcer perforation	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Gastroenteritis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Gastroenteritis viral	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Renal and urinary disorders Haematuria	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Blood and lymphatic system disorders Haemolytic anaemia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Haemorrhage intracranial	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Injury, poisoning and procedural complications Head injury	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Headache	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.3% 4/176 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.6% 5/307 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Hemianopia homonymous	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Hemiparesis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.4% 2/83 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Herpes zoster	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Injury, poisoning and procedural complications Hip fracture	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.7% 3/176 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Hydrocephalus	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Immune system disorders Hypersensitivity	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.6% 3/83 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.3% 4/176 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.9% 9/307 • Number of events 10 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Vascular disorders Hypotension	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.8% 5/176 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.0% 6/307 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Ileus	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.4% 2/83 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Blood and lymphatic system disorders Immune thrombocytopenic purpura	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Influenza	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Metabolism and nutrition disorders Lactic acidosis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Large intestinal obstruction	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Investigations Lipase increased	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Lumbar radiculopathy	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Lung infection	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.7% 3/176 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.3% 4/307 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant ascites	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Psychiatric disorders Mental status changes	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.8% 4/83 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.6% 5/307 • Number of events 7 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Metabolism and nutrition disorders Metabolic acidosis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Metabolic encephalopathy	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to peritoneum	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Injury, poisoning and procedural complications Muscle rupture	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.4% 2/83 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Cardiac disorders Myocardial infarction	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Myoclonus	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Nausea	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.4% 2/83 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.8% 5/176 • Number of events 7 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.3% 7/307 • Number of events 9 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Blood and lymphatic system disorders Neutropenia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
General disorders Non-cardiac chest pain	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Obstruction gastric	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Obstructive airways disorder	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
General disorders Oedema	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Ophthalmic herpes zoster	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Vascular disorders Orthostatic hypotension	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
General disorders Pain	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Pelvic abscess	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Pelvic infection	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Peripheral motor neuropathy	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Investigations Platelet count decreased	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.8% 5/176 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.3% 7/307 • Number of events 8 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Pneumonia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	66.7% 2/3 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.6% 3/83 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.5% 8/176 • Number of events 9 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.9% 15/307 • Number of events 17 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.3% 4/176 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.0% 6/307 • Number of events 7 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Pneumonia klebsiella	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Injury, poisoning and procedural complications Post procedural haemorrhage	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.3% 4/176 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.6% 5/307 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
General disorders Pyrexia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.3% 4/176 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.6% 5/307 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Injury, poisoning and procedural complications Radiation necrosis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Skin and subcutaneous tissue disorders Rash	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.7% 3/176 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.6% 5/307 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Rectal perforation	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Renal and urinary disorders Renal failure acute	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.4% 2/83 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.7% 3/176 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.0% 6/307 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Sepsis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	15.4% 2/13 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.6% 5/307 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Septic shock	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Cardiac disorders Sinus tachycardia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Sinusitis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	14.3% 2/14 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.8% 4/83 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.3% 7/307 • Number of events 9 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Spinal cord compression	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.4% 2/83 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Staphylococcal bacteraemia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Status epilepticus	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Stomatitis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Psychiatric disorders Suicide attempt	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Vascular disorders Superior vena cava syndrome	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Skin and subcutaneous tissue disorders Swelling face	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Syncope	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
General disorders Systemic inflammatory response syndrome	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Vascular disorders Thrombosis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Tremor	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Upper respiratory tract infection	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Urinary tract infection	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Urosepsis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders VIIth nerve paralysis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Vasogenic cerebral oedema	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Viral infection	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Vomiting	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.4% 2/83 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.4% 6/176 • Number of events 8 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.6% 8/307 • Number of events 10 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Investigations White blood cell count decreased	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Injury, poisoning and procedural complications Wound dehiscence	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Wound infection	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .

Other adverse events

Other adverse events
Measure	Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg n=3 participants at risk Participants received epacadostat 25 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg n=6 participants at risk Participants received epacadostat 50 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg n=14 participants at risk Participants received epacadostat 100 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 1: Epacadostat 300 mg + Nivolumab 3 mg n=13 participants at risk Participants received epacadostat 300 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + 5-FU/Platinum n=6 participants at risk Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with 5-FU/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Pemetrexed/ Platinum n=3 participants at risk Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Pemetrexed /Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated.	Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Paclitaxel/ Platinum n=3 participants at risk Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Paclitaxel/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated	Phase 2: Epacadostat 100 mg + Nivolumab 240/480 mg n=83 participants at risk Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 and participants with melanoma I/O-relapsed and melanoma I/O-refractory enrolled in this arm received epacadostat 100 mg BID in combination with nivolumab 480 mg IV infusion Q4W on Days 1 and Day 29 of each 8-week cycle.	Phase 2: Epacadostat 300 mg + Nivolumab 240 mg n=176 participants at risk Participants with select solid tumor types received epacadostat 300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle.	Total n=307 participants at risk Total
Investigations White blood cell count decreased	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.8% 4/83 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	5.1% 9/176 • Number of events 12 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.2% 13/307 • Number of events 16 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Eye disorders Vision blurred	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 2/6 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.8% 4/83 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	5.1% 9/176 • Number of events 10 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	5.9% 18/307 • Number of events 20 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Eye disorders Visual impairment	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.4% 2/83 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.7% 3/176 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.0% 6/307 • Number of events 9 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Investigations Vitamin B1 decreased	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Metabolism and nutrition disorders Vitamin B12 deficiency	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Metabolism and nutrition disorders Vitamin D deficiency	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Vomiting	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	28.6% 4/14 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	30.8% 4/13 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 2/6 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	20.5% 17/83 • Number of events 21 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	24.4% 43/176 • Number of events 64 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	23.1% 71/307 • Number of events 101 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Reproductive system and breast disorders Vulvovaginal pain	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Investigations Weight decreased	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 2/6 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	14.3% 2/14 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 2/6 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	66.7% 2/3 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	10.8% 9/83 • Number of events 9 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	14.8% 26/176 • Number of events 29 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	14.3% 44/307 • Number of events 47 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Investigations Weight increased	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.2% 6/83 • Number of events 8 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.8% 5/176 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.9% 12/307 • Number of events 14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.6% 3/83 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.0% 7/176 • Number of events 9 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.6% 11/307 • Number of events 13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Injury, poisoning and procedural complications Wound	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Abdominal pain upper	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	14.3% 2/14 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.6% 3/83 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.0% 7/176 • Number of events 7 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.9% 12/307 • Number of events 12 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Psychiatric disorders Agitation	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.3% 4/307 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Investigations Alanine aminotransferase increased	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	15.4% 2/13 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	14.5% 12/83 • Number of events 17 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	21.0% 37/176 • Number of events 51 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	17.3% 53/307 • Number of events 73 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Skin and subcutaneous tissue disorders Alopecia	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	66.7% 2/3 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.6% 3/83 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.6% 8/307 • Number of events 9 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Investigations Amylase increased	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	15.4% 2/13 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	10.8% 9/83 • Number of events 15 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	9.1% 16/176 • Number of events 21 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	9.4% 29/307 • Number of events 43 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	14.3% 2/14 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	15.4% 2/13 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	14.5% 12/83 • Number of events 20 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	8.0% 14/176 • Number of events 18 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	10.7% 33/307 • Number of events 46 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	6.0% 5/83 • Number of events 9 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.0% 7/176 • Number of events 12 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.6% 14/307 • Number of events 23 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 2/6 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	15.7% 13/83 • Number of events 23 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	15.9% 28/176 • Number of events 35 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	14.7% 45/307 • Number of events 62 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.8% 4/83 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	5.7% 10/176 • Number of events 16 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.6% 14/307 • Number of events 21 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Abdominal distension	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	28.6% 4/14 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.2% 6/83 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.2% 13/307 • Number of events 13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Abdominal pain	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	35.7% 5/14 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	23.1% 3/13 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.9% 14/83 • Number of events 19 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	10.2% 18/176 • Number of events 20 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	14.0% 43/307 • Number of events 50 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Abdominal pain lower	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Blood and lymphatic system disorders Anaemia	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 2/6 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	21.4% 3/14 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	15.4% 2/13 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	66.7% 4/6 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	66.7% 2/3 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	20.5% 17/83 • Number of events 22 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	17.0% 30/176 • Number of events 42 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	20.2% 62/307 • Number of events 80 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Injury, poisoning and procedural complications Animal bite	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Anorectal discomfort	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Psychiatric disorders Anxiety	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	6.0% 5/83 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	6.8% 12/176 • Number of events 12 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	6.2% 19/307 • Number of events 20 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Aphasia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.3% 4/176 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.6% 5/307 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Musculoskeletal and connective tissue disorders Arthralgia	66.7% 2/3 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	14.3% 2/14 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	14.5% 12/83 • Number of events 13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	14.2% 25/176 • Number of events 33 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	13.7% 42/307 • Number of events 54 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Ascites	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	14.3% 2/14 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.4% 2/83 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.6% 5/307 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Investigations Aspartate aminotransferase increased	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	23.1% 3/13 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	20.5% 17/83 • Number of events 27 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	22.2% 39/176 • Number of events 58 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	19.9% 61/307 • Number of events 93 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	21.4% 3/14 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	13.3% 11/83 • Number of events 12 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	17.0% 30/176 • Number of events 35 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	14.7% 45/307 • Number of events 51 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Investigations Blood albumin decreased	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.2% 6/83 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.3% 7/307 • Number of events 7 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Investigations Blood alkaline phosphatase increased	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	18.1% 15/83 • Number of events 25 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	13.1% 23/176 • Number of events 27 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	13.0% 40/307 • Number of events 54 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Investigations Blood bilirubin increased	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.8% 4/83 • Number of events 7 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.3% 4/176 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.9% 9/307 • Number of events 12 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Investigations Blood creatine phosphokinase increased	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Investigations Blood creatinine increased	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	14.3% 2/14 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	15.4% 2/13 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	19.3% 16/83 • Number of events 26 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.4% 13/176 • Number of events 21 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	11.4% 35/307 • Number of events 53 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Investigations Blood uric acid increased	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.3% 4/307 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Bronchitis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	15.4% 2/13 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.4% 2/83 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.6% 5/307 • Number of events 7 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Candida infection	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.6% 5/307 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Investigations Carcinoembryonic antigen increased	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
General disorders Chest pain	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
General disorders Chills	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	12.0% 10/83 • Number of events 11 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.5% 8/176 • Number of events 10 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.2% 22/307 • Number of events 25 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Renal and urinary disorders Chromaturia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Colitis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Psychiatric disorders Confusional state	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.4% 2/83 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.0% 7/176 • Number of events 10 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.6% 11/307 • Number of events 14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Constipation	66.7% 2/3 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 2/6 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	14.3% 2/14 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	23.1% 3/13 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 2/6 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	66.7% 2/3 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	30.1% 25/83 • Number of events 26 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	29.0% 51/176 • Number of events 57 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	29.3% 90/307 • Number of events 99 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Immune system disorders Contrast media allergy	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Injury, poisoning and procedural complications Contusion	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.6% 3/83 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.7% 3/176 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.3% 7/307 • Number of events 7 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Convulsion	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Musculoskeletal and connective tissue disorders Costochondritis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Cough	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	14.3% 2/14 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	30.8% 4/13 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 2/6 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	66.7% 2/3 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	22.9% 19/83 • Number of events 23 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	23.3% 41/176 • Number of events 50 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	23.5% 72/307 • Number of events 86 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Metabolism and nutrition disorders Decreased appetite	33.3% 1/3 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 2/6 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	50.0% 7/14 • Number of events 7 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	66.7% 2/3 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	26.5% 22/83 • Number of events 24 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	35.2% 62/176 • Number of events 69 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	31.9% 98/307 • Number of events 109 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 2/6 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.6% 3/83 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	10.8% 19/176 • Number of events 28 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	8.1% 25/307 • Number of events 34 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Psychiatric disorders Depression	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	50.0% 3/6 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.8% 4/83 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	6.2% 11/176 • Number of events 11 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	5.9% 18/307 • Number of events 18 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Skin and subcutaneous tissue disorders Dermatitis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.0% 7/176 • Number of events 9 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.9% 9/307 • Number of events 11 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Skin and subcutaneous tissue disorders Dermatitis acneiform	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.3% 4/307 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Diarrhoea	66.7% 2/3 • Number of events 7 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	21.4% 3/14 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	15.4% 2/13 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	66.7% 4/6 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	30.1% 25/83 • Number of events 32 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.0% 58/176 • Number of events 91 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	31.3% 96/307 • Number of events 149 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Eye disorders Diplopia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Dizziness	33.3% 1/3 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	14.5% 12/83 • Number of events 13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	15.9% 28/176 • Number of events 32 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	13.7% 42/307 • Number of events 49 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Eye disorders Dry eye	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	15.4% 2/13 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.0% 7/176 • Number of events 7 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.9% 9/307 • Number of events 9 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Dry mouth	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	8.4% 7/83 • Number of events 7 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	5.7% 10/176 • Number of events 11 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	6.2% 19/307 • Number of events 20 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.5% 8/176 • Number of events 8 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.3% 10/307 • Number of events 10 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Dysgeusia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	50.0% 3/6 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	66.7% 2/3 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.6% 3/83 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	8.0% 14/176 • Number of events 14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.8% 24/307 • Number of events 25 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Dyspepsia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	14.3% 2/14 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	30.8% 4/13 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.8% 4/83 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.4% 13/176 • Number of events 13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.8% 24/307 • Number of events 24 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Dysphagia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.8% 4/83 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.5% 8/176 • Number of events 8 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.6% 14/307 • Number of events 15 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.8% 5/176 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.6% 8/307 • Number of events 8 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Dyspnoea	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	30.8% 4/13 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	25.3% 21/83 • Number of events 22 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	17.0% 30/176 • Number of events 34 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	19.2% 59/307 • Number of events 68 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.7% 3/176 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.3% 4/307 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Renal and urinary disorders Dysuria	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.3% 4/307 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Ear and labyrinth disorders Ear discomfort	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Ear infection	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Ear and labyrinth disorders Ear pain	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 2/6 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.8% 5/176 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.6% 8/307 • Number of events 9 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.8% 5/176 • Number of events 7 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.0% 6/307 • Number of events 8 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Skin and subcutaneous tissue disorders Erythema	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.6% 3/83 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.3% 4/176 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.6% 8/307 • Number of events 8 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Eye disorders Eye pruritus	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
General disorders Face oedema	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
General disorders Facial pain	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Faecal incontinence	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Injury, poisoning and procedural complications Fall	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.8% 4/83 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	11.9% 21/176 • Number of events 24 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	9.1% 28/307 • Number of events 31 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
General disorders Fatigue	100.0% 3/3 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	50.0% 3/6 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	28.6% 4/14 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	15.4% 2/13 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	66.7% 4/6 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	100.0% 3/3 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	66.7% 2/3 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	43.4% 36/83 • Number of events 38 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	69.9% 123/176 • Number of events 131 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	58.6% 180/307 • Number of events 194 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Flatulence	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.4% 2/83 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.3% 4/176 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.3% 7/307 • Number of events 7 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
General disorders Gait disturbance	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Investigations Gamma-glutamyltransferase increased	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	6.0% 5/83 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	5.1% 9/176 • Number of events 9 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	5.2% 16/307 • Number of events 16 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Gingival bleeding	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Glossodynia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Musculoskeletal and connective tissue disorders Groin pain	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.4% 2/83 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.0% 6/307 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Renal and urinary disorders Haematuria	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.8% 4/83 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.6% 8/307 • Number of events 10 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Haemoptysis	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.7% 3/176 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.6% 5/307 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Head discomfort	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Headache	66.7% 2/3 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 2/6 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	14.3% 2/14 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	15.4% 2/13 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	18.1% 15/83 • Number of events 17 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	22.7% 40/176 • Number of events 52 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	20.8% 64/307 • Number of events 80 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Hemiparesis	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	5.1% 9/176 • Number of events 12 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.6% 11/307 • Number of events 14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Investigations Hepatic enzyme increased	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Herpes zoster	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Vascular disorders Hot flush	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.6% 3/83 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.3% 4/176 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.6% 8/307 • Number of events 9 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.3% 4/176 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.0% 6/307 • Number of events 7 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	9.6% 8/83 • Number of events 10 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	6.8% 12/176 • Number of events 17 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	6.8% 21/307 • Number of events 28 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Vascular disorders Hypertension	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	15.7% 13/83 • Number of events 17 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	9.1% 16/176 • Number of events 32 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	10.1% 31/307 • Number of events 51 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Endocrine disorders Hyperthyroidism	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.4% 2/83 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.8% 5/176 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.6% 8/307 • Number of events 8 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Metabolism and nutrition disorders Hyperuricaemia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	8.4% 7/83 • Number of events 14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.7% 3/176 • Number of events 8 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.9% 12/307 • Number of events 24 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Hypoaesthesia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 2/6 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.8% 5/176 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.3% 7/307 • Number of events 7 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	6.0% 5/83 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	8.0% 14/176 • Number of events 16 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	6.8% 21/307 • Number of events 24 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.6% 3/83 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	5.1% 9/176 • Number of events 13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.6% 14/307 • Number of events 18 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Endocrine disorders Hypogonadism	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Vascular disorders Hypotension	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.2% 6/83 • Number of events 7 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	9.1% 16/176 • Number of events 18 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.5% 23/307 • Number of events 26 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Endocrine disorders Hypothyroidism	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 2/6 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	14.5% 12/83 • Number of events 13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	11.4% 20/176 • Number of events 21 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	12.1% 37/307 • Number of events 39 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	15.4% 2/13 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.4% 2/83 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	5.1% 9/176 • Number of events 10 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.9% 15/307 • Number of events 17 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Blood and lymphatic system disorders Increased tendency to bruise	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Increased upper airway secretion	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
General disorders Influenza like illness	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.8% 4/83 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.3% 7/307 • Number of events 9 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	15.4% 2/13 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.8% 4/83 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.5% 8/176 • Number of events 10 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.9% 15/307 • Number of events 19 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Inguinal hernia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Psychiatric disorders Insomnia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	21.4% 3/14 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	23.1% 3/13 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	50.0% 3/6 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	10.8% 9/83 • Number of events 9 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	14.2% 25/176 • Number of events 25 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	14.0% 43/307 • Number of events 43 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Hepatobiliary disorders Jaundice	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Musculoskeletal and connective tissue disorders Joint swelling	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Blood and lymphatic system disorders Leukocytosis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Blood and lymphatic system disorders Leukopenia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Investigations Lipase increased	33.3% 1/3 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	30.8% 4/13 • Number of events 12 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	9.6% 8/83 • Number of events 11 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	11.4% 20/176 • Number of events 28 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	11.4% 35/307 • Number of events 55 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
General disorders Localised oedema	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Investigations Lymphocyte count decreased	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.2% 6/83 • Number of events 12 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	8.0% 14/176 • Number of events 18 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	6.5% 20/307 • Number of events 30 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Vascular disorders Lymphoedema	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.4% 2/83 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.6% 5/307 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Melaena	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Psychiatric disorders Mental status changes	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Mouth ulceration	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Mucosal infection	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.4% 2/83 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.4% 6/176 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.3% 10/307 • Number of events 11 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.4% 2/83 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.4% 6/176 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.3% 10/307 • Number of events 10 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.8% 4/83 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.4% 6/176 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.9% 12/307 • Number of events 12 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.6% 3/83 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.4% 13/176 • Number of events 13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	5.9% 18/307 • Number of events 18 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Musculoskeletal and connective tissue disorders Myalgia	66.7% 2/3 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	66.7% 2/3 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	14.5% 12/83 • Number of events 12 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	5.7% 10/176 • Number of events 13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	9.4% 29/307 • Number of events 34 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Myasthenia gravis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Musculoskeletal and connective tissue disorders Myositis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	6.0% 5/83 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	11.4% 20/176 • Number of events 24 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	8.5% 26/307 • Number of events 30 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Nasopharyngitis	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.4% 2/83 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.7% 3/176 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.3% 7/307 • Number of events 9 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Nausea	66.7% 2/3 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	42.9% 6/14 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	23.1% 3/13 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	50.0% 3/6 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	66.7% 2/3 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	36.1% 30/83 • Number of events 35 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	42.6% 75/176 • Number of events 99 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	39.7% 122/307 • Number of events 155 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.2% 6/83 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.5% 8/176 • Number of events 8 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	5.9% 18/307 • Number of events 18 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Neuralgia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.7% 3/176 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.3% 4/307 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Neuropathy peripheral	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.0% 7/176 • Number of events 7 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.3% 10/307 • Number of events 10 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Blood and lymphatic system disorders Neutropenia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.4% 2/83 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.7% 3/176 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.0% 6/307 • Number of events 7 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Skin and subcutaneous tissue disorders Night sweats	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.4% 2/83 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	5.1% 9/176 • Number of events 9 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.6% 11/307 • Number of events 11 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
General disorders Oedema	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
General disorders Oedema peripheral	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 2/6 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	18.1% 15/83 • Number of events 18 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	9.7% 17/176 • Number of events 18 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	12.1% 37/307 • Number of events 41 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Oral candidiasis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Oral herpes	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.7% 3/176 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.6% 5/307 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Oral mucosal eruption	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Oral pain	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 2/6 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	66.7% 2/3 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.0% 6/307 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.6% 3/83 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.4% 13/176 • Number of events 16 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	6.2% 19/307 • Number of events 25 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Oropharyngeal swelling	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.8% 4/83 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	6.2% 11/176 • Number of events 13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	5.5% 17/307 • Number of events 19 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Musculoskeletal and connective tissue disorders Pain in jaw	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.7% 3/176 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.6% 5/307 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Pancreatic insufficiency	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Pancreatitis acute	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Psychiatric disorders Panic attack	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Paraesthesia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.6% 3/83 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	6.2% 11/176 • Number of events 13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.9% 15/307 • Number of events 17 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Paranasal sinus hypersecretion	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Paronychia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Eye disorders Periorbital oedema	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	15.4% 2/13 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	66.7% 2/3 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.6% 3/83 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.8% 5/176 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.9% 12/307 • Number of events 12 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
General disorders Peripheral swelling	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.7% 3/176 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.3% 4/307 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Pharyngitis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Pharyngitis streptococcal	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Eye disorders Photophobia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Skin and subcutaneous tissue disorders Photosensitivity reaction	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Investigations Platelet count decreased	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 2/6 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	6.0% 5/83 • Number of events 14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.8% 5/176 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.2% 13/307 • Number of events 22 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	6.0% 5/83 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.7% 3/176 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.6% 8/307 • Number of events 8 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Pneumonia	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	6.2% 11/176 • Number of events 11 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.9% 12/307 • Number of events 12 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.7% 3/176 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.3% 4/307 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.7% 3/176 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.0% 6/307 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Renal and urinary disorders Pollakiuria	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.7% 3/176 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.3% 7/307 • Number of events 7 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Post herpetic neuralgia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Proctalgia	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.4% 2/83 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.4% 2/83 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	5.7% 10/176 • Number of events 11 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.9% 12/307 • Number of events 13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Skin and subcutaneous tissue disorders Pruritus	66.7% 2/3 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	30.8% 4/13 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	66.7% 4/6 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	19.3% 16/83 • Number of events 27 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	19.3% 34/176 • Number of events 44 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	20.2% 62/307 • Number of events 86 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Skin and subcutaneous tissue disorders Pruritus generalised	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.3% 4/176 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.3% 7/307 • Number of events 8 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Skin and subcutaneous tissue disorders Purpura	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
General disorders Pyrexia	66.7% 2/3 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	21.4% 3/14 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	15.4% 2/13 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	14.5% 12/83 • Number of events 16 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.5% 29/176 • Number of events 41 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	15.6% 48/307 • Number of events 66 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Skin and subcutaneous tissue disorders Rash	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	35.7% 5/14 • Number of events 7 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	30.8% 4/13 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	22.9% 19/83 • Number of events 25 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	22.2% 39/176 • Number of events 50 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	22.5% 69/307 • Number of events 89 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Skin and subcutaneous tissue disorders Rash generalised	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.4% 2/83 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.6% 5/307 • Number of events 7 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Skin and subcutaneous tissue disorders Rash macular	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	23.1% 3/13 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	13.3% 11/83 • Number of events 14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.5% 29/176 • Number of events 32 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	14.0% 43/307 • Number of events 49 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Skin and subcutaneous tissue disorders Rash papular	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.8% 4/83 • Number of events 7 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.7% 3/176 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.6% 8/307 • Number of events 11 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Rectal discharge	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Respiration abnormal	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Rhinitis	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.8% 4/83 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.0% 6/307 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.8% 4/83 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.3% 4/176 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.9% 9/307 • Number of events 10 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.3% 4/176 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.6% 5/307 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Salivary duct inflammation	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Salivary hypersecretion	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Reproductive system and breast disorders Scrotal oedema	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Sinus headache	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.4% 2/83 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.7% 3/176 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.0% 6/307 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Cardiac disorders Sinus tachycardia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	6.0% 5/83 • Number of events 7 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	5.7% 10/176 • Number of events 10 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.9% 15/307 • Number of events 17 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Sinusitis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	14.3% 2/14 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.8% 4/83 • Number of events 7 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.4% 6/176 • Number of events 7 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	4.2% 13/307 • Number of events 17 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Skin and subcutaneous tissue disorders Skin hypopigmentation	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.1% 2/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.98% 3/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Injury, poisoning and procedural complications Stoma site haemorrhage	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Injury, poisoning and procedural complications Stoma site pain	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Gastrointestinal disorders Stomatitis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	83.3% 5/6 • Number of events 9 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	6.0% 5/83 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	8.0% 14/176 • Number of events 15 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	8.1% 25/307 • Number of events 30 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Subcutaneous abscess	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Injury, poisoning and procedural complications Sunburn	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
General disorders Suprapubic pain	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Cardiac disorders Tachycardia	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.2% 6/83 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.4% 6/176 • Number of events 8 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	5.2% 16/307 • Number of events 18 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Musculoskeletal and connective tissue disorders Tendonitis	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Throat tightness	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Tooth infection	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Respiratory, thoracic and mediastinal disorders Tracheal pain	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Investigations Transaminases increased	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Nervous system disorders Tremor	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.4% 2/83 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.4% 6/176 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	3.6% 11/307 • Number of events 11 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Investigations Troponin I increased	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.7% 1/13 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Upper respiratory tract infection	100.0% 3/3 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	8.4% 7/83 • Number of events 8 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.4% 13/176 • Number of events 20 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.8% 24/307 • Number of events 33 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Renal and urinary disorders Urinary incontinence	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	66.7% 2/3 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.4% 2/83 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.7% 3/176 • Number of events 3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.6% 8/307 • Number of events 8 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Renal and urinary disorders Urinary retention	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	2.4% 2/83 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.6% 5/307 • Number of events 5 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Urinary tract infection	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	15.4% 2/13 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 4 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.2% 6/83 • Number of events 14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.4% 13/176 • Number of events 20 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	8.1% 25/307 • Number of events 43 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Renal and urinary disorders Urinary tract obstruction	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Skin and subcutaneous tissue disorders Urticaria	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	7.1% 1/14 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.2% 1/83 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	1.6% 5/307 • Number of events 6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Reproductive system and breast disorders Vaginal odour	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Ear and labyrinth disorders Vestibular disorder	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	33.3% 1/3 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/176 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.33% 1/307 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .
Infections and infestations Viral infection	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/6 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/14 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/13 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	16.7% 1/6 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/3 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.00% 0/83 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.57% 1/176 • Number of events 1 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .	0.65% 2/307 • Number of events 2 • up to approximately 39 months for Phase 1 and up to approximately 35 months for Phase 2 The safety population includes all subjects enrolled in the study who received at least 1 dose of study drug .

Additional Information

Study Director

Incyte Corporation

Phone: 1-855-463-3463

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Clinical Study Agreement
Publication restrictions are in place

Restriction type: OTHER