Trial Outcomes & Findings for An Exercise Endurance Study to Evaluate the Effects of Treatment of Chronic Obstructive Pulmonary Disease (COPD) Patients With a Dual Bronchodilator: GSK573719/GW642444. Study A (NCT NCT01328444)

NCT ID: NCT01328444

Last Updated: 2017-10-11

Results Overview

Exercise endurance time (EET) post-dose at Week 12 is defined as the EET obtained 3 hours after dosing at Week 12. EET was measured using the externally paced field walking test called the endurance shuttle walk test (ESWT). Analysis performed using a repeated measures model with covariates of period walking speed, mean walking speed, period, treatment, visit, smoking status, center group, visit by period walking speed, visit by mean walking speed and visit by treatment interactions. The model used all available 3-hour post-dose change from baseline EET values recorded on Day 2, Week 6 and Week 12. Baseline was the EET assessment obtained prior to dosing on Day 1 of each period. The mean walking speed for each participant is the mean of the levels used for the ESWT in each of the two treatment periods. The period walking speed for each participant and treatment period is the difference between the level for that participant and period and the mean walking speed for that participant.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 349 participants
• Primary outcome timeframe: Week 12 of each treatment period (up to Study Week 29)
• Results posted on: 2017-10-11

Participant Flow

Participants (par.) who were eligible completed a 12- to 21-day Run-in Period followed by two 12-week treatment periods.

A total of 596 par. were enrolled and screened, 409 par. entered the Run-in Period, 349 par. were randomized and 348 par. received study treatment. Participant Flow data are presented by treatment rather than sequence. Par. received 2 out of the 6 interventions.

Participant milestones

Measure	Placebo Participants received matching placebo QD via a DPI in the morning for 12 weeks.	UMEC 62.5 µg QD Participants received umeclidinium bromide (UMEC) 62.5 micrograms (µg) QD via a DPI in the morning for 12 weeks.	UMEC 125 µg QD Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks.	VI 25 µg QD Participants received vilanterol (VI) 25 µg QD via a DPI for 12 weeks.	UMEC/VI 62.5/25 µg QD Participants received UMEC/VI 62.5/25 µg QD via a DPI in the morning for 12 weeks.	UMEC 125/25 µg QD Participants received UMEC/VI 125/25 µg QD via a DPI in the morning for 12 weeks.
Treatment Period 1 (12 Weeks) STARTED	94	26	28	41	81	78
Treatment Period 1 (12 Weeks) COMPLETED	83	21	25	33	67	72
Treatment Period 1 (12 Weeks) NOT COMPLETED	11	5	3	8	14	6
Washout Period (14 Days) STARTED	83	21	25	33	67	72
Washout Period (14 Days) COMPLETED	82	20	25	32	66	68
Washout Period (14 Days) NOT COMPLETED	1	1	0	1	1	4
Treatment Period 2 (12 Weeks) STARTED	76	23	22	35	71	66
Treatment Period 2 (12 Weeks) COMPLETED	65	22	19	30	63	59
Treatment Period 2 (12 Weeks) NOT COMPLETED	11	1	3	5	8	7

Reasons for withdrawal

Measure	Placebo Participants received matching placebo QD via a DPI in the morning for 12 weeks.	UMEC 62.5 µg QD Participants received umeclidinium bromide (UMEC) 62.5 micrograms (µg) QD via a DPI in the morning for 12 weeks.	UMEC 125 µg QD Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks.	VI 25 µg QD Participants received vilanterol (VI) 25 µg QD via a DPI for 12 weeks.	UMEC/VI 62.5/25 µg QD Participants received UMEC/VI 62.5/25 µg QD via a DPI in the morning for 12 weeks.	UMEC 125/25 µg QD Participants received UMEC/VI 125/25 µg QD via a DPI in the morning for 12 weeks.
Treatment Period 1 (12 Weeks) Adverse Event	3	1	1	3	5	2
Treatment Period 1 (12 Weeks) Lack of Efficacy	6	1	1	1	6	2
Treatment Period 1 (12 Weeks) Protocol Violation	0	0	0	1	0	1
Treatment Period 1 (12 Weeks) Met Protocol- Defined Stopping Criteria	0	1	0	0	2	0
Treatment Period 1 (12 Weeks) Lost to Follow-up	2	0	0	1	0	1
Treatment Period 1 (12 Weeks) Withdrawal by Subject	0	2	1	2	1	0
Washout Period (14 Days) Adverse Event	1	1	0	1	1	2
Washout Period (14 Days) Lack of Efficacy	0	0	0	0	0	1
Washout Period (14 Days) Withdrawal by Subject	0	0	0	0	0	1
Treatment Period 2 (12 Weeks) Adverse Event	5	0	1	1	1	0
Treatment Period 2 (12 Weeks) Lack of Efficacy	5	1	1	2	3	4
Treatment Period 2 (12 Weeks) Protocol Violation	1	0	0	0	1	0
Treatment Period 2 (12 Weeks) Met Protocol Defined Stopping Criteria	0	0	0	1	1	0
Treatment Period 2 (12 Weeks) Lost to Follow-up	0	0	1	1	1	2
Treatment Period 2 (12 Weeks) Withdrawal by Subject	0	0	0	0	1	1

Baseline Characteristics

An Exercise Endurance Study to Evaluate the Effects of Treatment of Chronic Obstructive Pulmonary Disease (COPD) Patients With a Dual Bronchodilator: GSK573719/GW642444. Study A

Baseline characteristics by cohort

Measure	All Study Treatments n=348 Participants Participants were randomized to receive a sequence consisting of 2 of the following treatments: UMEC/VI 125/25 µg , UMEC/VI 62.5/25 µg , UMEC 125 µg , UMEC 62.5 µg , VI 25 µg , or placebo QD via a DPI. Each treatment was administered in the morning for 12 weeks. The treatment periods were seperated by 14-day washout period.
Age, Continuous	61.6 Years STANDARD_DEVIATION 8.25 • n=5 Participants
Sex: Female, Male Female	153 Participants n=5 Participants
Sex: Female, Male Male	195 Participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage	11 Participants n=5 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	336 Participants n=5 Participants
Race/Ethnicity, Customized Mixed Race	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 12 of each treatment period (up to Study Week 29)

Population: Intent-to-Treat (ITT) Population: all par. randomized to treatment who received at least one dose of study drug in either treatment period. Number of par. represent those with data available at the time point; however, all par. in the ITT population without missing covariate information and with at least one post Baseline measurement are included.

Exercise endurance time (EET) post-dose at Week 12 is defined as the EET obtained 3 hours after dosing at Week 12. EET was measured using the externally paced field walking test called the endurance shuttle walk test (ESWT). Analysis performed using a repeated measures model with covariates of period walking speed, mean walking speed, period, treatment, visit, smoking status, center group, visit by period walking speed, visit by mean walking speed and visit by treatment interactions. The model used all available 3-hour post-dose change from baseline EET values recorded on Day 2, Week 6 and Week 12. Baseline was the EET assessment obtained prior to dosing on Day 1 of each period. The mean walking speed for each participant is the mean of the levels used for the ESWT in each of the two treatment periods. The period walking speed for each participant and treatment period is the difference between the level for that participant and period and the mean walking speed for that participant.

Outcome measures

Measure	Placebo n=145 Participants Participants received matching placebo QD via a DPI in the morning for 12 weeks.	UMEC 62.5 µg QD n=43 Participants Participants received UMEC 62.5 µg QD via a DPI in the morning for 12 weeks.	UMEC 125 µg QD n=44 Participants Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks.	VI 25 µg QD n=63 Participants Participants received vilanterol (VI) 25 µg QD via a DPI for 12 weeks.	UMEC/VI 62.5/25 µg QD n=131 Participants Participants received UMEC/VI 62.5/25 µg QD via a DPI in the morning for 12 weeks.	UMEC/VI 125/25 µg QD n=130 Participants Participants received UMEC/VI 125/25 µg QD via a DPI in the morning for 12 weeks.
Change From Baseline in Exercise Endurance Time Post-dose at Week 12 of Each Treatment Period	36.7 Seconds Standard Error 13.17	63.2 Seconds Standard Error 23.93	49.8 Seconds Standard Error 23.77	26.7 Seconds Standard Error 19.72	58.6 Seconds Standard Error 13.82	69.1 Seconds Standard Error 13.99

PRIMARY outcome

Timeframe: Week 12 of each treatment period (up to Study Week 29)

Population: Intent-to-Treat (ITT) Population: all par. randomized to treatment who received at least one dose of study drug in either treatment period. Number of par. represent those with data available at the time point; however, all par. in the ITT population without missing covariate information and with at least one post Baseline measurement are included.

FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 measurements were taken electronically by spirometry on Day 2, Week 6 and Week 12. Baseline is the FEV1 value recorded pre-dose on Day 1 of each treatment period, mean Baseline is the mean of the Baselines for each participant, and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Clinic visit trough (pre-bronchodilator and pre-dose) FEV1 at Week 12 (Treatment Day 85) is defined as the FEV1 value obtained 24 hours after dosing on Treatment Day 84. Analysis performed using a repeated measures model with covariates of period Baseline, mean Baseline, period, treatment, visit, smoking status, center group, visit by period Baseline, visit by mean Baseline and visit by treatment interactions.

Outcome measures

Measure	Placebo n=148 Participants Participants received matching placebo QD via a DPI in the morning for 12 weeks.	UMEC 62.5 µg QD n=43 Participants Participants received UMEC 62.5 µg QD via a DPI in the morning for 12 weeks.	UMEC 125 µg QD n=44 Participants Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks.	VI 25 µg QD n=64 Participants Participants received vilanterol (VI) 25 µg QD via a DPI for 12 weeks.	UMEC/VI 62.5/25 µg QD n=130 Participants Participants received UMEC/VI 62.5/25 µg QD via a DPI in the morning for 12 weeks.	UMEC/VI 125/25 µg QD n=132 Participants Participants received UMEC/VI 125/25 µg QD via a DPI in the morning for 12 weeks.
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Week 12 of Each Treatment Period	-0.032 Liters Standard Error 0.0149	0.054 Liters Standard Error 0.0264	0.108 Liters Standard Error 0.0263	0.067 Liters Standard Error 0.0218	0.178 Liters Standard Error 0.0156	0.136 Liters Standard Error 0.0158

SECONDARY outcome

Timeframe: Week 12 of each treatment period (up to Study Week 29)

Population: Intent-to-Treat (ITT) population: all par. randomized to treatment who received at least one dose of study drug in either treatment period. Number of par. represent those with data available at the time point; however, all par. in the ITT population without missing covariate information and with at least one post Baseline measurement are included.

Inspiratory capacity (IC) is defined as the maximum amount of air that can be inhaled into the lungs from the normal resting position after breathing out normally. Baseline is the IC value recorded pre-dose on Day 1 of each treatment period, mean Baseline is the mean of the Baselines for each participant, and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Trough IC is measured pre-dose on Treatment Week 12 of each treatment period. IC 3-hours post-dose is measured from the value obtained 3 hours after dosing on Treatment Week 12 of each treatment period. Analysis performed using a repeated measures model with covariates of period Baseline, mean Baseline, period, treatment, visit, smoking status, center group, visit by period Baseline, visit by mean Baseline and visit by treatment interactions. IC measurements were taken electronically by plethysmography on Day 2, Week 6 and Week 12.

Outcome measures

Measure	Placebo n=148 Participants Participants received matching placebo QD via a DPI in the morning for 12 weeks.	UMEC 62.5 µg QD n=43 Participants Participants received UMEC 62.5 µg QD via a DPI in the morning for 12 weeks.	UMEC 125 µg QD n=44 Participants Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks.	VI 25 µg QD n=64 Participants Participants received vilanterol (VI) 25 µg QD via a DPI for 12 weeks.	UMEC/VI 62.5/25 µg QD n=131 Participants Participants received UMEC/VI 62.5/25 µg QD via a DPI in the morning for 12 weeks.	UMEC/VI 125/25 µg QD n=132 Participants Participants received UMEC/VI 125/25 µg QD via a DPI in the morning for 12 weeks.
Change From Baseline in Inspiratory Capacity (Trough and 3-hours Post-dose) at Week 12 of Each Treatment Period Trough	-0.002 Liters Standard Error 0.0255	0.025 Liters Standard Error 0.0457	0.187 Liters Standard Error 0.0457	0.067 Liters Standard Error 0.0377	0.196 Liters Standard Error 0.0269	0.168 Liters Standard Error 0.0270
Change From Baseline in Inspiratory Capacity (Trough and 3-hours Post-dose) at Week 12 of Each Treatment Period 3-hours post-dose	0.028 Liters Standard Error 0.0259	0.142 Liters Standard Error 0.0463	0.249 Liters Standard Error 0.0462	0.160 Liters Standard Error 0.0382	0.267 Liters Standard Error 0.0274	0.250 Liters Standard Error 0.0275

SECONDARY outcome

Timeframe: Week 12 of each treatment period (up to Study Week 29)

Population: Intent-to-Treat (ITT) population: all par. randomized to treatment who received at least one dose of study drug in either treatment period. Number of par. represent those with data available at the time point; however, all par. in the ITT population without missing covariate information and with at least one post Baseline measurement are included.

Functional Residual Capacity (FRC) is defined as the amount of air still left in the lungs after breathing out normally. Baseline is the FRC value recorded pre-dose on Day 1 of each treatment period, mean Baseline is the mean of the Baselines for each participant, and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Trough FRC is measured pre-dose on Treatment Week 12. FRC 3-hours post-dose is measured from the value obtained 3 hours after dosing on Treatment Week 12. Analysis performed using a repeated measures model with covariates of period Baseline, mean Baseline, period, treatment, visit, smoking status, center group, visit by period Baseline, visit by mean Baseline and visit by treatment interactions. FRC measurements were taken electronically by plethysmography on Day 2, Week 6 and Week 12.

Outcome measures

Measure	Placebo n=148 Participants Participants received matching placebo QD via a DPI in the morning for 12 weeks.	UMEC 62.5 µg QD n=43 Participants Participants received UMEC 62.5 µg QD via a DPI in the morning for 12 weeks.	UMEC 125 µg QD n=44 Participants Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks.	VI 25 µg QD n=64 Participants Participants received vilanterol (VI) 25 µg QD via a DPI for 12 weeks.	UMEC/VI 62.5/25 µg QD n=131 Participants Participants received UMEC/VI 62.5/25 µg QD via a DPI in the morning for 12 weeks.	UMEC/VI 125/25 µg QD n=132 Participants Participants received UMEC/VI 125/25 µg QD via a DPI in the morning for 12 weeks.
Change From Baseline in Functional Residual Capacity (Trough and 3-hours Post-dose) at Week 12 of Each Treatment Period 3-hours post-dose	-0.081 Liters Standard Error 0.0495	-0.358 Liters Standard Error 0.0893	-0.456 Liters Standard Error 0.0885	-0.229 Liters Standard Error 0.0734	-0.384 Liters Standard Error 0.0523	-0.548 Liters Standard Error 0.0526
Change From Baseline in Functional Residual Capacity (Trough and 3-hours Post-dose) at Week 12 of Each Treatment Period Trough	0.020 Liters Standard Error 0.0494	-0.262 Liters Standard Error 0.0899	-0.241 Liters Standard Error 0.0890	-0.109 Liters Standard Error 0.0738	-0.219 Liters Standard Error 0.0523	-0.350 Liters Standard Error 0.0524

SECONDARY outcome

Timeframe: Week 12 of each treatment period (up to Study Week 29)

Population: Intent-to-Treat (ITT) population: all par. randomized to treatment who received at least one dose of study drug in either treatment period. Number of par. represent those with data available at the time point; however, all par. in the ITT population without missing covariate information and with at least one post Baseline measurement are included.

Residual Volume (RV) is defined as the air that remains in the lungs after breathing out as fully as possible. Baseline is the RV value recorded pre-dose on Day 1 of each treatment period, mean Baseline is the mean of the Baselines for each participant, and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Trough RV is measured pre-dose on Treatment Week 12. RV 3-hours post-dose is measured from the value obtained 3 hours after dosing on Treatment Week 12. Analysis performed using a repeated measures model with covariates of period Baseline, mean Baseline, period, treatment, visit, smoking status, center group, visit by period Baseline, visit by mean Baseline and visit by treatment interactions. RV measurements were taken electronically by plethysmography on Day 2, Week 6 and Week 12.

Outcome measures

Measure	Placebo n=148 Participants Participants received matching placebo QD via a DPI in the morning for 12 weeks.	UMEC 62.5 µg QD n=43 Participants Participants received UMEC 62.5 µg QD via a DPI in the morning for 12 weeks.	UMEC 125 µg QD n=44 Participants Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks.	VI 25 µg QD n=64 Participants Participants received vilanterol (VI) 25 µg QD via a DPI for 12 weeks.	UMEC/VI 62.5/25 µg QD n=131 Participants Participants received UMEC/VI 62.5/25 µg QD via a DPI in the morning for 12 weeks.	UMEC/VI 125/25 µg QD n=132 Participants Participants received UMEC/VI 125/25 µg QD via a DPI in the morning for 12 weeks.
Change From Baseline in Residual Volume (Trough and 3-hours Post-dose) at Week 12 of Each Treatment Period Trough	0.039 Liters Standard Error 0.0521	-0.337 Liters Standard Error 0.0948	-0.249 Liters Standard Error 0.0940	-0.138 Liters Standard Error 0.0779	-0.255 Liters Standard Error 0.0552	-0.432 Liters Standard Error 0.0553
Change From Baseline in Residual Volume (Trough and 3-hours Post-dose) at Week 12 of Each Treatment Period 3-hours post-dose	-0.086 Liters Standard Error 0.0526	-0.375 Liters Standard Error 0.0955	-0.451 Liters Standard Error 0.0945	-0.253 Liters Standard Error 0.0784	-0.437 Liters Standard Error 0.0556	-0.625 Liters Standard Error 0.0560

SECONDARY outcome

Timeframe: Week 12 of each treatment period (up to Study Week 29)

Population: Intent-to-Treat (ITT) population: all par. randomized to treatment who received at least one dose of study drug in either treatment period. Number of par. represent those with data available at the time point; however, all par. in the ITT population without missing covariate information and with at least one post Baseline measurement are included.

FEVI is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Baseline is the FEV1 value recorded pre-dose on Day 1 of each treatment period, mean Baseline is the mean of the Baselines for each participant, and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Clinic visit post-dose FEV1 at Week 12 (Treatment Day 85) is defined as the FEV1 value obtained 3 hours after dosing on Treatment Day 85. Analysis performed using a repeated measures model with covariates of period Baseline, mean Baseline, period, treatment, visit, smoking status, center group, visit by period Baseline, visit by mean Baseline and visit by treatment interactions 3 hour post-dose FEV1 measurements were taken electronically by spirometry on Day 2, Week 6 and Week 12.

Outcome measures

Measure	Placebo n=147 Participants Participants received matching placebo QD via a DPI in the morning for 12 weeks.	UMEC 62.5 µg QD n=43 Participants Participants received UMEC 62.5 µg QD via a DPI in the morning for 12 weeks.	UMEC 125 µg QD n=44 Participants Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks.	VI 25 µg QD n=64 Participants Participants received vilanterol (VI) 25 µg QD via a DPI for 12 weeks.	UMEC/VI 62.5/25 µg QD n=130 Participants Participants received UMEC/VI 62.5/25 µg QD via a DPI in the morning for 12 weeks.	UMEC/VI 125/25 µg QD n=130 Participants Participants received UMEC/VI 125/25 µg QD via a DPI in the morning for 12 weeks.
Change From Baseline in 3-hours Post-dose FEV1 at Week 12 of Each Treatment Period	-0.007 Liters Standard Error 0.0159	0.122 Liters Standard Error 0.0277	0.156 Liters Standard Error 0.0275	0.115 Liters Standard Error 0.0229	0.254 Liters Standard Error 0.0166	0.217 Liters Standard Error 0.0169

Adverse Events

Placebo

Serious events: 6 serious events

Other events: 18 other events

Deaths: 0 deaths

UMEC 62.5 µg QD

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

UMEC 125 µg QD

Serious events: 3 serious events

Other events: 5 other events

Deaths: 0 deaths

VI 25 µg QD

Serious events: 7 serious events

Other events: 7 other events

Deaths: 0 deaths

UMEC/VI 62.5/25 µg QD

Serious events: 4 serious events

Other events: 8 other events

Deaths: 0 deaths

UMEC/VI 125/25 µg QD

Serious events: 4 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=170 participants at risk Participants received matching placebo QD via a DPI in the morning for 12 weeks.	UMEC 62.5 µg QD n=49 participants at risk Participants received UMEC 62.5 µg QD via a DPI in the morning for 12 weeks.	UMEC 125 µg QD n=50 participants at risk Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks.	VI 25 µg QD n=76 participants at risk Participants received vilanterol (VI) 25 µg QD via a DPI for 12 weeks.	UMEC/VI 62.5/25 µg QD n=152 participants at risk Participants received UMEC/VI 62.5/25 µg QD via a DPI in the morning for 12 weeks.	UMEC/VI 125/25 µg QD n=144 participants at risk Participants received UMEC/VI 125/25 µg QD via a DPI in the morning for 12 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.00% 0/170 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/49 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/50 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/76 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.66% 1/152 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/144 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/170 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/49 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/50 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/76 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.66% 1/152 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/144 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/170 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/49 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	2.0% 1/50 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/76 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/152 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/144 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oropharyngeal cancer stage III	0.00% 0/170 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/49 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/50 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/76 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/152 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.69% 1/144 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.00% 0/170 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/49 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/50 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	1.3% 1/76 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/152 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/144 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Infections and infestations Pneumonia	0.00% 0/170 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/49 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/50 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	1.3% 1/76 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/152 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.69% 1/144 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Infections and infestations Bronchitis	0.59% 1/170 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/49 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/50 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/76 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/152 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/144 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Infections and infestations Perirectal abscess	0.59% 1/170 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/49 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/50 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/76 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/152 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/144 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Cardiac disorders Angina pectoris	0.59% 1/170 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/49 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/50 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/76 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/152 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/144 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Cardiac disorders Bundle branch block left	0.00% 0/170 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/49 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/50 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	1.3% 1/76 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/152 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/144 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Cardiac disorders Myocardial infarction	0.00% 0/170 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/49 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/50 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/76 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.66% 1/152 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/144 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
General disorders Non-cardiac chest pain	0.59% 1/170 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/49 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/50 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	1.3% 1/76 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/152 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/144 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
General disorders Death	0.00% 0/170 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/49 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	2.0% 1/50 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/76 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/152 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/144 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.59% 1/170 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/49 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/50 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/76 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/152 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.69% 1/144 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/170 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/49 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/50 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	1.3% 1/76 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/152 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/144 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/170 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/49 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/50 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	1.3% 1/76 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/152 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/144 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/170 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/49 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/50 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/76 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.66% 1/152 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/144 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Nervous system disorders Carotid artery stenosis	0.59% 1/170 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/49 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/50 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/76 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/152 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/144 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Nervous system disorders Cerebrovascular accident	0.59% 1/170 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/49 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/50 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/76 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/152 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/144 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Eye disorders Cataract	0.00% 0/170 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/49 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/50 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	1.3% 1/76 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/152 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/144 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Gastrointestinal disorders Abdominal pain	0.00% 0/170 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/49 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/50 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/76 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/152 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.69% 1/144 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.00% 0/170 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/49 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	2.0% 1/50 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/76 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/152 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/144 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Renal and urinary disorders Renal failure	0.59% 1/170 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/49 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/50 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/76 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/152 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/144 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Vascular disorders Hypertension	0.59% 1/170 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/49 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/50 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/76 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/152 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/144 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.

Other adverse events

Measure	Placebo n=170 participants at risk Participants received matching placebo QD via a DPI in the morning for 12 weeks.	UMEC 62.5 µg QD n=49 participants at risk Participants received UMEC 62.5 µg QD via a DPI in the morning for 12 weeks.	UMEC 125 µg QD n=50 participants at risk Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks.	VI 25 µg QD n=76 participants at risk Participants received vilanterol (VI) 25 µg QD via a DPI for 12 weeks.	UMEC/VI 62.5/25 µg QD n=152 participants at risk Participants received UMEC/VI 62.5/25 µg QD via a DPI in the morning for 12 weeks.	UMEC/VI 125/25 µg QD n=144 participants at risk Participants received UMEC/VI 125/25 µg QD via a DPI in the morning for 12 weeks.
Infections and infestations Nasopharyngitis	5.9% 10/170 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	2.0% 1/49 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	2.0% 1/50 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	3.9% 3/76 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	3.3% 5/152 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	5.6% 8/144 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Infections and infestations Sinusitis	1.8% 3/170 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/49 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	4.0% 2/50 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/76 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/152 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	2.8% 4/144 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Nervous system disorders Headache	4.1% 7/170 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/49 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	2.0% 1/50 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	5.3% 4/76 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	2.0% 3/152 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	1.4% 2/144 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.
Gastrointestinal disorders Dry mouth	0.00% 0/170 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/49 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	4.0% 2/50 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/76 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/152 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.	0.00% 0/144 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported. SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.

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