Trial Outcomes & Findings for Study Of Letrozole With Or Without Palbociclib (PD-0332991) For The First-Line Treatment Of Hormone-Receptor Positive Advanced Breast Cancer (NCT NCT00721409)

NCT ID: NCT00721409

Last Updated: 2019-11-04

Results Overview

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 177 participants
• Primary outcome timeframe: Maximum treatment duration (approximately 55 months)
• Results posted on: 2019-11-04

Participant Flow

This Phase 1/2, open-label, randomized study enrolled a total of 12 participants at 3 sites in the United States for Phase 1. Phase 1 participants received Palbociclib + Letrozole. In Phase 2, a total of 165 participants were randomized (84 in palbociclib plus letrozole arm and 81 in letrozole alone arm) at 50 sites in 12 countries.

Phase 2 portion has 2 parts. Phase 2, Part 1 - ER positive, HER2 negative postmenopausal women with advanced breast cancer. Phase 2, Part 2- ER positive, HER2 negative postmenopausal women with tumors demonstrating CCND1 gene amplification and/or loss of CDKN2A gene.

Participant milestones

Measure	Phase 1 (Palbociclib + Letrozole) In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Palbociclib + Letrozole) All participants who were randomized to letrozole plus palbociclib in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. In Ph2P1 and Ph2P2, the participants received palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and letrozole 2.5 mg/d orally in a continuous regimen.	Phase 2 (Letrozole) All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.
Overall Study STARTED	12	84	81
Overall Study Treated	12	83	77
Overall Study COMPLETED	0	2	2
Overall Study NOT COMPLETED	12	82	79

Reasons for withdrawal

Measure	Phase 1 (Palbociclib + Letrozole) In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Palbociclib + Letrozole) All participants who were randomized to letrozole plus palbociclib in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. In Ph2P1 and Ph2P2, the participants received palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and letrozole 2.5 mg/d orally in a continuous regimen.	Phase 2 (Letrozole) All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.
Overall Study Global deterioration of health status	2	6	3
Overall Study Death	0	1	0
Overall Study Randomized not Treated	0	1	4
Overall Study Reason not specified	1	0	2
Overall Study Adverse Event	0	13	2
Overall Study Lost to Follow-up	0	0	1
Overall Study Withdrawal by Subject	1	6	5
Overall Study Objective progression or relapse	8	55	62

Baseline Characteristics

Study Of Letrozole With Or Without Palbociclib (PD-0332991) For The First-Line Treatment Of Hormone-Receptor Positive Advanced Breast Cancer

Baseline characteristics by cohort

Measure	Phase 1 (Palbociclib + Letrozole) n=12 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Palbociclib + Letrozole) n=84 Participants All participants who were randomized to letrozole plus palbociclib in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. In Ph2P1 and Ph2P2, the participants received palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and letrozole 2.5 mg/d orally in a continuous regimen.	Phase 2 (Letrozole) n=81 Participants All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Total n=177 Participants Total of all reporting groups
Age, Customized <18 Years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Customized 18-44 Years	1 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	7 Participants n=4 Participants
Age, Customized 45-64 Years	6 Participants n=5 Participants	45 Participants n=7 Participants	38 Participants n=5 Participants	89 Participants n=4 Participants
Age, Customized >= 65 Years	5 Participants n=5 Participants	37 Participants n=7 Participants	39 Participants n=5 Participants	81 Participants n=4 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	84 Participants n=7 Participants	81 Participants n=5 Participants	177 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
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
Race (NIH/OMB) Asian	0 Participants n=5 Participants	6 Participants n=7 Participants	4 Participants n=5 Participants	10 Participants n=4 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
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants	76 Participants n=7 Participants	72 Participants n=5 Participants	159 Participants n=4 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
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	6 Participants n=4 Participants

PRIMARY outcome

Timeframe: Maximum treatment duration (approximately 55 months)

Population: Safety analysis set included all participants who received at least 1 dose of any agent of the combination.

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

Outcome measures

Measure	Phase 1 (Palbociclib + Letrozole) n=12 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Letrozole) All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs; All Causalities) at Phase 1 Participants with AEs	12 Participants	—	—	—	—	—
Number of Participants With Treatment-Emergent Adverse Events (TEAEs; All Causalities) at Phase 1 Participants with SAEs	2 Participants	—	—	—	—	—
Number of Participants With Treatment-Emergent Adverse Events (TEAEs; All Causalities) at Phase 1 Participants with Grade 3 or 4 AEs	11 Participants	—	—	—	—	—
Number of Participants With Treatment-Emergent Adverse Events (TEAEs; All Causalities) at Phase 1 Participants with Grade 5 AEs	0 Participants	—	—	—	—	—

PRIMARY outcome

Timeframe: Maximum treatment duration (approximately 55 months)

Population: Safety analysis set included all participants who received at least 1 dose of any agent of the combination.

An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

Outcome measures

Measure	Phase 1 (Palbociclib + Letrozole) n=12 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Letrozole) All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Number of Participants With Treatment-Related Adverse Events at Phase 1 Participants with AEs	12 Participants	—	—	—	—	—
Number of Participants With Treatment-Related Adverse Events at Phase 1 Participants with SAEs	0 Participants	—	—	—	—	—
Number of Participants With Treatment-Related Adverse Events at Phase 1 Participants with Grade 3 or 4 AEs	11 Participants	—	—	—	—	—
Number of Participants With Treatment-Related Adverse Events at Phase 1 Participants with Grade 5 AEs	0 Participants	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 2 (4 weeks)

Population: Safety analysis set included all participants who received at least 1 dose of any agent of the combination.

Dose limiting toxicity was defined as any of the following TEAEs occurring during the second cycle of treatment and possibly attributable to the combination of letrozole plus Palbociclib: 1. Grade 4 hematologic toxicity (including platelets <25,000/μL, ANC <500/μL). 2. Grade 3 neutropenia associated with a documented infection or fever ≥38.5°C. 3. Grade ≥3 non-hematologic toxicities, except those that have not been maximally treated (eg, nausea, vomiting, diarrhea, hypertension). 4. Delay by ≥1 week in receiving the next scheduled dose of either study treatment due to persisting treatment-related toxicities (platelet count <50,000/μL; ANC <1,000/μL; nonhematologic toxicities of Grade ≥3 severity). 5. Inability to deliver at least 80% of the planned Palbociclib or letrozole doses during Cycle 2 due to toxicity possibly attributable to the study treatment.

Outcome measures

Measure	Phase 1 (Palbociclib + Letrozole) n=12 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Letrozole) All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Number of Participants With Dose Limiting Toxicities at Phase 1 Grade 4 Neutropenia	2 Participants	—	—	—	—	—
Number of Participants With Dose Limiting Toxicities at Phase 1 <80% of doses due to elevated creatinine	1 Participants	—	—	—	—	—

PRIMARY outcome

Timeframe: From randomization date to date of first documentation of progression or death (assessed up to 41 months)

Population: Intent-to-Treat (ITT) was used. This represented all randomized participants from Ph2P1 or Ph2P2 or Ph2P1+Ph2P2, where participants were classified according to the randomized treatment regardless of what treatment, if any, was received.

PFS was defined as the time from randomization (or the first dose of study treatment for non-randomized studies) to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. PFS calculated as (Weeks or Months) = (first event date minus randomization or the first dose date plus 1) divided by 7 (or 30.44 if in months). PFS is usually characterized by the median, 25% percentile,75% percentile and their 95% Confidence Intervals (CIs).

Outcome measures

Measure	Phase 1 (Palbociclib + Letrozole) n=84 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Letrozole) n=81 Participants All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) n=34 Participants All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) n=32 Participants Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) n=50 Participants Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) n=49 Participants Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Progression-Free Survival (PFS) at Phase 2 - Investigator Assessment	20.2 Months Interval 13.8 to 27.5	10.2 Months Interval 5.7 to 12.6	26.1 Months Interval 11.2 to Not reached	5.7 Months Interval 2.6 to 10.5	18.1 Months Interval 13.1 to 27.5	11.1 Months Interval 7.1 to 16.4

SECONDARY outcome

Timeframe: From Baseline up to end of study (assessed up to 55 months)

Population: Efficacy analysis set included all enrolled participants with the disease under study, adequate baseline disease assessment, and who started study treatment.

Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. Per RECIST v1.0: CR defined as disappearance of all target lesions and non-target lesions. PR defined as ≥30% decrease in sum of the longest diameters (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non target lesions.

Outcome measures

Measure	Phase 1 (Palbociclib + Letrozole) n=12 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Letrozole) All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Objective Response Rate - Percentage of Participants With Confirmed Objective Tumor Response at Phase 1	33.3 Percentage of participants Interval 9.9 to 65.1	—	—	—	—	—

SECONDARY outcome

Timeframe: From Baseline up to end of study (assessed up to 55 months)

Population: Efficacy analysis set included all enrolled participants with the disease under study, adequate baseline disease assessment, and who started study treatment.

CBR is defined as a confirmed CR, confirmed PR, or stable disease (SD) for at least 24 weeks on study according to RECIST. Confirmed responses are those that persisted on repeat imaging >= 4 weeks after initial response.

Outcome measures

Measure	Phase 1 (Palbociclib + Letrozole) n=12 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Letrozole) All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Percentage of Participants With Clinical Benefit Response (CBR) at Phase 1	83.3 Percentage of participants Interval 51.6 to 97.9	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 Day 14, and Cycle 2 Day 14

Population: The pharmacokinetic concentration set included all participants who were treated and had at least 1 concentration measurement in at least 1 pharmacokinetic assessment day. The pharmacokinetic parameter analysis set consisted of all participants treated who had at least 1 of the pharmacokinetic parameters of primary interest.

On Cycle 1 Day 14, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, 24, 48, 96 and 120 hours after Palbociclib dosing. On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing.

Outcome measures

Measure	Phase 1 (Palbociclib + Letrozole) n=12 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Letrozole) n=12 Participants All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC24) at Phase 1	1982 ng·hr/mL Geometric Coefficient of Variation 29	1933 ng·hr/mL Geometric Coefficient of Variation 31	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 Day 14, and Cycle 2 Day 14

Population: The pharmacokinetic concentration set included all participants who were treated and had at least 1 concentration measurement in at least 1 pharmacokinetic assessment day. The pharmacokinetic parameter analysis set consisted of all participants treated who had at least 1 of the pharmacokinetic parameters of primary interest.

On Cycle 1 Day 14, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, 24, 48, 96 and 120 hours after Palbociclib dosing. On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing.

Outcome measures

Measure	Phase 1 (Palbociclib + Letrozole) n=12 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Letrozole) n=12 Participants All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Maximum Observed Plasma Concentration (Cmax) at Phase 1	115.8 ng/mL Geometric Coefficient of Variation 28	108.4 ng/mL Geometric Coefficient of Variation 29	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 Day 14, and Cycle 2 Day 14

Population: The pharmacokinetic concentration set included all participants who were treated and had at least 1 concentration measurement in at least 1 pharmacokinetic assessment day. The pharmacokinetic parameter analysis set consisted of all participants treated who had at least 1 of the pharmacokinetic parameters of primary interest.

On Cycle 1 Day 14, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, 24, 48, 96 and 120 hours after Palbociclib dosing. On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing.

Outcome measures

Measure	Phase 1 (Palbociclib + Letrozole) n=12 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Letrozole) n=12 Participants All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Time to Maximum Plasma Concentration (Tmax) at Phase 1	7.92 Hour Full Range 28 • Interval 2.17 to 8.2	7.92 Hour Full Range 29 • Interval 2.0 to 8.08	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 Day 14, and Cycle 2 Day 14

Population: The pharmacokinetic concentration set included all participants who were treated and had at least 1 concentration measurement in at least 1 pharmacokinetic assessment day. The pharmacokinetic parameter analysis set consisted of all participants treated who had at least 1 of the pharmacokinetic parameters of primary interest.

On Cycle 1 Day 14, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, 24, 48, 96 and 120 hours after Palbociclib dosing. On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing.

Outcome measures

Measure	Phase 1 (Palbociclib + Letrozole) n=12 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Letrozole) n=12 Participants All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Terminal Plasma Half-life (t1/2) at Phase 1	28.81 Hour Standard Deviation 5.0462 • Interval 2.17 to 8.2	NA Hour Standard Deviation NA • Interval 2.0 to 8.08 Not calculated	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 Day 14, and Cycle 2 Day 14

Population: The pharmacokinetic concentration set included all participants who were treated and had at least 1 concentration measurement in at least 1 pharmacokinetic assessment day. The pharmacokinetic parameter analysis set consisted of all participants treated who had at least 1 of the pharmacokinetic parameters of primary interest.

On Cycle 1 Day 14, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, 24, 48, 96 and 120 hours after Palbociclib dosing. On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing.

Outcome measures

Measure	Phase 1 (Palbociclib + Letrozole) n=12 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Letrozole) n=12 Participants All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Apparent Clearance (CL/F) at Phase 1	63.08 L/hr Geometric Coefficient of Variation 29 • Interval 2.17 to 8.2	NA L/hr Geometric Coefficient of Variation NA • Interval 2.0 to 8.08 Not calculated	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 Day 14, and Cycle 2 Day 14

Population: The pharmacokinetic concentration set included all participants who were treated and had at least 1 concentration measurement in at least 1 pharmacokinetic assessment day. The pharmacokinetic parameter analysis set consisted of all participants treated who had at least 1 of the pharmacokinetic parameters of primary interest.

On Cycle 1 Day 14, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, 24, 48, 96 and 120 hours after Palbociclib dosing. On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing.

Outcome measures

Measure	Phase 1 (Palbociclib + Letrozole) n=12 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Letrozole) n=12 Participants All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Apparent Volume of Distribution (Vz/F) at Phase 1	2583 L Geometric Coefficient of Variation 26 • Interval 2.17 to 8.2	NA L Geometric Coefficient of Variation NA • Interval 2.0 to 8.08 Not calculated	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 2 Day 14, Cycle 2 Day 28

Population: The pharmacokinetic concentration set included all participants who were treated and had at least 1 concentration measurement in at least 1 pharmacokinetic assessment day. The pharmacokinetic parameter analysis set consisted of all participants treated who had at least 1 of the pharmacokinetic parameters of primary interest.

On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing. On Cycle 2 Day 28, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, and 24 hours after letrozole dosing.

Outcome measures

Measure	Phase 1 (Palbociclib + Letrozole) n=12 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Letrozole) n=12 Participants All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Summary of Plasma Letrozole Pharmacokinetic Parameter Following Letrozole Alone and in Combination With Palbociclib: AUC24 at Phase 1	1739 ng·hr/mL Geometric Coefficient of Variation 30 • Interval 2.17 to 8.2	1936 ng·hr/mL Geometric Coefficient of Variation 35 • Interval 2.0 to 8.08	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 2 Day 14, and Cycle 2 Day 28

Population: The pharmacokinetic concentration set included all participants who were treated and had at least 1 concentration measurement in at least 1 pharmacokinetic assessment day. The pharmacokinetic parameter analysis set consisted of all participants treated who had at least 1 of the pharmacokinetic parameters of primary interest.

On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing. On Cycle 2 Day 28, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, and 24 hours after letrozole dosing.

Outcome measures

Measure	Phase 1 (Palbociclib + Letrozole) n=12 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Letrozole) n=12 Participants All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Summary of Plasma Letrozole Pharmacokinetic Parameter Following Letrozole Alone and in Combination With Palbociclib: Cmax at Phase 1	94.95 ng/mL Geometric Coefficient of Variation 27 • Interval 2.17 to 8.2	104.0 ng/mL Geometric Coefficient of Variation 31 • Interval 2.0 to 8.08	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 2 Day 14, and Cycle 2 Day 28

Population: The pharmacokinetic concentration set included all participants who were treated and had at least 1 concentration measurement in at least 1 pharmacokinetic assessment day. The pharmacokinetic parameter analysis set consisted of all participants treated who had at least 1 of the pharmacokinetic parameters of primary interest.

On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing. On Cycle 2 Day 28, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, and 24 hours after letrozole dosing.

Outcome measures

Measure	Phase 1 (Palbociclib + Letrozole) n=12 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Letrozole) n=12 Participants All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Summary of Plasma Letrozole Pharmacokinetic Parameter Following Letrozole Alone and in Combination With Palbociclib: Tmax at Phase 1	2.00 Hour Full Range 27 • Interval 0.833 to 4.13	1.04 Hour Full Range 31 • Interval 0.0 to 4.42	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 Day 1 prior to dosing, Cycle 1 Day 14 (2, 4 [prior to meal], 8, 24, 48, and 96 hours after dosing of Palbociclib), Cycle 2 Day 1 and Day 14 (prior to and 4 hours after dosing of letrozole)

Population: Safety analysis set included all participants who received at least 1 dose of any agent of the combination.

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR), by Bazette's formula (QTcB = QT divided by square root of RR) and corrected QT interval according to study-specific criteria (QTcS). Participants with maximum increase from baseline of 30 to less than (<) 60 msec(borderline) and greater than or equal to (>=) 60 msec (prolonged) were summarized.

Outcome measures

Measure	Phase 1 (Palbociclib + Letrozole) n=12 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Letrozole) All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Number of Participants With Increase From Baseline in Corrected QT (QTc) Interval at Phase 1 QTcB - Change <30	9 Participants	—	—	—	—	—
Number of Participants With Increase From Baseline in Corrected QT (QTc) Interval at Phase 1 QTcB - 30 ≤ change <60	3 Participants	—	—	—	—	—
Number of Participants With Increase From Baseline in Corrected QT (QTc) Interval at Phase 1 QTcB - Change ≥60	0 Participants	—	—	—	—	—
Number of Participants With Increase From Baseline in Corrected QT (QTc) Interval at Phase 1 QTcF - Change <30	11 Participants	—	—	—	—	—
Number of Participants With Increase From Baseline in Corrected QT (QTc) Interval at Phase 1 QTcF - 30 ≤ change <60	1 Participants	—	—	—	—	—
Number of Participants With Increase From Baseline in Corrected QT (QTc) Interval at Phase 1 QTcF - Change ≥60	0 Participants	—	—	—	—	—
Number of Participants With Increase From Baseline in Corrected QT (QTc) Interval at Phase 1 QTcS - Change <30	8 Participants	—	—	—	—	—
Number of Participants With Increase From Baseline in Corrected QT (QTc) Interval at Phase 1 QTcS - 30 ≤ change <60	4 Participants	—	—	—	—	—
Number of Participants With Increase From Baseline in Corrected QT (QTc) Interval at Phase 1 QTcS - Change ≥60	0 Participants	—	—	—	—	—

SECONDARY outcome

Timeframe: From randomization until death (assessed up to 86 months)

Population: ITT was used. This represented all randomized participants from Ph2P1or Ph2P2 or Ph2P1+Ph2P2, where participants were classified according to the randomized treatment regardless of what treatment, if any, was received.

Time in weeks or months from randomization to date of death due to any cause. OS was calculated as (the death date or last known alive date (if death date unavailable) minus the date of randomization plus 1) divided by 7 or 30.44 if in months.

Outcome measures

Measure	Phase 1 (Palbociclib + Letrozole) n=84 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Letrozole) n=81 Participants All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) n=34 Participants All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) n=32 Participants Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) n=50 Participants Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) n=49 Participants Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Overall Survival (OS) at Phase 2	37.5 Months Interval 31.4 to 47.8	34.5 Months Interval 27.4 to 42.6	37.5 Months Interval 27.6 to 58.8	33.3 Months Interval 26.0 to 54.3	35.1 Months Interval 28.1 to 47.8	35.7 Months Interval 26.6 to 46.7

SECONDARY outcome

Timeframe: From randomization up to the end of treatment (approximately 41 months)

Population: ITT was used. This represented all randomized participants from Ph2P1or Ph2P2 or Ph2P1+Ph2P2, where participants were classified according to the randomized treatment regardless of what treatment, if any, was received.

Percentage of participants with objective response based assessment of confirmed CR or confirmed PR according to RECIST. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. Per RECIST v1.0: CR defined as disappearance of all target lesions and non-target lesions. PR defined as ≥30% decrease in sum of the longest diameters (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non target lesions.

Outcome measures

Measure	Phase 1 (Palbociclib + Letrozole) n=84 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Letrozole) n=81 Participants All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) n=34 Participants All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) n=32 Participants Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) n=50 Participants Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) n=49 Participants Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Objective Response Rate - Percentage of Participants With Confirmed Objective Response at Phase 2- Investigator Assessment	42.9 Percentage of participants Interval 32.1 to 54.1	33.3 Percentage of participants Interval 23.2 to 44.7	44.1 Percentage of participants Interval 27.2 to 62.1	25.0 Percentage of participants Interval 11.5 to 43.4	42.0 Percentage of participants Interval 28.2 to 56.8	38.8 Percentage of participants Interval 25.2 to 53.8

SECONDARY outcome

Timeframe: From randomization up to the end of treatment (approximately 41 months)

Population: Participants in ITT population with measurable disease were used.

Percentage of participants with objective response based assessment of confirmed CR or PR according to RECIST. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. Per RECIST v1.0: CR defined as disappearance of all target lesions and non-target lesions. PR defined as ≥30% decrease in sum of the LD of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non target lesions. Measurable disease referred to the lesions that was accurately measured in at least 1 dimension (longest diameter to be recorded) as ≥20 mm with conventional techniques or as ≥10-16 mm with spiral computer tomography scan (depending on reconstruction interval). Clinical lesions were only be considered measurable when they were superficial (eg, skin nodules, palpable lymph nodes).

Outcome measures

Measure	Phase 1 (Palbociclib + Letrozole) n=65 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Letrozole) n=66 Participants All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) n=27 Participants All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) n=23 Participants Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) n=21 Participants Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) n=43 Participants Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Objective Response Rate - Percentage of Participants With Confirmed Objective Response in Participants With Measurable Disease at Phase 2- Investigator Assessment	55.4 Percentage of participants Interval 42.5 to 67.7	39.4 Percentage of participants Interval 27.6 to 52.2	55.6 Percentage of participants Interval 35.3 to 74.5	34.8 Percentage of participants Interval 16.4 to 57.3	55.3 Percentage of participants Interval 38.3 to 71.4	41.9 Percentage of participants Interval 27.0 to 57.9

SECONDARY outcome

Timeframe: From randomization up to the end of treatment (approximately 41 months)

Population: A subset of ITT population i.e., participants who had response was used for this analysis.

Time in weeks, (months or years) from randomization or (start of study treatment for non-randomized studies) to first documentation of objective tumor progression. TTP was calculated as (first event date or last known progression-free date minus the date of randomization [or first dose of study medication for non-randomized studies] plus 1) divided by 7 or 30.44 if in months. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD] per RECIST).

Outcome measures

Measure	Phase 1 (Palbociclib + Letrozole) n=36 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Letrozole) n=27 Participants All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) n=15 Participants All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) n=8 Participants Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) n=21 Participants Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) n=19 Participants Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Duration of Response at Phase 2 - Investigator Assessment	20.3 Months Interval 13.4 to 25.8	11.1 Months Interval 9.3 to 31.6	20.9 Months Interval 6.2 to 25.8	10.8 Months Interval 3.7 to 31.6	20.2 Months Interval 13.0 to Not reached	14.8 Months Interval 7.4 to Not reached

SECONDARY outcome

Timeframe: From randomization up to the end of treatment (approximately 41 months)

Population: ITT was used. This represented all randomized patients from Ph2P1or Ph2P2 or Ph2P1+Ph2P2, where participants were classified according to the randomized treatment regardless of what treatment, if any, was received.

CBR is defined as a confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD) for at least 24 weeks on study according to RECIST.

Outcome measures

Measure	Phase 1 (Palbociclib + Letrozole) n=84 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Letrozole) n=81 Participants All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) n=34 Participants All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) n=32 Participants Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) n=50 Participants Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) n=49 Participants Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Number of Participants With CBR at Phase 2 - Investigator Assessment	81.0 Percentage of participants Interval 70.9 to 88.7	58.0 Percentage of participants Interval 46.5 to 68.9	76.5 Percentage of participants Interval 58.8 to 89.3	43.8 Percentage of participants Interval 26.4 to 62.3	84.0 Percentage of participants Interval 70.9 to 92.8	67.3 Percentage of participants Interval 52.5 to 80.1

SECONDARY outcome

Timeframe: From randomization up to the end of treatment (approximately 41 months)

Population: ITT was used. This represented all randomized participants from Ph2P1or Ph2P2 or Ph2P1+Ph2P2, where participants were classified according to the randomized treatment regardless of what treatment, if any, was received.

Time in weeks, (months or years) from randomization or (start of study treatment for non-randomized studies) to first documentation of objective tumor progression. TTP was calculated as (first event date or last known progression-free date minus the date of randomization [or first dose of study medication for non-randomized studies] plus 1) divided by 7 or 30.44 if in months. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD] per RECIST).

Outcome measures

Measure	Phase 1 (Palbociclib + Letrozole) n=84 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Letrozole) n=81 Participants All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) n=34 Participants All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) n=32 Participants Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) n=50 Participants Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) n=49 Participants Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Time to Tumor Progression (TTP) at Phase 2-Investigator Assessment	20.2 Months Interval 13.8 to 27.5	10.2 Months Interval 5.7 to 12.6	26.1 Months Interval 11.2 to Not reached	5.7 Months Interval 2.6 to 10.5	18.8 Months Interval 13.1 to 27.5	11.1 Months Interval 7.1 to 16.4

SECONDARY outcome

Timeframe: Baseline, End of treatment (approximately 41 months)

Population: Patient reported outcome evaluable participants included participants who had received at least 1 dose of study medication, had baseline data, and at least one post-baseline measurement.

The mBPI-sf is a validated and reliable self-report questionnaire which consists of 13 questions that assess the severity and impact of pain on daily function. The 13 items of the questionnaire make up two scales and two single items. The scales include the 4-item Pain Severity Scale (worst pain, least pain, average pain, and pain right now) and the 7-item Pain Interference Scale (general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life). Each item of the pain severity and pain interference scales are based on a 11-point numeric rating scale from 0 ("no pain" or "does not interfere") to 10 ("pain as bad as you can imagine" or "completely interferes").

Outcome measures

Measure	Phase 1 (Palbociclib + Letrozole) n=76 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Letrozole) n=74 Participants All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) n=29 Participants All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) n=27 Participants Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) n=47 Participants Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) n=47 Participants Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Change From Baseline in Modified Brief Pain Inventory in Pain Severity Scale (mBPI-sf) Questionnaire at Phase 2 Pain at its worst in the last 24 hours	0.6 Units on a scale Standard Error 0.42 • Interval 28.4 to	0.1 Units on a scale Standard Error 0.42 • Interval 26.4 to	0.2 Units on a scale Standard Error 0.60 • Interval 27.6 to	0.0 Units on a scale Standard Error 0.89 • Interval 26.0 to	1.2 Units on a scale Standard Error 0.55 • Interval 26.0 to	0.1 Units on a scale Standard Error 0.43 • Interval 23.4 to
Change From Baseline in Modified Brief Pain Inventory in Pain Severity Scale (mBPI-sf) Questionnaire at Phase 2 Pain at its least in the last 24 hours	0.4 Units on a scale Standard Error 0.27	0.4 Units on a scale Standard Error 0.27	0.3 Units on a scale Standard Error 0.31	0.7 Units on a scale Standard Error 0.50	0.5 Units on a scale Standard Error 0.40	0.2 Units on a scale Standard Error 0.31
Change From Baseline in Modified Brief Pain Inventory in Pain Severity Scale (mBPI-sf) Questionnaire at Phase 2 Pain on the average	0.2 Units on a scale Standard Error 0.33	0.2 Units on a scale Standard Error 0.34	-0.1 Units on a scale Standard Error 0.48	0.2 Units on a scale Standard Error 0.64	0.4 Units on a scale Standard Error 0.45	0.3 Units on a scale Standard Error 0.40
Change From Baseline in Modified Brief Pain Inventory in Pain Severity Scale (mBPI-sf) Questionnaire at Phase 2 Pain right now	0.3 Units on a scale Standard Error 0.35	0.1 Units on a scale Standard Error 0.36	0.1 Units on a scale Standard Error 0.31	0.3 Units on a scale Standard Error 0.66	0.3 Units on a scale Standard Error 0.55	0.0 Units on a scale Standard Error 0.43
Change From Baseline in Modified Brief Pain Inventory in Pain Severity Scale (mBPI-sf) Questionnaire at Phase 2 Pain Severity Scale	0.4 Units on a scale Standard Error 0.29	0.2 Units on a scale Standard Error 0.32	0.0 Units on a scale Standard Error 0.36	0.3 Units on a scale Standard Error 0.62	0.6 Units on a scale Standard Error 0.41	0.1 Units on a scale Standard Error 0.36

SECONDARY outcome

Timeframe: Baseline, End of treatment (approximately 41 months)

Population: Patient reported outcome evaluable participants included participants who had received at least 1 dose of study medication, had baseline data, and at least one post-baseline measurement.

The mBPI-sf is a validated and reliable self-report questionnaire which consists of 13 questions that assess the severity and impact of pain on daily function. The 13 items of the questionnaire make up two scales and two single items. The scales include the 4-item Pain Severity Scale (worst pain, least pain, average pain, and pain right now) and the 7-item Pain Interference Scale (general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life). Each item of the pain severity and pain interference scales are based on a 11-point numeric rating scale from 0 ("no pain" or "does not interfere") to 10 ("pain as bad as you can imagine" or "completely interferes").

Outcome measures

Measure	Phase 1 (Palbociclib + Letrozole) n=76 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Letrozole) n=74 Participants All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) n=29 Participants All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) n=27 Participants Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) n=47 Participants Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) n=47 Participants Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Change From Baseline in Modified Brief Pain Inventory in Pain Interference Scale (mBPI-sf) Questionnaire at Phase 2 General Activity	1.1 Units on a scale Standard Error 0.40 • Interval 28.4 to	0.2 Units on a scale Standard Error 0.31 • Interval 26.4 to	1.0 Units on a scale Standard Error 0.66 • Interval 27.6 to	0.2 Units on a scale Standard Error 0.58 • Interval 26.0 to	1.2 Units on a scale Standard Error 0.51 • Interval 26.0 to	0.3 Units on a scale Standard Error 0.37 • Interval 23.4 to
Change From Baseline in Modified Brief Pain Inventory in Pain Interference Scale (mBPI-sf) Questionnaire at Phase 2 Mood	0.8 Units on a scale Standard Error 0.50	0.2 Units on a scale Standard Error 0.36	0.6 Units on a scale Standard Error 0.72	-0.2 Units on a scale Standard Error 0.62	1.0 Units on a scale Standard Error 0.69	0.4 Units on a scale Standard Error 0.44
Change From Baseline in Modified Brief Pain Inventory in Pain Interference Scale (mBPI-sf) Questionnaire at Phase 2 Walking ability	0.8 Units on a scale Standard Error 0.46	0.1 Units on a scale Standard Error 0.35	1.0 Units on a scale Standard Error 0.55	0.3 Units on a scale Standard Error 0.63	0.7 Units on a scale Standard Error 0.67	0.0 Units on a scale Standard Error 0.43
Change From Baseline in Modified Brief Pain Inventory in Pain Interference Scale (mBPI-sf) Questionnaire at Phase 2 Normal work	0.7 Units on a scale Standard Error 0.48	0.3 Units on a scale Standard Error 0.39	1.0 Units on a scale Standard Error 0.53	0.2 Units on a scale Standard Error 0.74	0.5 Units on a scale Standard Error 0.71	0.4 Units on a scale Standard Error 0.45
Change From Baseline in Modified Brief Pain Inventory in Pain Interference Scale (mBPI-sf) Questionnaire at Phase 2 Relations	0.8 Units on a scale Standard Error 0.32	0.8 Units on a scale Standard Error 0.32	0.6 Units on a scale Standard Error 0.34	0.6 Units on a scale Standard Error 0.60	0.9 Units on a scale Standard Error 0.47	0.8 Units on a scale Standard Error 0.37
Change From Baseline in Modified Brief Pain Inventory in Pain Interference Scale (mBPI-sf) Questionnaire at Phase 2 Sleep	0.6 Units on a scale Standard Error 0.43	0.3 Units on a scale Standard Error 0.35	0.1 Units on a scale Standard Error 0.53	0.5 Units on a scale Standard Error 0.63	0.9 Units on a scale Standard Error 0.61	0.1 Units on a scale Standard Error 0.42
Change From Baseline in Modified Brief Pain Inventory in Pain Interference Scale (mBPI-sf) Questionnaire at Phase 2 Enjoyment of life	0.8 Units on a scale Standard Error 0.46	0.6 Units on a scale Standard Error 0.41	0.4 Units on a scale Standard Error 0.34	0.2 Units on a scale Standard Error 0.69	1.1 Units on a scale Standard Error 0.71	0.8 Units on a scale Standard Error 0.52
Change From Baseline in Modified Brief Pain Inventory in Pain Interference Scale (mBPI-sf) Questionnaire at Phase 2 Pain Interference Scale	0.8 Units on a scale Standard Error 0.34	0.4 Units on a scale Standard Error 0.30	0.7 Units on a scale Standard Error 0.42	0.3 Units on a scale Standard Error 0.56	0.9 Units on a scale Standard Error 0.48	0.4 Units on a scale Standard Error 0.36

SECONDARY outcome

Timeframe: Screening visit (≤ 28 Days prior to dosing)

Population: Copy number analysis set included participants in the Safety Analysis Set who had at least 1 of the biomarker assessments.

Tissue samples were used for retrospective biomarker analyses. For Phase 2 Part 2, the tissue samples were sent to a central laboratory for the assessment of participant selection biomarkers. For Phase 2 Part 1, the assessment of the biomarkers (CCND1 amplification and/or loss of p16) were performed retrospectively from the available samples.

Outcome measures

Measure	Phase 1 (Palbociclib + Letrozole) n=22 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Letrozole) n=24 Participants All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) n=50 Participants All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) n=48 Participants Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Presence or Absence of Tumor Tissue Biomarkers at Phase 2 - p16/INK4A, CCND1 CCND1>=1.5	12 Participants 0.66 • Interval 27.6 to	9 Participants 0.58 • Interval 26.0 to	39 Participants 0.51 • Interval 26.0 to	44 Participants 0.37 • Interval 23.4 to	—	—
Presence or Absence of Tumor Tissue Biomarkers at Phase 2 - p16/INK4A, CCND1 p16/INK4A<0.8	0 Participants 0.72	2 Participants 0.62	19 Participants 0.69	12 Participants 0.44	—	—
Presence or Absence of Tumor Tissue Biomarkers at Phase 2 - p16/INK4A, CCND1 CCND1>=1.5 and p16/INK4A<0.8	0 Participants 0.55	2 Participants 0.63	8 Participants 0.67	8 Participants 0.43	—	—

SECONDARY outcome

Timeframe: Screening visit (≤ 28 Days prior to dosing)

Population: All participants in the Safety Analysis set who had a Ki67 protein biomarker assessment.

Frequency of tumor tissue biomarker Ki67 was evaluated in across treatment groups.

Outcome measures

Measure	Phase 1 (Palbociclib + Letrozole) n=74 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Letrozole) n=71 Participants All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) n=24 Participants All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) n=26 Participants Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) n=50 Participants Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) n=45 Participants Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Presence or Absence of Tumor Tissue Biomarkers at Phase 2 - Ki67 <=20%	26 Participants 0.40 • Interval 28.4 to	31 Participants 0.31 • Interval 26.4 to	7 Participants 0.66 • Interval 27.6 to	16 Participants 0.58 • Interval 26.0 to	19 Participants 0.51 • Interval 26.0 to	15 Participants 0.37 • Interval 23.4 to
Presence or Absence of Tumor Tissue Biomarkers at Phase 2 - Ki67 >20%	48 Participants 0.50	40 Participants 0.36	17 Participants 0.72	10 Participants 0.62	31 Participants 0.69	30 Participants 0.44

SECONDARY outcome

Timeframe: Screening visit (≤ 28 Days prior to dosing)

Population: Protein biomarkers analysis set included all participants in the safety analysis set who had at least protein biomarker assessment.

Presence or absence of tumor RB and CyclinD1 were evaluated. The following definitions of expression applied in the below table: Positive: any expression >0 and Negative: any expression=0.

Outcome measures

Measure	Phase 1 (Palbociclib + Letrozole) n=45 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Letrozole) n=35 Participants All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) n=12 Participants All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) n=16 Participants Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) n=33 Participants Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) n=19 Participants Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Presence or Absence of Tumor Tissue Biomarkers at Phase 2 - Tumor Retinoblastoma (RB) and CyclinD1 RB - Negative	2 Participants	2 Participants	2 Participants	0 Participants	0 Participants	2 Participants
Presence or Absence of Tumor Tissue Biomarkers at Phase 2 - Tumor Retinoblastoma (RB) and CyclinD1 CyclinD1 - Positive	41 Participants 0.40 • Interval 28.4 to	32 Participants 0.31 • Interval 26.4 to	10 Participants 0.66 • Interval 27.6 to	16 Participants 0.58 • Interval 26.0 to	31 Participants 0.51 • Interval 26.0 to	16 Participants 0.37 • Interval 23.4 to
Presence or Absence of Tumor Tissue Biomarkers at Phase 2 - Tumor Retinoblastoma (RB) and CyclinD1 CyclinD1 - Negative	3 Participants 0.50	3 Participants 0.36	2 Participants 0.72	0 Participants 0.62	1 Participants 0.69	3 Participants 0.44
Presence or Absence of Tumor Tissue Biomarkers at Phase 2 - Tumor Retinoblastoma (RB) and CyclinD1 RB - Positive	41 Participants	32 Participants	10 Participants	16 Participants	31 Participants	16 Participants

SECONDARY outcome

Timeframe: Screening visit (≤ 28 Days prior to dosing)

Population: Copy number analysis set included participants in the Safety Analysis Set who had at least 1 of the biomarker assessments.

Gene copy number for CCND1 (CCND1/CEP11) and p16/INK4A (p16/CEP9) were evaluated. This analysis was done for Phase 2 combined group.

Outcome measures

Measure	Phase 1 (Palbociclib + Letrozole) n=72 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Letrozole) n=72 Participants All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Summary of Copy Number for CCND1 (CCND1/CEP11) and p16/INK4A (p16/CEP9) at Phase 2 CCND1	2.76 Copy number Standard Deviation 1.875 • Interval 28.4 to	2.73 Copy number Standard Deviation 1.559 • Interval 26.4 to	—	—	—	—
Summary of Copy Number for CCND1 (CCND1/CEP11) and p16/INK4A (p16/CEP9) at Phase 2 p16/INK4A	0.83 Copy number Standard Deviation 0.224	0.87 Copy number Standard Deviation 0.173	—	—	—	—

SECONDARY outcome

Timeframe: Screening visit (≤ 28 Days prior to dosing)

Population: Polymorphism analysis set included participants in the safety analysis set who had at least 1 polymorphism assessment.

One 2-mL blood specimen was collected for the analysis of germline polymorphism in CYP19A1 and CCND1 genes. A single nucleotide polymorphism (SNP) rs4646 as defined in the National Center for Biotechnology Information (NCBI) database in the aromatase gene (CYP19A1) was analyzed. A germline polymorphism G/A870 (rs9344) in the CCND1 gene was analyzed.

Outcome measures

Measure	Phase 1 (Palbociclib + Letrozole) n=76 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Letrozole) n=74 Participants All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) n=30 Participants All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) n=28 Participants Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) n=46 Participants Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) n=46 Participants Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Percentage of Participants With Tumor Expression of CYP19A1 and CCND1 Genotypes at Phase 2 CYP19A1 - A/A Genotype	7.9 Percentage of participants 0.42 • Interval 28.4 to	5.4 Percentage of participants 0.42 • Interval 26.4 to	10.0 Percentage of participants 0.60 • Interval 27.6 to	10.7 Percentage of participants 0.89 • Interval 26.0 to	6.5 Percentage of participants 0.55 • Interval 26.0 to	2.2 Percentage of participants 0.43 • Interval 23.4 to
Percentage of Participants With Tumor Expression of CYP19A1 and CCND1 Genotypes at Phase 2 CYP19A1 - C/A Genotype	34.2 Percentage of participants 0.27	36.5 Percentage of participants 0.27	33.3 Percentage of participants 0.31	42.9 Percentage of participants 0.50	34.8 Percentage of participants 0.40	32.6 Percentage of participants 0.31
Percentage of Participants With Tumor Expression of CYP19A1 and CCND1 Genotypes at Phase 2 CYP19A1 - C/C Genotype	57.9 Percentage of participants 0.33	58.1 Percentage of participants 0.34	56.7 Percentage of participants 0.48	46.4 Percentage of participants 0.64	58.7 Percentage of participants 0.45	65.2 Percentage of participants 0.40
Percentage of Participants With Tumor Expression of CYP19A1 and CCND1 Genotypes at Phase 2 CCND1 - A/A Genotype	26.3 Percentage of participants 0.35	28.4 Percentage of participants 0.36	33.3 Percentage of participants 0.31	39.3 Percentage of participants 0.66	21.7 Percentage of participants 0.55	21.7 Percentage of participants 0.43
Percentage of Participants With Tumor Expression of CYP19A1 and CCND1 Genotypes at Phase 2 CCND1 - G/A Genotype	47.4 Percentage of participants 0.29	47.3 Percentage of participants 0.32	43.3 Percentage of participants 0.36	42.9 Percentage of participants 0.62	50.0 Percentage of participants 0.41	50.0 Percentage of participants 0.36
Percentage of Participants With Tumor Expression of CYP19A1 and CCND1 Genotypes at Phase 2 CCND1 - G/G Genotype	26.3 Percentage of participants	24.3 Percentage of participants	23.3 Percentage of participants	17.9 Percentage of participants	28.3 Percentage of participants	28.3 Percentage of participants

SECONDARY outcome

Timeframe: Baseline up to 28 days after last dose of study drug (for a maximum of 86 months)

Population: All treated as treated set included all treated participants classified by the treatment actually received.

AE:any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship.AEs included both serious and non-serious AEs.SAE:AE resulting in any of following outcomes/deemed significant and jeopardized participants or required treatment to prevent other AE outcomes for any other reason:death;initial or prolonged inpatient hospitalization;life-threatening experience (immediate risk of dying);persistent or significant disability/incapacity;congenital anomaly.Treatment emergent AEs:events occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or worsened relative to pre-treatment state.AEs were graded as per the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 and coded using Medical Dictionary for Regulatory Activities (MedDRA). Participants with AE of grade 3 or 4 and grade 5 were reported as Grade 3:Severe, Grade 4:Life threatening, Grade 5:Death related to AE.

Outcome measures

Measure	Phase 1 (Palbociclib + Letrozole) n=83 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Letrozole) n=77 Participants All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) n=33 Participants All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) n=29 Participants Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) n=50 Participants Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) n=48 Participants Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Number of Participants With TEAEs (All Causalities) at Phase 2 Participants with AEs	83 Participants	66 Participants	33 Participants	25 Participants	50 Participants	41 Participants
Number of Participants With TEAEs (All Causalities) at Phase 2 Participants with SAEs	22 Participants	6 Participants	10 Participants	2 Participants	12 Participants	4 Participants
Number of Participants With TEAEs (All Causalities) at Phase 2 Participants with Grade 3 or 4 AEs	70 Participants	19 Participants	29 Participants	5 Participants	41 Participants	14 Participants
Number of Participants With TEAEs (All Causalities) at Phase 2 Participants with Grade 5 AEs	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline up to 28 days after last dose of study drug (for a maximum of 86 months)

Population: All treated as treated set included all treated participants classified by the treatment actually received.

AE: any untoward medical occurrence in a participant who received study drug. AEs included both serious and non-serious adverse events. SAE: AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment emergent AEs: events occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. Treatment related AEs: all AEs with causality related to treatment. Relatedness to drug was assessed by the investigator. AEs were graded according to the CTCAE version 3.0 and coded using the MedDRA. Number of participants with AE of grade 3 or 4 and with AE of grade 5 were reported as Grade 3: Severe, Grade 4: Life threatening, Grade 5: Death related to AE.

Outcome measures

Measure	Phase 1 (Palbociclib + Letrozole) n=83 Participants In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Letrozole) n=77 Participants All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) n=33 Participants All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) n=29 Participants Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) n=50 Participants Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) n=48 Participants Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Number of Participants With Treatment-Related Adverse Events at Phase 2 Participants with Grade 3 or 4 AEs	57 Participants	2 Participants	25 Participants	0 Participants	32 Participants	2 Participants
Number of Participants With Treatment-Related Adverse Events at Phase 2 Participants with Grade 5 AEs	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-Related Adverse Events at Phase 2 Participants with AEs	78 Participants	33 Participants	32 Participants	13 Participants	46 Participants	20 Participants
Number of Participants With Treatment-Related Adverse Events at Phase 2 Participants with SAEs	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants

Adverse Events

Phase 1 (Palbociclib + Letrozole)

Serious events: 2 serious events

Other events: 12 other events

Deaths: 0 deaths

Phase 2 (Palbociclib + Letrozole)

Serious events: 22 serious events

Other events: 83 other events

Deaths: 3 deaths

Phase 2 (Letrozole)

Serious events: 6 serious events

Other events: 57 other events

Deaths: 1 deaths

Ph2P1 (Palbociclib + Letrozole)

Serious events: 10 serious events

Other events: 33 other events

Deaths: 1 deaths

Ph2P1 (Letrozole)

Serious events: 2 serious events

Other events: 22 other events

Deaths: 0 deaths

Ph2P2 (Palbociclib + Letrozole)

Serious events: 12 serious events

Other events: 50 other events

Deaths: 2 deaths

Ph2P2 (Letrozole)

Serious events: 4 serious events

Other events: 35 other events

Deaths: 1 deaths

Serious adverse events

Measure	Phase 1 (Palbociclib + Letrozole) n=12 participants at risk In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Palbociclib + Letrozole) n=83 participants at risk All participants who were randomized to letrozole plus palbociclib in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. In Ph2P1 and Ph2P2, the participants received palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and letrozole 2.5 mg/d orally in a continuous regimen.	Phase 2 (Letrozole) n=77 participants at risk All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) n=33 participants at risk All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) n=29 participants at risk Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) n=50 participants at risk Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) n=48 participants at risk Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Blood and lymphatic system disorders Anaemia	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Cardiac disorders Cardiac failure	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Gastrointestinal disorders Colitis ischaemic	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Gastrointestinal disorders Gastrointestinal disorder	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Gastrointestinal disorders Ileus	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Gastrointestinal disorders Oesophageal achalasia	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
General disorders Asthenia	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
General disorders Chest pain	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
General disorders Disease progression	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
General disorders Pain	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Infections and infestations Erysipelas	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Infections and infestations Gangrene	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Infections and infestations Influenza	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Infections and infestations Pneumonia	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Infections and infestations Staphylococcal bacteraemia	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Fractured sacrum	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Investigations Alanine aminotransferase increased	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Investigations Aspartate aminotransferase increased	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Investigations Blood alkaline phosphatase increased	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Investigations Gamma-glutamyltransferase increased	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.4% 2/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.4% 2/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.0% 2/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Fallopian tube cancer	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Nervous system disorders Neuralgia	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Renal and urinary disorders Nephrolithiasis	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Renal and urinary disorders Renal disorder	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Renal and urinary disorders Urethral obstruction	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.8% 4/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	12.1% 4/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Subcutaneous emphysema	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Gastrointestinal disorders Gastritis	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Gastrointestinal disorders Inguinal hernia	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Infections and infestations Campylobacter infection	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Infections and infestations Infective exacerbation of chronic obstructive airways disease	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Infections and infestations Mastoiditis	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Osteonecrosis of jaw	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasma cell myeloma	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Nervous system disorders Brain stem infarction	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Renal and urinary disorders Acute kidney injury	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.

Other adverse events

Measure	Phase 1 (Palbociclib + Letrozole) n=12 participants at risk In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.	Phase 2 (Palbociclib + Letrozole) n=83 participants at risk All participants who were randomized to letrozole plus palbociclib in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. In Ph2P1 and Ph2P2, the participants received palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and letrozole 2.5 mg/d orally in a continuous regimen.	Phase 2 (Letrozole) n=77 participants at risk All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.	Ph2P1 (Palbociclib + Letrozole) n=33 participants at risk All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P1 (Letrozole) n=29 participants at risk Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.	Ph2P2 (Palbociclib + Letrozole) n=50 participants at risk Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.	Ph2P2 (Letrozole) n=48 participants at risk Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Blood and lymphatic system disorders Leukopenia	66.7% 8/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	43.4% 36/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.9% 3/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	48.5% 16/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	40.0% 20/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.2% 2/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Blood and lymphatic system disorders Lymphopenia	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.6% 3/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Blood and lymphatic system disorders Neutropenia	91.7% 11/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	74.7% 62/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	5.2% 4/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	78.8% 26/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	72.0% 36/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.2% 3/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	25.0% 3/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	19.3% 16/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.6% 2/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	24.2% 8/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	16.0% 8/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Eye disorders Dry eye	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Infections and infestations Conjunctivitis	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.0% 5/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.0% 3/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Eye disorders Lacrimation increased	16.7% 2/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.6% 3/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.0% 2/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Eye disorders Visual impairment	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.8% 4/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.0% 3/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal discomfort	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.6% 2/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.2% 2/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal distension	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.6% 2/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	8.4% 7/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	5.2% 4/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	21.2% 7/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	8.3% 4/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.4% 2/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	5.2% 4/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.2% 3/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Blood and lymphatic system disorders Anaemia	33.3% 4/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	34.9% 29/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.9% 3/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	39.4% 13/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	32.0% 16/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.2% 3/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Gastrointestinal disorders Food poisoning	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Gastrointestinal disorders Chronic gastritis	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Skin disorder	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Infections and infestations Cellulitis	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.4% 2/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.6% 2/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Gastrointestinal disorders Constipation	25.0% 3/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	15.7% 13/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	9.1% 7/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	24.2% 8/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	13.8% 4/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	10.0% 5/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.2% 3/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	50.0% 6/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	21.7% 18/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	11.7% 9/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	27.3% 9/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.9% 2/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	18.0% 9/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	14.6% 7/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Gastrointestinal disorders Dry mouth	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.6% 3/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	5.2% 4/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.9% 2/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.2% 2/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Gastrointestinal disorders Dyspepsia	25.0% 3/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.8% 4/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.6% 2/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.0% 3/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.2% 2/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Gastrointestinal disorders Flatulence	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.4% 2/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Gastrointestinal disorders Gastrooesophageal reflux disease	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Gastrointestinal disorders Gingival pain	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.8% 4/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	8.0% 4/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Gastrointestinal disorders Mouth ulceration	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.4% 2/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	50.0% 6/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	30.1% 25/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	14.3% 11/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	36.4% 12/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	24.1% 7/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	26.0% 13/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	8.3% 4/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Gastrointestinal disorders Stomatitis	16.7% 2/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	12.0% 10/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.6% 2/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	15.2% 5/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	10.0% 5/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Gastrointestinal disorders Rectal haemorrhage	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Gastrointestinal disorders Toothache	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	7.2% 6/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.6% 2/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	10.0% 5/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	25.0% 3/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	18.1% 15/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.9% 3/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	27.3% 9/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.9% 2/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	12.0% 6/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
General disorders Asthenia	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	13.3% 11/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	5.2% 4/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	18.0% 9/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	8.3% 4/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
General disorders Chest pain	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.6% 3/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	5.2% 4/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.9% 2/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.0% 3/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.2% 2/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
General disorders Facial pain	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
General disorders Fatigue	83.3% 10/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	41.0% 34/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	23.4% 18/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	42.4% 14/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	24.1% 7/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	40.0% 20/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	22.9% 11/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
General disorders Influenza like illness	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.0% 5/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.6% 2/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	9.1% 3/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.0% 2/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
General disorders Mucosal inflammation	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	8.4% 7/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.6% 2/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	10.0% 5/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.2% 2/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
General disorders Non-cardiac chest pain	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
General disorders Oedema peripheral	16.7% 2/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	7.2% 6/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	10.4% 8/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	9.1% 3/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	17.2% 5/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.0% 3/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.2% 3/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
General disorders Pain	16.7% 2/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.6% 3/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.9% 3/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.9% 2/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.0% 2/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
General disorders Pyrexia	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	10.8% 9/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.6% 2/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	24.2% 8/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.2% 2/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
General disorders Temperature intolerance	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Immune system disorders Seasonal allergy	16.7% 2/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Infections and infestations Bronchitis	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.6% 3/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.6% 2/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	9.1% 3/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Infections and infestations Cystitis	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.6% 3/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.0% 3/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Infections and infestations Diverticulitis	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.6% 2/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.9% 2/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Infections and infestations Ear infection	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.4% 2/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Infections and infestations Gastroenteritis viral	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Infections and infestations Herpes zoster	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Infections and infestations Influenza	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	9.6% 8/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	12.1% 4/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	8.0% 4/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Infections and infestations Localised infection	16.7% 2/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Infections and infestations Nasopharyngitis	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	14.5% 12/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	9.1% 7/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	21.2% 7/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	10.3% 3/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	10.0% 5/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	8.3% 4/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Infections and infestations Oral herpes	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.6% 3/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	9.1% 3/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Infections and infestations Pneumonia	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.6% 2/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.9% 2/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Infections and infestations Sinusitis	16.7% 2/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.4% 2/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.6% 2/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.9% 2/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Infections and infestations Skin infection	16.7% 2/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.4% 2/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Infections and infestations Tooth infection	16.7% 2/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.4% 2/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	25.0% 3/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	14.5% 12/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.6% 2/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	24.2% 8/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.9% 2/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	8.0% 4/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Infections and infestations Urinary tract infection	16.7% 2/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	10.8% 9/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.5% 5/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	18.2% 6/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	10.3% 3/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.0% 3/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.2% 2/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Infections and infestations Herpes simplex	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Contusion	16.7% 2/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Thermal burn	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Fall	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	8.4% 7/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.9% 3/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	12.1% 4/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.0% 3/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.2% 3/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Investigations Alanine aminotransferase increased	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	7.2% 6/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	9.1% 3/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.0% 3/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Investigations Aspartate aminotransferase increased	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	7.2% 6/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	8.0% 4/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Investigations Blood alkaline phosphatase increased	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	9.6% 8/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.9% 3/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.9% 2/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	12.0% 6/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Investigations Blood creatinine increased	16.7% 2/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.8% 4/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.5% 5/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	10.3% 3/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.0% 3/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.2% 2/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Investigations Blood phosphorus decreased	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.4% 2/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Investigations Gamma-glutamyltransferase increased	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.8% 4/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.0% 2/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Investigations Red blood cell count decreased	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.4% 2/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Investigations Weight decreased	16.7% 2/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.8% 4/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	8.0% 4/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Investigations White blood cell count decreased	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.4% 2/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Metabolism and nutrition disorders Decreased appetite	25.0% 3/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	20.5% 17/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.5% 5/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	27.3% 9/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.9% 2/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	16.0% 8/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.2% 3/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Metabolism and nutrition disorders Diabetes mellitus	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperkalaemia	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.8% 4/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.6% 2/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.0% 2/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypokalaemia	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.4% 2/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyponatraemia	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperuricaemia	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.6% 3/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.6% 2/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.0% 3/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	41.7% 5/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	26.5% 22/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	18.2% 14/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	27.3% 9/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	17.2% 5/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	26.0% 13/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	18.8% 9/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	25.0% 3/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	20.5% 17/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	16.9% 13/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	18.2% 6/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	17.2% 5/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	22.0% 11/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	16.7% 8/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	12.0% 10/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.9% 3/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	18.2% 6/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.9% 2/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	8.0% 4/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Joint swelling	16.7% 2/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.0% 5/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.9% 3/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.9% 2/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	8.0% 4/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	16.7% 2/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.6% 3/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.9% 3/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.9% 2/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.0% 2/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	10.8% 9/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.5% 5/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	9.1% 3/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	10.3% 3/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	12.0% 6/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.2% 2/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Myalgia	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	7.2% 6/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.9% 3/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	8.0% 4/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.2% 3/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Osteonecrosis of jaw	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.6% 3/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.0% 3/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	25.0% 3/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	10.8% 9/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	9.1% 7/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	9.1% 3/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	12.0% 6/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	12.5% 6/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Spinal pain	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.0% 5/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.9% 3/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	8.0% 4/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.2% 3/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Temporomandibular joint syndrome	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Nervous system disorders Dizziness	25.0% 3/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	12.0% 10/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.9% 3/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	9.1% 3/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	10.3% 3/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	14.0% 7/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Nervous system disorders Dysgeusia	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	7.2% 6/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	12.1% 4/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.0% 2/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Nervous system disorders Headache	33.3% 4/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	14.5% 12/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	10.4% 8/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	18.2% 6/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	10.3% 3/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	12.0% 6/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	10.4% 5/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Nervous system disorders Memory impairment	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.4% 2/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Nervous system disorders Neuropathy peripheral	16.7% 2/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	10.8% 9/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	5.2% 4/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	18.2% 6/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.9% 2/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.0% 3/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.2% 2/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Nervous system disorders Paraesthesia	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.6% 2/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.9% 2/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Nervous system disorders Sciatica	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.4% 2/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Nervous system disorders Sinus headache	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Nervous system disorders Syncope	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Psychiatric disorders Anxiety	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.4% 2/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	5.2% 4/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	13.8% 4/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Psychiatric disorders Depression	25.0% 3/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.8% 4/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.5% 5/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	13.8% 4/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.0% 2/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Psychiatric disorders Insomnia	25.0% 3/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	9.6% 8/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	7.8% 6/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	12.1% 4/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	10.3% 3/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	8.0% 4/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.2% 3/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Psychiatric disorders Mood altered	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.8% 4/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.0% 2/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Psychiatric disorders Sleep disorder	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.6% 3/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.0% 3/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Renal and urinary disorders Dysuria	25.0% 3/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.8% 4/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.6% 2/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.9% 2/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.0% 2/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Renal and urinary disorders Pollakiuria	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.8% 4/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	12.1% 4/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Reproductive system and breast disorders Breast discomfort	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.4% 2/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Reproductive system and breast disorders Breast pain	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.4% 2/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	5.2% 4/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	10.3% 3/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Reproductive system and breast disorders Pelvic pain	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.4% 2/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.6% 2/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.2% 2/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Reproductive system and breast disorders Vaginal discharge	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Reproductive system and breast disorders Vulvovaginal pruritus	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	25.0% 3/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	14.5% 12/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	10.4% 8/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	27.3% 9/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	13.8% 4/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.0% 3/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	8.3% 4/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	41.7% 5/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	16.9% 14/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	9.1% 7/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	12.1% 4/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	10.3% 3/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	20.0% 10/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	8.3% 4/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	10.8% 9/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	12.1% 4/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	10.0% 5/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Nasal congestion	16.7% 2/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.4% 2/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	10.8% 9/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	15.2% 5/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	8.0% 4/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Sinus congestion	25.0% 3/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Snoring	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Alopecia	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	21.7% 18/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.6% 2/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	24.2% 8/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	20.0% 10/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Dermatitis contact	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Dry skin	16.7% 2/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	7.2% 6/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	5.2% 4/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	8.0% 4/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.2% 3/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.8% 4/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.0% 3/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Ingrown hair	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Nail disorder	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.0% 5/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	9.1% 3/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.0% 2/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Pain of skin	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.0% 5/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.6% 2/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	8.0% 4/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.2% 2/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Rash	25.0% 3/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	8.4% 7/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	5.2% 4/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	9.1% 3/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	8.0% 4/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.2% 3/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Skin swelling	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Swelling face	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Vascular disorders Haematoma	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.4% 2/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Vascular disorders Hot flush	25.0% 3/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	22.9% 19/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	14.3% 11/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	27.3% 9/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	17.2% 5/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	20.0% 10/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	12.5% 6/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Vascular disorders Hypertension	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	7.2% 6/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.5% 5/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.9% 2/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	10.0% 5/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.2% 3/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Vascular disorders Lymphoedema	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.8% 4/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.0% 2/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Vascular disorders Peripheral vascular disorder	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Vascular disorders Phlebitis	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Ear and labyrinth disorders Vertigo	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.6% 2/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.2% 2/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Endocrine disorders Hyperthyroidism	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Endocrine disorders Thyroid mass	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Eye disorders Cataract	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.4% 2/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Eye disorders Presbyopia	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Gastrointestinal disorders Oral disorder	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
General disorders Chills	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
General disorders Face oedema	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
General disorders Peripheral swelling	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.8% 4/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.6% 2/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.0% 2/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.2% 2/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Infections and infestations Gingivitis	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Infections and infestations Rhinitis	16.7% 2/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Periorbital haemorrhage	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Skin abrasion	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.4% 2/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Skin injury	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Metabolism and nutrition disorders Dehydration	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Arthropathy	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Muscular weakness	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Nervous system disorders Radicular pain	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Renal and urinary disorders Incontinence	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Lower respiratory tract congestion	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Night sweats	8.3% 1/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.6% 3/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.0% 2/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Gastrointestinal disorders Gastritis	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.2% 1/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	5.2% 4/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.9% 2/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.0% 1/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.2% 2/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Investigations Weight increased	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.6% 3/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	7.8% 6/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.0% 1/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.9% 2/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.0% 2/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	8.3% 4/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Ear and labyrinth disorders Ear pain	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.4% 2/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Limb discomfort	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.6% 2/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.9% 2/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Osteoporosis	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.4% 2/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	1.3% 1/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.1% 2/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	2.1% 1/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.6% 3/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.0% 3/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/12 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.6% 3/83 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.9% 3/77 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	0.00% 0/33 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	3.4% 1/29 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	6.0% 3/50 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.	4.2% 2/48 • Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: ClinicalTrials.gov_Inquiries@pfizer.com

Results disclosure agreements

• Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
• Publication restrictions are in place

Restriction type: OTHER