Trial Outcomes & Findings for Multiple Ascending Dose of BMS-911543 (NCT NCT01236352)

NCT ID: NCT01236352

Last Updated: 2019-07-31

Results Overview

Safety assessments were based on a medical review of adverse event reports and the results of vital sign measurements, ECGs, physical examinations, and clinical laboratory tests and were evaluated for all treated participants using National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 (NCI CTCAE v.4.0).

• Recruitment status: TERMINATED
• Study phase: PHASE1/PHASE2
• Target enrollment: 98 participants
• Primary outcome timeframe: From the date of participant's written consent until 30 days post discontinuation of dosing or participation in the study if the last scheduled visit occured at a later time, assessed up to 4.5 years
• Results posted on: 2019-07-31

Participant Flow

98 participants were enrolled and 84 participants were treated. 14 participants did not enter treatment period (13 no longer met study criteria and 1 due to other reasons). 42 entered Phase 1 and 42 entered Phase 2

Participant milestones

Measure	5 mg Phase I BMS-911543 5 mg capsule by mouth twice daily	10 mg Phase I BMS-911543 10 mg capsule by mouth twice daily	20 mg Phase I BMS-911543 20 mg capsule by mouth twice daily	40 mg Phase I BMS-911543 40 mg capsule by mouth twice daily	80 mg Phase I BMS-911543 80 mg capsule by mouth twice daily	120 mg Phase I BMS-911543 120 mg capsule by mouth twice daily	160 mg Phase I BMS-911543 160 mg capsule by mouth twice daily	200 mg Phase I BMS-911543 2000 mg capsule by mouth twice daily	240 mg Phase I BMS-911543 240 mg capsule by mouth twice daily	120 mg Phase II BMS-911543 120 mg capsule by mouth twice daily	200 mg Phase II BMS-911543 200 mg capsule by mouth twice daily
Overall Study STARTED	4	4	4	4	4	4	8	7	3	22	20
Overall Study COMPLETED	0	0	0	1	0	0	0	0	0	0	0
Overall Study NOT COMPLETED	4	4	4	3	4	4	8	7	3	22	20

Reasons for withdrawal

Measure	5 mg Phase I BMS-911543 5 mg capsule by mouth twice daily	10 mg Phase I BMS-911543 10 mg capsule by mouth twice daily	20 mg Phase I BMS-911543 20 mg capsule by mouth twice daily	40 mg Phase I BMS-911543 40 mg capsule by mouth twice daily	80 mg Phase I BMS-911543 80 mg capsule by mouth twice daily	120 mg Phase I BMS-911543 120 mg capsule by mouth twice daily	160 mg Phase I BMS-911543 160 mg capsule by mouth twice daily	200 mg Phase I BMS-911543 2000 mg capsule by mouth twice daily	240 mg Phase I BMS-911543 240 mg capsule by mouth twice daily	120 mg Phase II BMS-911543 120 mg capsule by mouth twice daily	200 mg Phase II BMS-911543 200 mg capsule by mouth twice daily
Overall Study Death	0	0	0	0	0	0	0	1	0	0	0
Overall Study Withdrawal by Subject	0	0	0	0	0	0	0	0	0	2	1
Overall Study Adverse Event	0	0	0	0	0	0	2	0	0	4	1
Overall Study Study drug toxicity	0	0	0	0	0	1	1	0	0	2	2
Overall Study Disease progression	1	2	1	2	2	2	1	3	2	2	2
Overall Study Poor/Non-compliance	1	0	0	0	0	0	0	0	0	0	0
Overall Study Maximum clinical benefit	1	1	1	0	2	0	3	1	1	4	2
Overall Study Subject request to discontinue treatment	0	0	1	1	0	1	0	0	0	1	4
Overall Study Subject to receive drug via EAP	1	1	1	0	0	0	0	2	0	4	0
Overall Study Patient moving to allogeneic transplant	0	0	0	0	0	0	1	0	0	0	0
Overall Study Relapse of Splenomegaly and symptoms	0	0	0	0	0	0	0	0	0	0	1
Overall Study Lack of response to drug	0	0	0	0	0	0	0	0	0	1	1
Overall Study Patient transferred to IST	0	0	0	0	0	0	0	0	0	2	6

Baseline Characteristics

Multiple Ascending Dose of BMS-911543

Baseline characteristics by cohort

Measure	5 mg Phase I n=4 Participants BMS-911543 5 mg capsule by mouth twice daily	10 mg Phase I n=4 Participants BMS-911543 10 mg capsule by mouth twice daily	20 mg Phase I n=4 Participants BMS-911543 20 mg capsule by mouth twice daily	40 mg Phase I n=4 Participants BMS-911543 40 mg capsule by mouth twice daily	80 mg Phase I n=4 Participants BMS-911543 80 mg capsule by mouth twice daily	120 mg Phase I n=4 Participants BMS-911543 120 mg capsule by mouth twice daily	160 mg Phase I n=8 Participants BMS-911543 160 mg capsule by mouth twice daily	200 mg Phase I n=7 Participants BMS-911543 2000 mg capsule by mouth twice daily	240 mg Phase I n=3 Participants BMS-911543 240 mg capsule by mouth twice daily	120 mg Phase II n=22 Participants BMS-911543 120 mg capsule by mouth twice daily	200 mg Phase II n=20 Participants BMS-911543 200 mg capsule by mouth twice daily	Total n=84 Participants Total of all reporting groups
Age, Continuous	76.8 Years STANDARD_DEVIATION 4.50 • n=5 Participants	56.5 Years STANDARD_DEVIATION 3.70 • n=7 Participants	70.5 Years STANDARD_DEVIATION 4.80 • n=5 Participants	64.0 Years STANDARD_DEVIATION 7.70 • n=4 Participants	69.8 Years STANDARD_DEVIATION 9.54 • n=21 Participants	63.3 Years STANDARD_DEVIATION 12.97 • n=8 Participants	70.1 Years STANDARD_DEVIATION 10.79 • n=8 Participants	62.3 Years STANDARD_DEVIATION 6.47 • n=24 Participants	63.0 Years STANDARD_DEVIATION 6.93 • n=42 Participants	61.0 Years STANDARD_DEVIATION 11.09 • n=42 Participants	62.5 Years STANDARD_DEVIATION 11.13 • n=42 Participants	64.0 Years STANDARD_DEVIATION 10.40 • n=42 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	2 Participants n=21 Participants	2 Participants n=8 Participants	4 Participants n=8 Participants	2 Participants n=24 Participants	1 Participants n=42 Participants	7 Participants n=42 Participants	12 Participants n=42 Participants	39 Participants n=42 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	2 Participants n=21 Participants	2 Participants n=8 Participants	4 Participants n=8 Participants	5 Participants n=24 Participants	2 Participants n=42 Participants	15 Participants n=42 Participants	8 Participants n=42 Participants	45 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=8 Participants	00 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	1 Participants n=42 Participants	0 Participants n=42 Participants	1 Participants n=42 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	3 Participants n=21 Participants	4 Participants n=8 Participants	7 Participants n=8 Participants	6 Participants n=24 Participants	3 Participants n=42 Participants	16 Participants n=42 Participants	19 Participants n=42 Participants	70 Participants n=42 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=8 Participants	1 Participants n=8 Participants	1 Participants n=24 Participants	0 Participants n=42 Participants	5 Participants n=42 Participants	1 Participants n=42 Participants	13 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=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
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=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
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=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
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	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants	4 Participants n=21 Participants	4 Participants n=8 Participants	8 Participants n=8 Participants	7 Participants n=24 Participants	3 Participants n=42 Participants	20 Participants n=42 Participants	20 Participants n=42 Participants	82 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=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	2 Participants n=42 Participants	0 Participants n=42 Participants	2 Participants n=42 Participants

PRIMARY outcome

Timeframe: From the date of participant's written consent until 30 days post discontinuation of dosing or participation in the study if the last scheduled visit occured at a later time, assessed up to 4.5 years

Population: All treated participants

Safety assessments were based on a medical review of adverse event reports and the results of vital sign measurements, ECGs, physical examinations, and clinical laboratory tests and were evaluated for all treated participants using National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 (NCI CTCAE v.4.0).

Outcome measures

Measure	5 mg Phase I n=4 Participants BMS-911543 5 mg capsule by mouth twice daily	10 mg Phase I n=4 Participants BMS-911543 10 mg capsule by mouth twice daily	20 mg Phase I n=4 Participants BMS-911543 20 mg capsule by mouth twice daily	40 mg Phase I n=4 Participants BMS-911543 40 mg capsule by mouth twice daily	80 mg Phase I n=4 Participants BMS-911543 80 mg capsule by mouth twice daily	120 mg Phase I n=4 Participants BMS-911543 120 mg capsule by mouth twice daily	160 mg Phase I n=8 Participants BMS-911543 160 mg capsule by mouth twice daily	200 mg Phase I n=7 Participants BMS-911543 2000 mg capsule by mouth twice daily	240 mg Phase I n=3 Participants BMS-911543 240 mg capsule by mouth twice daily	120 mg Phase II n=22 Participants BMS-911543 120 mg capsule by mouth twice daily	200 mg Phase II n=20 Participants BMS-911543 200 mg capsule by mouth twice daily
Number of Participants With Adverse Events No. of deaths	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	1 Participants	2 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Adverse Events No. of participants with Serious AEs	3 Participants	2 Participants	2 Participants	1 Participants	4 Participants	2 Participants	6 Participants	2 Participants	1 Participants	9 Participants	10 Participants
Number of Participants With Adverse Events No. of participants discontinued due to AEs	1 Participants	1 Participants	0 Participants	0 Participants	1 Participants	1 Participants	3 Participants	0 Participants	1 Participants	7 Participants	5 Participants
Number of Participants With Adverse Events Number of participants with AEs	4 Participants	4 Participants	4 Participants	4 Participants	4 Participants	4 Participants	8 Participants	7 Participants	3 Participants	22 Participants	20 Participants

PRIMARY outcome

Timeframe: Day 1, at each returning on-treatment visit and the first post-treatment visit

Population: All treated participants

Participants were clinically assessed for IWG-(International Working Group consensus criteria for treatment response in myelofibrosis with myeloid metaplasia) defined response at each returning on-treatment visit and the first post-treatment visit. IWG-MRT criteria for best overall response are ordered high to low: CR>PR>CI>SD>PD>R where CR = Complete Remission, PR= Partial Remission, CI = Clinical Improvement, SD = Stable Disease, PD = Progressive Disease and R = Relapse. Best overall response is the best response of the subject during the treatment period or at the first post-treatment visit.

Outcome measures

Measure	5 mg Phase I n=4 Participants BMS-911543 5 mg capsule by mouth twice daily	10 mg Phase I n=4 Participants BMS-911543 10 mg capsule by mouth twice daily	20 mg Phase I n=4 Participants BMS-911543 20 mg capsule by mouth twice daily	40 mg Phase I n=4 Participants BMS-911543 40 mg capsule by mouth twice daily	80 mg Phase I n=4 Participants BMS-911543 80 mg capsule by mouth twice daily	120 mg Phase I n=4 Participants BMS-911543 120 mg capsule by mouth twice daily	160 mg Phase I n=8 Participants BMS-911543 160 mg capsule by mouth twice daily	200 mg Phase I n=7 Participants BMS-911543 2000 mg capsule by mouth twice daily	240 mg Phase I n=3 Participants BMS-911543 240 mg capsule by mouth twice daily	120 mg Phase II n=22 Participants BMS-911543 120 mg capsule by mouth twice daily	200 mg Phase II n=20 Participants BMS-911543 200 mg capsule by mouth twice daily
Number of Participants With Best Overall Response Complete Remission	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Best Overall Response Partial Remission	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	2 Participants	1 Participants
Number of Participants With Best Overall Response Clinical Improvement	1 Participants	1 Participants	1 Participants	1 Participants	2 Participants	0 Participants	3 Participants	3 Participants	1 Participants	12 Participants	9 Participants
Number of Participants With Best Overall Response Stable Disease	3 Participants	2 Participants	3 Participants	3 Participants	1 Participants	4 Participants	4 Participants	3 Participants	2 Participants	6 Participants	10 Participants
Number of Participants With Best Overall Response Progressive Disease	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Best Overall Response Relapse	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 6 months

Population: Data for this outcome measure was not collected for any participants because the study was terminated

JAK/STAT pathway activity will be evaluated by: 1) pSTATs levels using immunoassay; 2) expression levels of several JAK/STATs pathway genes. Whole blood will be collected at specific time-points. Due to portfolio/business decisions by the sponsor, the compound is no longer being developed and the study was terminated. Analysis was not completed because the study was terminated. This decision was not based on any safety concerns associated with BMS-911543.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study

Population: Data for this outcome measure was not collected for any participants because the study was terminated

Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: Cmax Maximum observed plasma concentration

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study

Population: Data for this outcome measure was not collected for any participants because the study was terminated

Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: Cmin (Trough observed (pre-dose) plasma concentration)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study

Population: Data for this outcome measure was not collected for any participants because the study was terminated

Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: Tmax = Time of maximum observed plasma concentration (Tmax) of BMS-911543 and it's metabolite Met4

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study

Population: Data for this outcome measure was not collected for any participants because the study was terminated

Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: AUC(INF) = Area under the plasma concentration-time curve from time zero extrapolated to infinite time (for single dose period only) (AUC(INF)) of BMS-911543 and it's metabolite Met4

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study

Population: Data for this outcome measure was not collected for any participants because the study was terminated

Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: AUC (0-T) = Area under the plasma concentration-time curve from time zero to the time of last quantifiable plasma concentration (for single dose period only) of BMS-911543 and it's metabolite Met4

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study

Population: Data for this outcome measure was not collected for any participants because the study was terminated

Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: AUC (TAU) = Area under the concentration-time curve in one dosing interval of BMS-911543 and it's metabolite Met4

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study

Population: Data for this outcome measure was not collected for any participants because the study was terminated

Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: T-HALF = The terminal-phase elimination half-life in plasma of BMS-911543 and it's metabolite Met4

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study

Population: Data for this outcome measure was not collected for any participants because the study was terminated

Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: CLT/F = Apparent total clearance (for parent compound only) of BMS-911543 and it's metabolite Met4

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study

Population: Data for this outcome measure was not collected for any participants because the study was terminated

Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: Vz/F = Apparent volume of distribution after first dosing based on the terminal phase (for parent compound only) of BMS-911543 and it's metabolite Met4

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study

Population: Data for this outcome measure was not collected for any participants because the study was terminated

Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: Accumulation index (AI) = ratio of AUC(TAU) on Day 15 to AUC(TAU) after the first dose of BMS-911543 and it's metabolite Met4

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study

Population: Data for this outcome measure was not collected for any participants because the study was terminated

Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: AUC Ratio = Ratio of BMS-926796 AUC(INF) to BMS-911543 AUC(INF) after 1st dose and BMS-926796 AUC(TAU) to BMS-911543 AUC(TAU) on Day 15

Outcome measures

Outcome data not reported

Adverse Events

5 mg Phase I

Serious events: 3 serious events

Other events: 4 other events

Deaths: 1 deaths

10 mg Phase I

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

20 mg Phase I

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

40 mg Phase I

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

80 mg Phase I

Serious events: 4 serious events

Other events: 4 other events

Deaths: 1 deaths

120 mg Phase I

Serious events: 2 serious events

Other events: 4 other events

Deaths: 1 deaths

160 mg Phase I

Serious events: 6 serious events

Other events: 8 other events

Deaths: 1 deaths

200 mg Phase I

Serious events: 2 serious events

Other events: 7 other events

Deaths: 2 deaths

240 mg Phase I

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

120 mg Phase II

Serious events: 9 serious events

Other events: 22 other events

Deaths: 1 deaths

200 mg Phase II

Serious events: 10 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Measure	5 mg Phase I n=4 participants at risk BMS-911543 5 mg capsule by mouth twice daily	10 mg Phase I n=4 participants at risk BMS-911543 10 mg capsule by mouth twice daily	20 mg Phase I n=4 participants at risk BMS-911543 20 mg capsule by mouth twice daily	40 mg Phase I n=4 participants at risk BMS-911543 40 mg capsule by mouth twice daily	80 mg Phase I n=4 participants at risk BMS-911543 80 mg capsule by mouth twice daily	120 mg Phase I n=4 participants at risk BMS-911543 120 mg capsule by mouth twice daily	160 mg Phase I n=8 participants at risk BMS-911543 160 mg capsule by mouth twice daily	200 mg Phase I n=7 participants at risk BMS-911543 2000 mg capsule by mouth twice daily	240 mg Phase I n=3 participants at risk BMS-911543 240 mg capsule by mouth twice daily	120 mg Phase II n=22 participants at risk BMS-911543 120 mg capsule by mouth twice daily	200 mg Phase II n=20 participants at risk BMS-911543 200 mg capsule by mouth twice daily
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	14.3% 1/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Infections and infestations Cellulitis	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	5.0% 1/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Infections and infestations Lung infection	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Infections and infestations Pneumonia	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	9.1% 2/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Infections and infestations Abscess limb	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Infections and infestations Appendicitis	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Infections and infestations Atypical mycobacterial lymphadenitis	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	14.3% 1/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Infections and infestations Diverticulitis	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Infections and infestations Enterocolitis infectious	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Infections and infestations Gastroentiritis	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Infections and infestations Influenza	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	14.3% 1/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Infections and infestations Listeriosis	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Infections and infestations Postoperative wound infection	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Infections and infestations Sepsis	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Infections and infestations Sinusitis	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Infections and infestations Skin infection	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Infections and infestations Urinary tract infection	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Infections and infestations Viral infection	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Blood and lymphatic system disorders Spleen disorder	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	33.3% 1/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	9.1% 2/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Blood and lymphatic system disorders Anaemia	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	15.0% 3/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Injury, poisoning and procedural complications Facial bones fracture	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Blood and lymphatic system disorders Neutropenia	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	— 0/0 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Blood and lymphatic system disorders Pancytopenia	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Blood and lymphatic system disorders Splenic infarction	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	5.0% 1/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Gastrointestinal disorders Abdominal pain	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	33.3% 1/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Gastrointestinal disorders Colitis	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Gastrointestinal disorders Nausea	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Gastrointestinal disorders Pancreatitis	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	5.0% 1/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Gastrointestinal disorders Pancreatitis acute	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	5.0% 1/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
General disorders Disease progression	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
General disorders Multi-organ failure	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
General disorders Pyrexia	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	5.0% 1/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
General disorders Death	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	14.3% 1/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
General disorders Fatigue	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
General disorders Gait disturbance	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
General disorders Non-cardiac chest pain	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Cardiac disorders Atrial fibrillation	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	5.0% 1/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Cardiac disorders Cardiac failure	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	5.0% 1/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Cardiac disorders Cardiac failure congestive	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Cardiac disorders Sinus tachycardia	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Cardiac disorders Supraventricular Tachycardia	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	14.3% 1/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenoma benign	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	5.0% 1/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenosquamous cell carcinoma	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	14.3% 1/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Injury, poisoning and procedural complications Fall	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Injury, poisoning and procedural complications Hip fracture	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Injury, poisoning and procedural complications Subdural haematoma	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Respiratory, thoracic and mediastinal disorders Dyspnoea	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Vascular disorders Haematoma	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	10.0% 2/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Vascular disorders Blood pressure inadequately controlled	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Vascular disorders Capillary leak syndrome	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	5.0% 1/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	33.3% 1/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Musculoskeletal and connective tissue disorders Synovitis	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Renal and urinary disorders Acute kidney injury	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	5.0% 1/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Renal and urinary disorders Haematuria	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Renal and urinary disorders Nephrolithiasis	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Renal and urinary disorders Urinary tract obstruction	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Investigations Platelet count decreased	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	10.0% 2/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Nervous system disorders Syncope	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Nervous system disorders Tremor	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Endocrine disorders Inappropriate antidiuretic hormone secretion	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Hepatobiliary disorders Bile duct obstruction	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Hepatobiliary disorders Cholangitis	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Immune system disorders Cytokine release syndrome	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	5.0% 1/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Psychiatric disorders Confusional state	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)

Other adverse events

Measure	5 mg Phase I n=4 participants at risk BMS-911543 5 mg capsule by mouth twice daily	10 mg Phase I n=4 participants at risk BMS-911543 10 mg capsule by mouth twice daily	20 mg Phase I n=4 participants at risk BMS-911543 20 mg capsule by mouth twice daily	40 mg Phase I n=4 participants at risk BMS-911543 40 mg capsule by mouth twice daily	80 mg Phase I n=4 participants at risk BMS-911543 80 mg capsule by mouth twice daily	120 mg Phase I n=4 participants at risk BMS-911543 120 mg capsule by mouth twice daily	160 mg Phase I n=8 participants at risk BMS-911543 160 mg capsule by mouth twice daily	200 mg Phase I n=7 participants at risk BMS-911543 2000 mg capsule by mouth twice daily	240 mg Phase I n=3 participants at risk BMS-911543 240 mg capsule by mouth twice daily	120 mg Phase II n=22 participants at risk BMS-911543 120 mg capsule by mouth twice daily	200 mg Phase II n=20 participants at risk BMS-911543 200 mg capsule by mouth twice daily
Metabolism and nutrition disorders Decreased appetite	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	28.6% 2/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	10.0% 2/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Metabolism and nutrition disorders Hyperuricaemia	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	50.0% 2/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 2/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	9.1% 2/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	5.0% 1/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Blood and lymphatic system disorders Anaemia	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	75.0% 3/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	50.0% 2/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	100.0% 4/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	87.5% 7/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	57.1% 4/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	66.7% 2/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	77.3% 17/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	90.0% 18/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Blood and lymphatic system disorders Thrombocytopenia	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	50.0% 2/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	50.0% 4/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	28.6% 2/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	66.7% 2/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	13.6% 3/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	45.0% 9/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Blood and lymphatic system disorders Neutropenia	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	37.5% 3/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	14.3% 1/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	13.6% 3/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	20.0% 4/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Blood and lymphatic system disorders Leukopenia	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 2/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	15.0% 3/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Blood and lymphatic system disorders Spleen disorder	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	33.3% 1/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	9.1% 2/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
General disorders Fatigue	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	75.0% 3/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	75.0% 3/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	50.0% 2/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 2/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	71.4% 5/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	33.3% 1/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	13.6% 3/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	30.0% 6/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
General disorders Pyrexia	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	50.0% 2/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 2/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	28.6% 2/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	33.3% 1/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	18.2% 4/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	20.0% 4/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
General disorders Oedema	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	28.6% 2/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	66.7% 2/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	9.1% 2/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	10.0% 2/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
General disorders Chest pain	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	28.6% 2/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	13.6% 3/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	10.0% 2/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
General disorders Influenza like illness	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	66.7% 2/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	9.1% 2/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	10.0% 2/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
General disorders Early satiety	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 2/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	5.0% 1/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
General disorders Pain	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	15.0% 3/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
General disorders Chills	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	14.3% 1/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	33.3% 1/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	10.0% 2/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
General disorders Oedema peripheral	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	5.0% 1/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Gastrointestinal disorders Nausea	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	50.0% 2/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	50.0% 2/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	50.0% 2/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 2/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	57.1% 4/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	33.3% 1/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	27.3% 6/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	50.0% 10/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Gastrointestinal disorders Diarrhoea	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	75.0% 3/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	50.0% 2/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	50.0% 2/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	28.6% 2/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	31.8% 7/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	40.0% 8/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Gastrointestinal disorders Constipation	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	50.0% 2/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	50.0% 2/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	42.9% 3/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	33.3% 1/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	31.8% 7/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	20.0% 4/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Gastrointestinal disorders Abdominal Pain	50.0% 2/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	50.0% 2/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	14.3% 1/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	33.3% 1/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	31.8% 7/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Gastrointestinal disorders Vomiting	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	28.6% 2/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	33.3% 1/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	15.0% 3/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Gastrointestinal disorders Abdominal distension	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	18.2% 4/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	5.0% 1/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Gastrointestinal disorders Abdominal pain upper	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	50.0% 2/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	28.6% 2/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Respiratory, thoracic and mediastinal disorders Dyspnoea	50.0% 2/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	50.0% 2/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	50.0% 2/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 2/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	57.1% 4/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	33.3% 1/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	27.3% 6/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	30.0% 6/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	50.0% 2/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	42.9% 3/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	66.7% 2/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	9.1% 2/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 5/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	100.0% 3/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	18.2% 4/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 5/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Nervous system disorders Dizziness	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	42.9% 3/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	66.7% 2/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	45.5% 10/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	40.0% 8/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Nervous system disorders Headache	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	57.1% 4/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	13.6% 3/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	30.0% 6/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Nervous system disorders Neuropathy peripheral	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 2/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	28.6% 2/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	10.0% 2/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	14.3% 1/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	15.0% 3/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Nervous system disorders Paraesthesia	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	28.6% 2/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	10.0% 2/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Infections and infestations Upper respiratory tract infection	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	42.9% 3/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	13.6% 3/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	20.0% 4/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Infections and infestations Urinary tract infection	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	50.0% 2/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 2/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	33.3% 1/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	9.1% 2/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	10.0% 2/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Infections and infestations Sinusitis	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	14.3% 1/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	9.1% 2/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	5.0% 1/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Investigations Lipase increased	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	14.3% 1/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	33.3% 1/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	9.1% 2/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	35.0% 7/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Investigations Weight increased	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	50.0% 2/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	42.9% 3/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	13.6% 3/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	30.0% 6/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Investigations Alanine aminotransferase increased	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 2/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	13.6% 3/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	5.0% 1/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Metabolism and nutrition disorders Hyperkalaemia	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	13.6% 3/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	5.0% 1/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Investigations Aspartate aminotransferase increased	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 2/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	9.1% 2/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	5.0% 1/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Investigations Blood alkaline phosphatase increased	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	9.1% 2/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	10.0% 2/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Investigations Weight decreased	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	5.0% 1/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Investigations Amylase increased	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	33.3% 1/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	10.0% 2/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	57.1% 4/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	33.3% 1/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	31.8% 7/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	50.0% 10/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	42.9% 3/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	33.3% 1/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	22.7% 5/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	30.0% 6/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	14.3% 1/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	33.3% 1/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	9.1% 2/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	30.0% 6/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 2/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	28.6% 2/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	13.6% 3/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	20.0% 4/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	28.6% 2/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	66.7% 2/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	10.0% 2/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	28.6% 2/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	15.0% 3/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	14.3% 1/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	9.1% 2/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	15.0% 3/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Skin and subcutaneous tissue disorders Night sweats	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	50.0% 2/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	50.0% 2/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	28.6% 2/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	13.6% 3/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	15.0% 3/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Skin and subcutaneous tissue disorders Pain of skin	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	42.9% 3/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	33.3% 1/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	9.1% 2/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	20.0% 4/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Skin and subcutaneous tissue disorders Pruritus	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	22.7% 5/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	5.0% 1/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Skin and subcutaneous tissue disorders Rash	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	33.3% 1/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	20.0% 4/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	14.3% 1/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	13.6% 3/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	5.0% 1/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Metabolism and nutrition disorders Gout	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	14.3% 1/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	33.3% 1/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Injury, poisoning and procedural complications Contusion	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	50.0% 2/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	50.0% 2/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	50.0% 2/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	42.9% 3/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	66.7% 2/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	40.0% 8/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Injury, poisoning and procedural complications Fall	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	9.1% 2/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	10.0% 2/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Psychiatric disorders Insomnia	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 2/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	28.6% 2/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	9.1% 2/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 5/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Psychiatric disorders Anxiety	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 2/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	33.3% 1/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Vascular disorders Hypertension	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	14.3% 1/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	15.0% 3/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Vascular disorders Hypotension	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	33.3% 1/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Cardiac disorders Atrial fibrillation	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	25.0% 1/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	12.5% 1/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	14.3% 1/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	4.5% 1/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	5.0% 1/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)
Cardiac disorders Palpitations	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/4 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/8 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	0.00% 0/7 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	33.3% 1/3 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	13.6% 3/22 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)	5.0% 1/20 • From the date of subject's written consent until 30 days post discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time (approximately 4.5 years)

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Phone: Please email

Email: Clinical.Trials@bms.com

Results disclosure agreements

• Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
• Publication restrictions are in place

Restriction type: OTHER