Trial Outcomes & Findings for A Study to Assess the Efficacy of Fluticasone Furoate/Vilanterol (FF/VI) Inhalation Powder 100/25 mcg Once Daily Compared With Fluticasone Propionate/Salmeterol Inhalation Powder 250/50 mcg Twice Daily in Subjects With Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT01706328)

Last Updated: 2018-05-02

Results Overview

FEV1 is a measure of lung function and is defined as the volume of air that can be forcefully exhaled in one second. The weighted mean was calculated from the pre-dose FEV1 and the post-dose FEV1 measurements taken at 5, 15, 30, and 60 minutes and 2, 4, 6, 8, 12, 13, 14, 16, 20, and 24 hours on Treatment Day 84. Baseline trough FEV1 was calculated as the mean of the two assessments made 30 minutes pre-dose and 5 minutes pre-dose on Treatment Day 1. The weighted mean was derived by calculating the area under curve, and then dividing by the relevant time interval. The weighted mean change from Baseline was calculated as the weighted mean of the 24-hour serial FEV1 measurements on Day 84 minus the Baseline trough FEV1 value. The analysis used an analysis of covariance (ANCOVA) model with covariates of Baseline FEV1, reversibility stratum, smoking status (at Screening), country, and treatment.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

828 participants

Primary outcome timeframe

Baseline and Day 84

Results posted on

2018-05-02

Participant Flow

Only those participants that started the Double-blind Treatment Period were considered enrolled.

At Visit 1, participants entered a 2-week, single-blind (placebo) Run-in Period to obtain Baseline assessments of salbutamol use and to evaluate adherence with study treatment and procedures, diary card completion, and assessment of disease stability. At Visit 2, participants were randomized to a 12-week, double-blind Treatment Period.

Participant milestones

Participant milestones
Measure	Placebo + Salbutamol Participants were instructed to take single-blind placebo twice a day (one inhalation from a multi-dose powder inhaler \[MPI\] and one inhalation from a dry powder inhaler \[DPI\] in the morning; one inhalation from an MPI in the evening). In addition, all participants received supplemental albuterol (salbutamol) (via a metered dose inhaler \[MDI\] and/or nebules) to be used on an as-needed basis. Ipratropium bromide alone was permitted, provided that the participant was on a stable dose from Visit 1 (Screening) and remained on the stable dose throughout the study; however, ipratropium must have been withheld for 4 hours prior to and during each clinic visit.	FF/VI 100/25 µg QD Participants received one inhalation of fluticasone furoate/vilanterol (FF/VI) 100/25 micrograms (µg) once daily (QD) in the morning from a DPI and placebo twice daily (BID) from a DPI (one inhalation in the morning and one inhalation in the evening) for 12 weeks. In addition, participants were provided supplemental albuterol (salbutamol) inhalation to be used as needed throughout the study.	FP/Salmeterol 250/50 µg BID Participants received fluticasone propionate (FP)/salmeterol 250/50 µg BID from a DPI (one inhalation in the morning and one inhalation in the evening) plus placebo QD in the morning from a DPI for 12 weeks. In addition, participants were provided supplemental albuterol (salbutamol) to be used as needed throughout the study.
2-week Run-in Period STARTED	993	0	0
2-week Run-in Period COMPLETED	828	0	0
2-week Run-in Period NOT COMPLETED	165	0	0
12-week Double-blind Treatment Period STARTED	0	412	416
12-week Double-blind Treatment Period COMPLETED	0	366	371
12-week Double-blind Treatment Period NOT COMPLETED	0	46	45

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo + Salbutamol Participants were instructed to take single-blind placebo twice a day (one inhalation from a multi-dose powder inhaler \[MPI\] and one inhalation from a dry powder inhaler \[DPI\] in the morning; one inhalation from an MPI in the evening). In addition, all participants received supplemental albuterol (salbutamol) (via a metered dose inhaler \[MDI\] and/or nebules) to be used on an as-needed basis. Ipratropium bromide alone was permitted, provided that the participant was on a stable dose from Visit 1 (Screening) and remained on the stable dose throughout the study; however, ipratropium must have been withheld for 4 hours prior to and during each clinic visit.	FF/VI 100/25 µg QD Participants received one inhalation of fluticasone furoate/vilanterol (FF/VI) 100/25 micrograms (µg) once daily (QD) in the morning from a DPI and placebo twice daily (BID) from a DPI (one inhalation in the morning and one inhalation in the evening) for 12 weeks. In addition, participants were provided supplemental albuterol (salbutamol) inhalation to be used as needed throughout the study.	FP/Salmeterol 250/50 µg BID Participants received fluticasone propionate (FP)/salmeterol 250/50 µg BID from a DPI (one inhalation in the morning and one inhalation in the evening) plus placebo QD in the morning from a DPI for 12 weeks. In addition, participants were provided supplemental albuterol (salbutamol) to be used as needed throughout the study.
2-week Run-in Period Inclusion/Exclusion Criteria Not Met	140	0	0
2-week Run-in Period Withdrawal by Subject	15	0	0
2-week Run-in Period Physician Decision	4	0	0
2-week Run-in Period Adverse Event	4	0	0
2-week Run-in Period Lost to Follow-up	2	0	0
12-week Double-blind Treatment Period Adverse Event	0	14	16
12-week Double-blind Treatment Period Lack of Efficacy	0	4	4
12-week Double-blind Treatment Period Protocol Violation	0	4	2
12-week Double-blind Treatment Period Protocol-defined Stopping Criteria Met	0	11	9
12-week Double-blind Treatment Period Lost to Follow-up	0	3	1
12-week Double-blind Treatment Period Physician Decision	0	2	2
12-week Double-blind Treatment Period Withdrawal by Subject	0	8	11

Baseline Characteristics

A Study to Assess the Efficacy of Fluticasone Furoate/Vilanterol (FF/VI) Inhalation Powder 100/25 mcg Once Daily Compared With Fluticasone Propionate/Salmeterol Inhalation Powder 250/50 mcg Twice Daily in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	FF/VI 100/25 µg QD n=412 Participants Participants received one inhalation of fluticasone furoate/vilanterol (FF/VI) 100/25 micrograms (µg) once daily (QD) in the morning from a DPI and placebo twice daily (BID) from a DPI (one inhalation in the morning and one inhalation in the evening) for 12 weeks. In addition, participants were provided supplemental albuterol (salbutamol) inhalation to be used as needed throughout the study.	FP/Salmeterol 250/50 µg BID n=416 Participants Participants received fluticasone propionate (FP)/salmeterol 250/50 µg BID from a DPI (one inhalation in the morning and one inhalation in the evening) plus placebo QD in the morning from a DPI for 12 weeks. In addition, participants were provided supplemental albuterol (salbutamol) to be used as needed throughout the study.	Total n=828 Participants Total of all reporting groups
Age, Continuous	61.0 Years STANDARD_DEVIATION 8.17 • n=5 Participants	61.3 Years STANDARD_DEVIATION 8.37 • n=7 Participants	61.1 Years STANDARD_DEVIATION 8.27 • n=5 Participants
Sex: Female, Male Female	111 Participants n=5 Participants	122 Participants n=7 Participants	233 Participants n=5 Participants
Sex: Female, Male Male	301 Participants n=5 Participants	294 Participants n=7 Participants	595 Participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage	9 participants n=5 Participants	5 participants n=7 Participants	14 participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized White-White/Caucasian/European Heritage	403 participants n=5 Participants	410 participants n=7 Participants	813 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Day 84

Population: Intent-to-Treat (ITT) Population: all participants who were randomized and received at least one dose of study drug. Only those participants available at the indicated time point were assessed.

Outcome measures

Outcome measures
Measure	FF/VI 100/25 µg QD n=350 Participants Participants received one inhalation of fluticasone furoate/vilanterol (FF/VI) 100/25 micrograms (µg) once daily (QD) in the morning from a DPI and placebo twice daily (BID) from a DPI (one inhalation in the morning and one inhalation in the evening) for 12 weeks. In addition, participants were provided supplemental albuterol (salbutamol) inhalation to be used as needed throughout the study.	FP/Salmeterol 250/50 µg BID n=356 Participants Participants received fluticasone propionate (FP)/salmeterol 250/50 µg BID from a DPI (one inhalation in the morning and one inhalation in the evening) plus placebo QD in the morning from a DPI for 12 weeks. In addition, participants were provided supplemental albuterol (salbutamol) to be used as needed throughout the study.
Change From Baseline Trough in Weighted-mean 24-hour Serial Forced Expiratory Volume in One Second (FEV1) on Treatment Day 84	0.168 Liters Standard Error 0.0121	0.142 Liters Standard Error 0.0120

SECONDARY outcome

Timeframe: Baseline and Day 1

Population: ITT Population. Only those participants available at the indicated time point were assessed.

Time to onset on Treatment Day 1 is defined as the time to an increase of 100 milliliters (mL) from Baseline in FEV1 during the 0- to 4-hour serial measurements (5, 15, 30, 60, 120, and 240 minutes post-dose). Participants who never met or exceeded a 100 mL increase over the Baseline value during the 4-hour serial measurements were censored at the actual time of their last FEV1 measurement.

Outcome measures

Outcome measures
Measure	FF/VI 100/25 µg QD n=411 Participants Participants received one inhalation of fluticasone furoate/vilanterol (FF/VI) 100/25 micrograms (µg) once daily (QD) in the morning from a DPI and placebo twice daily (BID) from a DPI (one inhalation in the morning and one inhalation in the evening) for 12 weeks. In addition, participants were provided supplemental albuterol (salbutamol) inhalation to be used as needed throughout the study.	FP/Salmeterol 250/50 µg BID n=416 Participants Participants received fluticasone propionate (FP)/salmeterol 250/50 µg BID from a DPI (one inhalation in the morning and one inhalation in the evening) plus placebo QD in the morning from a DPI for 12 weeks. In addition, participants were provided supplemental albuterol (salbutamol) to be used as needed throughout the study.
Time to Onset on Treatment Day 1	15 Minutes Interval 5.0 to 240.0	15 Minutes Interval 5.0 to 240.0

SECONDARY outcome

Timeframe: Baseline and Day 85

Population: ITT Population. Only those participants available at the indicated time point were assessed.

FEV1 is a measure of lung function and is defined as the volume of air that can be forcefully exhaled in one second. Trough FEV1 is defined as the 24-hour FEV1 assessment, which was obtained on Day 85. Baseline trough was calculated as the mean of the two assessments made 30 minutes pre-dose and 5 minutes pre-dose on Treatment Day 1. Change from Baseline was calculated as the average of the Day 85 values minus the Baseline value. The analysis used an analysis of covariance (ANCOVA) model with covariates of Baseline FEV1, reversibility stratum, smoking status (at Screening), country, and treatment.

Outcome measures

Outcome measures
Measure	FF/VI 100/25 µg QD n=364 Participants Participants received one inhalation of fluticasone furoate/vilanterol (FF/VI) 100/25 micrograms (µg) once daily (QD) in the morning from a DPI and placebo twice daily (BID) from a DPI (one inhalation in the morning and one inhalation in the evening) for 12 weeks. In addition, participants were provided supplemental albuterol (salbutamol) inhalation to be used as needed throughout the study.	FP/Salmeterol 250/50 µg BID n=369 Participants Participants received fluticasone propionate (FP)/salmeterol 250/50 µg BID from a DPI (one inhalation in the morning and one inhalation in the evening) plus placebo QD in the morning from a DPI for 12 weeks. In addition, participants were provided supplemental albuterol (salbutamol) to be used as needed throughout the study.
Change From Baseline in Trough FEV1 on Treatment Day 85	0.151 Liters Standard Error 0.0126	0.121 Liters Standard Error 0.0125

Adverse Events

FF/VI 100/25 µg QD

Serious events: 13 serious events

Other events: 46 other events

Deaths: 0 deaths

FP/Salmeterol 250/50 µg BID

Serious events: 20 serious events

Other events: 52 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	FF/VI 100/25 µg QD n=412 participants at risk Participants received one inhalation of fluticasone furoate/vilanterol (FF/VI) 100/25 micrograms (µg) once daily (QD) in the morning from a DPI and placebo twice daily (BID) from a DPI (one inhalation in the morning and one inhalation in the evening) for 12 weeks. In addition, participants were provided supplemental albuterol (salbutamol) inhalation to be used as needed throughout the study.	FP/Salmeterol 250/50 µg BID n=416 participants at risk Participants received fluticasone propionate (FP)/salmeterol 250/50 µg BID from a DPI (one inhalation in the morning and one inhalation in the evening) plus placebo QD in the morning from a DPI for 12 weeks. In addition, participants were provided supplemental albuterol (salbutamol) to be used as needed throughout the study.
Infections and infestations Nasopharyngitis	7.3% 30/412 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.	6.2% 26/416 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.
Nervous system disorders Headache	4.4% 18/412 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.	7.0% 29/416 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.

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	FF/VI 100/25 µg QD n=412 participants at risk Participants received one inhalation of fluticasone furoate/vilanterol (FF/VI) 100/25 micrograms (µg) once daily (QD) in the morning from a DPI and placebo twice daily (BID) from a DPI (one inhalation in the morning and one inhalation in the evening) for 12 weeks. In addition, participants were provided supplemental albuterol (salbutamol) inhalation to be used as needed throughout the study.	FP/Salmeterol 250/50 µg BID n=416 participants at risk Participants received fluticasone propionate (FP)/salmeterol 250/50 µg BID from a DPI (one inhalation in the morning and one inhalation in the evening) plus placebo QD in the morning from a DPI for 12 weeks. In addition, participants were provided supplemental albuterol (salbutamol) to be used as needed throughout the study.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.2% 5/412 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.	0.96% 4/416 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/412 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.	0.24% 1/416 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/412 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.	0.24% 1/416 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.
Infections and infestations Pneumonia	0.24% 1/412 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.	0.96% 4/416 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.
Infections and infestations Infective exacerbation of chronic obstructive airways diseas	0.00% 0/412 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.	0.72% 3/416 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.
Infections and infestations Cellulitis	0.00% 0/412 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.	0.24% 1/416 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.
Infections and infestations Clostridium difficile colitis	0.00% 0/412 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.	0.24% 1/416 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.
Cardiac disorders Cardiac failure	0.00% 0/412 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.	0.24% 1/416 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.
Cardiac disorders Cardiac failure chronic	0.00% 0/412 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.	0.24% 1/416 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.
Cardiac disorders Cardiac failure congestive	0.24% 1/412 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.	0.00% 0/416 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.
Cardiac disorders Cor pulmonale	0.00% 0/412 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.	0.24% 1/416 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.
Cardiac disorders Coronary artery disease	0.00% 0/412 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.	0.24% 1/416 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.
Cardiac disorders Myocardial infarction	0.24% 1/412 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.	0.00% 0/416 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.
Injury, poisoning and procedural complications Alcohol poisoning	0.00% 0/412 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.	0.24% 1/416 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/412 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.	0.24% 1/416 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.
Injury, poisoning and procedural complications Fibula fracture	0.24% 1/412 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.	0.00% 0/416 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.
Injury, poisoning and procedural complications Mouth injury	0.24% 1/412 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.	0.00% 0/416 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon neoplasm	0.00% 0/412 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.	0.24% 1/416 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer	0.00% 0/412 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.	0.24% 1/416 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of lung	0.24% 1/412 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.	0.00% 0/416 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.
Nervous system disorders Cerebral infarction	0.24% 1/412 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.	0.00% 0/416 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.
Nervous system disorders Convulsion	0.24% 1/412 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.	0.00% 0/416 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.24% 1/412 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.	0.00% 0/416 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/412 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.	0.24% 1/416 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.
Vascular disorders Hypertensive crisis	0.24% 1/412 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.	0.00% 0/416 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who were randomized and received at least one dose of study drug.