Trial Outcomes & Findings for A Phase IIIb Study to Evaluate the Efficacy of Umeclidinium/Vilanterol (UMEC/VI) in Subjects With Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT02152605)

Last Updated: 2017-11-09

Results Overview

The SGRQ is a disease-specific questionnaire, self-completed by participants(par), used to evaluate the effect of UMEC/VI on health-related quality of life as compared to placebo in par with COPD. The scores range from 0 (minimum, best possible health status) to 100 (maximum, worst possible health status). The SGRQ contains 76 items grouped into three domains (symptoms, activity and impacts). Analysis was performed using mixed model repeated measures with covariates of Baseline (scores recorded prior to dosing on Day 1) SGRQ total score, centre group, smoking status, Day, treatment(trt), Day by Baseline interaction and Day by trt interaction, where Day is nominal. Change from Baseline at a particular visit was calculated as the SGRQ total score at that visit minus Baseline. Change from Baseline in total score of -4 units or lower is considered as clinically meaningful improvement in quality of life.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

498 participants

Primary outcome timeframe

Baseline and Day 84

Results posted on

2017-11-09

Participant Flow

In this randomized, double-blind, placebo-controlled parallel study, eligible participants received Umeclidinium/Vilanterol(UMEC/VI) 62.5/25 microgram(mcg) once daily(via Dry Powder Inhaler\[DPI\]) or matching placebo(1:1) for 12 weeks.The study consisted of Run-in Period(7-14 days), treatment period(12 weeks) and follow up period(7+-2 days).

A total of 627 participants who met eligibility criteria were screened; 498 participants were randomized and 496 comprised the Intent to Treat population.

Participant milestones

Participant milestones
Measure	Placebo Participants with chronic obstructive pulmonary disease (COPD) received matching placebo via DPI once daily for 12 weeks. In addition, albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the run-in and double-blind treatment periods. Participants were followed up 7 days after the last dose of study medication.	UMEC/VI 62.5/25 mcg Participants with COPD received UMEC/VI 62.5/25mcg via DPI once daily for 12 weeks. In addition, albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the run-in and double-blind treatment periods. Participants were followed up 7 days after the last dose of study medication.
Overall Study STARTED	248	248
Overall Study COMPLETED	229	230
Overall Study NOT COMPLETED	19	18

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants with chronic obstructive pulmonary disease (COPD) received matching placebo via DPI once daily for 12 weeks. In addition, albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the run-in and double-blind treatment periods. Participants were followed up 7 days after the last dose of study medication.	UMEC/VI 62.5/25 mcg Participants with COPD received UMEC/VI 62.5/25mcg via DPI once daily for 12 weeks. In addition, albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the run-in and double-blind treatment periods. Participants were followed up 7 days after the last dose of study medication.
Overall Study Adverse Event	6	8
Overall Study Lack of Efficacy	7	4
Overall Study Protocol deviation	1	4
Overall Study Lost to Follow-up	1	0
Overall Study Withdrew consent	4	2

Baseline Characteristics

A Phase IIIb Study to Evaluate the Efficacy of Umeclidinium/Vilanterol (UMEC/VI) in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=248 Participants Participants with chronic obstructive pulmonary disease (COPD) received matching placebo via DPI once daily for 12 weeks. In addition, albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the run-in and double-blind treatment periods. Participants were followed up 7 days after the last dose of study medication.	UMEC/VI 62.5/25 mcg n=248 Participants Participants with COPD received UMEC/VI 62.5/25mcg via DPI once daily for 12 weeks. In addition, albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the run-in and double-blind treatment periods. Participants were followed up 7 days after the last dose of study medication.	Total n=496 Participants Total of all reporting groups
Age, Continuous	62.6 Years STANDARD_DEVIATION 8.23 • n=5 Participants	64.1 Years STANDARD_DEVIATION 8.70 • n=7 Participants	63.4 Years STANDARD_DEVIATION 8.49 • n=5 Participants
Sex: Female, Male Female	99 Participants n=5 Participants	104 Participants n=7 Participants	203 Participants n=5 Participants
Sex: Female, Male Male	149 Participants n=5 Participants	144 Participants n=7 Participants	293 Participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized White - White/Caucasian/European	245 Participants n=5 Participants	244 Participants n=7 Participants	489 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Day 84

Population: Intent-to-Treat (ITT) Population: all par. randomized to trt. who received at least one dose of randomized study drug. Par. represents those with data available at the time point being presented; however, all par. in the ITT population without missing covariate information and with at least one post BL measurement are included in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=210 Participants Participants with chronic obstructive pulmonary disease (COPD) received matching placebo via DPI once daily for 12 weeks. In addition, albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the run-in and double-blind treatment periods. Participants were followed up 7 days after the last dose of study medication.	UMEC/VI 62.5/25 mcg n=212 Participants Participants with COPD received UMEC/VI 62.5/25mcg via DPI once daily for 12 weeks. In addition, albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the run-in and double-blind treatment periods. Participants were followed up 7 days after the last dose of study medication.
Change From Baseline in Mean St.George's Respiratory Questionnaire (SGRQ) Total Score at Day 84	-2.12 Score on scale Standard Error 0.808	-6.15 Score on scale Standard Error 0.803

SECONDARY outcome

Timeframe: Baseline and Day 84

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 Days 28, 56 and 84. Baseline is defined as the assessment taken pre-dose on Treatment Day 1. Trough FEV1 is defined as the FEV1 value obtained 24 hours after the previous morning's dosing. Change from Baseline at a particular visit was calculated as the trough FEV1 at that visit minus Baseline. Analysis was performed using a repeated measures model with covariates of treatment, Baseline , smoking status, center group, day, and day by Baseline and day by treatment interactions.

Outcome measures

Outcome measures
Measure	Placebo n=224 Participants Participants with chronic obstructive pulmonary disease (COPD) received matching placebo via DPI once daily for 12 weeks. In addition, albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the run-in and double-blind treatment periods. Participants were followed up 7 days after the last dose of study medication.	UMEC/VI 62.5/25 mcg n=227 Participants Participants with COPD received UMEC/VI 62.5/25mcg via DPI once daily for 12 weeks. In addition, albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the run-in and double-blind treatment periods. Participants were followed up 7 days after the last dose of study medication.
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 84	0.030 Liter Standard Error 0.0183	0.152 Liter Standard Error 0.0181

SECONDARY outcome

Timeframe: Week 1 amd Week 12

Population: Intent-to-Treat (ITT) Population: all par. randomized to trt. who received at least one dose of randomized study drug. Par. represents all par. in the ITT population without missing covariate information and with at least one post BL measurement.

Albuterol/salbutamol(A/S) was used as rescue medication and was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout treatment periods. The number of puffs of rescue medication (A/S) per day over the entire 12 week treatment period was recorded and analyzed. For rescue use, 'day' is referred as the period between one record of rescue use and the next. Total puffs of rescue for each day = number of salbutamol puffs + (2 x number of salbutamol nebules). Analysis performed using mixed model repeated measures with covariates of BL(mean number of total puffs over the duration from First Day; defined as Latest of \[7 days before Visit 2 and day after Visit 1\] to Last Day(defined as Day before Visit 2)), smoking status, centre group, four-week period, treatment and period by BL interaction. Change from BL used weeks 1-4, 5-8, and 9-12 as covariates in the model and the overall least squares mean change for weeks 1-12 is estimated.

Outcome measures

Outcome measures
Measure	Placebo n=247 Participants Participants with chronic obstructive pulmonary disease (COPD) received matching placebo via DPI once daily for 12 weeks. In addition, albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the run-in and double-blind treatment periods. Participants were followed up 7 days after the last dose of study medication.	UMEC/VI 62.5/25 mcg n=244 Participants Participants with COPD received UMEC/VI 62.5/25mcg via DPI once daily for 12 weeks. In addition, albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the run-in and double-blind treatment periods. Participants were followed up 7 days after the last dose of study medication.
Change From Baseline (BL) in Mean Number of Puffs of Rescue Medication Per Day Used Over Weeks 1-12	-0.6 puffs per day Standard Error 0.13	-1.4 puffs per day Standard Error 0.13

Adverse Events

Placebo

Serious events: 13 serious events

Other events: 30 other events

Deaths: 0 deaths

UMEC/VI 62.5/25mcg

Serious events: 17 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=248 participants at risk Participants with chronic obstructive pulmonary disease (COPD) received matching placebo via DPI once daily for 12 weeks. In addition, albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the run-in and double-blind treatment periods. Participants were followed up 7 days after the last dose of study medication.	UMEC/VI 62.5/25mcg n=248 participants at risk Participants with COPD received UMEC/VI 62.5/25mcg via DPI once daily for 12 weeks. In addition, albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the run-in and double-blind treatment periods. Participants were followed up 7 days after the last dose of study medication.
Nervous system disorders Headache	6.5% 16/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	6.5% 16/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
Infections and infestations Nasopharyngitis	6.5% 16/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	5.2% 13/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=248 participants at risk Participants with chronic obstructive pulmonary disease (COPD) received matching placebo via DPI once daily for 12 weeks. In addition, albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the run-in and double-blind treatment periods. Participants were followed up 7 days after the last dose of study medication.	UMEC/VI 62.5/25mcg n=248 participants at risk Participants with COPD received UMEC/VI 62.5/25mcg via DPI once daily for 12 weeks. In addition, albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the run-in and double-blind treatment periods. Participants were followed up 7 days after the last dose of study medication.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	2.8% 7/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	3.2% 8/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
Infections and infestations Pneumonia bacterial	0.40% 1/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	0.00% 0/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
Infections and infestations Appendicitis	0.00% 0/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	0.40% 1/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
Infections and infestations Pneumonia	0.81% 2/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	1.2% 3/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
Cardiac disorders Myocardial ischaemia	0.00% 0/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	0.40% 1/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
Cardiac disorders Cardiac arrest	0.00% 0/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	0.40% 1/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
Cardiac disorders Atrial fibrillation	0.00% 0/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	0.40% 1/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
Cardiac disorders Myocardial infarction	0.40% 1/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	0.40% 1/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
Cardiac disorders Acute myocardial infarction	0.40% 1/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	0.40% 1/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
Injury, poisoning and procedural complications Joint injury	0.00% 0/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	0.40% 1/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
Injury, poisoning and procedural complications Fall	0.00% 0/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	0.40% 1/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
Musculoskeletal and connective tissue disorders Psoriatic arthropathy	0.00% 0/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	0.40% 1/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
Musculoskeletal and connective tissue disorders Arthralgia	0.40% 1/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	0.00% 0/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
Metabolism and nutrition disorders Dyslipidaemia	0.00% 0/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	0.40% 1/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Mediastinum neoplasm	0.00% 0/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	0.40% 1/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
Nervous system disorders Transient ischaemic attack	0.00% 0/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	0.40% 1/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.	0.40% 1/248 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]). SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.