Trial Outcomes & Findings for Study to Compare the Addition of Umeclidinium Bromide (UMEC) to Fluticasone Furoate (FF)/Vilanterol (VI), With Placebo Plus FF/VI in Subjects With Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT01957163)

NCT ID: NCT01957163

Last Updated: 2017-11-09

Results Overview

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 on Day 85 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on Day 84. Analysis was performed using a mixed model repeated measures (MMRM) with covariates of treatment, Baseline FEV1, smoking status, Day, treatment, Day by baseline interaction and Day by treatment interaction, Day being nominal. Baseline FEV1 is the mean of the two assessments made at 30 and 5 minutes (min) pre-dose on Day 1. The change from baseline value is the difference between the on-treatment value and the baseline value.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

619 participants

Primary outcome timeframe

Day 85

Results posted on

2017-11-09

Participant Flow

Participants ≥ 40 years of age with history of chronic obstructive pulmonary disease (COPD) and a smoking history of ≥ 10 pack-years were enrolled in the study. Participants completed a 4-week run-in period, in which they received fluticasone furoate 100 micrograms(µg)/vilanterol 25 µg, followed by a 12-week treatment period and 1-week follow-up.

A total of 619 participants (pars.), representing the enrolled particpants, were randomized to study treatment and comprised the Intent-to-Treat (ITT) Population (participants randomized to treatment who received ≥ 1 dose of randomized study medication in the treatment period).

Participant milestones

Participant milestones
Measure	FF/VI 100/25 µg + Placebo Participants received one inhalation of fluticasone furoate/vilanterol (FF/VI) 100/25 µg once-daily (OD) via a dry powder inhaler (DPI), followed by one inhalation of umeclidinium bromide (UMEC) matching placebo, administered via a dry powder inahler in the morning for 12weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms.	FF/VI 100/25 µg + UMEC 62.5 µg Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg once- daily via a dry powder inhalerfollowed by one inhalation of umeclidinium bromide 62.5 µg administered via a dry powder inhaler in the morning for 12weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms.	FF/VI 100/25 µg + UMEC 125 µg Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg once- daily via a dry powder inhaler followed by one inhalation of umeclidinium bromide 125 µg administered via a dry powder inhaler in the morning for 12 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms.
Overall Study STARTED	206	206	207
Overall Study COMPLETED	191	195	189
Overall Study NOT COMPLETED	15	11	18

Reasons for withdrawal

Reasons for withdrawal
Measure	FF/VI 100/25 µg + Placebo Participants received one inhalation of fluticasone furoate/vilanterol (FF/VI) 100/25 µg once-daily (OD) via a dry powder inhaler (DPI), followed by one inhalation of umeclidinium bromide (UMEC) matching placebo, administered via a dry powder inahler in the morning for 12weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms.	FF/VI 100/25 µg + UMEC 62.5 µg Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg once- daily via a dry powder inhalerfollowed by one inhalation of umeclidinium bromide 62.5 µg administered via a dry powder inhaler in the morning for 12weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms.	FF/VI 100/25 µg + UMEC 125 µg Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg once- daily via a dry powder inhaler followed by one inhalation of umeclidinium bromide 125 µg administered via a dry powder inhaler in the morning for 12 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms.
Overall Study Adverse Event	5	2	4
Overall Study Lack of Efficacy	5	4	9
Overall Study Protocol Violation	1	2	0
Overall Study Met Protocol-Defined Stopping Criteria	0	0	1
Overall Study Lost to Follow-up	0	1	0
Overall Study Withdrawal by Subject	4	2	4

Baseline Characteristics

Study to Compare the Addition of Umeclidinium Bromide (UMEC) to Fluticasone Furoate (FF)/Vilanterol (VI), With Placebo Plus FF/VI in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	FF/VI 100/25 µg + Placebo n=206 Participants Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg OD via a DPI, followed by one inhalation of UMEC matching placebo, administered via a DPI in the morning for 12weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms.	FF/VI 100/25 µg + UMEC 62.5 µg n=206 Participants Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg OD via a DPI followed by one inhalation of UMEC 62.5 µg administered via a DPI in the morning for 12weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms.	FF/VI 100/25 µg + UMEC 125 µg n=207 Participants Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg OD via a DPI followed by one inhalation of UMEC 125 µg administered via a DPI in the morning for 12 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms.	Total n=619 Participants Total of all reporting groups
Age, Continuous	64.7 Years STANDARD_DEVIATION 7.90 • n=5 Participants	64.9 Years STANDARD_DEVIATION 8.72 • n=7 Participants	63.8 Years STANDARD_DEVIATION 7.65 • n=5 Participants	64.4 Years STANDARD_DEVIATION 8.10 • n=4 Participants
Sex: Female, Male Female	65 Participants n=5 Participants	67 Participants n=7 Participants	80 Participants n=5 Participants	212 Participants n=4 Participants
Sex: Female, Male Male	141 Participants n=5 Participants	139 Participants n=7 Participants	127 Participants n=5 Participants	407 Participants n=4 Participants
Race/Ethnicity, Customized African American/African Heritage	5 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	14 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	200 Participants n=5 Participants	201 Participants n=7 Participants	202 Participants n=5 Participants	603 Participants n=4 Participants

PRIMARY outcome

Timeframe: Day 85

Population: ITT Population: all pars. randomized to treatment who received ≥ 1 dose of randomized study medication in the Treatment Period. Number of pars. presented represent those with data available at given time point; however, all pars. in the ITT population without missing covariate information, with ≥ 1 post BL measurement are included in the analysis.

Outcome measures

Outcome measures
Measure	FF/VI 100/25 µg + Placebo n=190 Participants Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg OD via a DPI, followed by one inhalation of UMEC matching placebo, administered via a DPI in the morning for 12weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms.	FF/VI 100/25 µg + UMEC 62.5 µg n=195 Participants Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg OD via a DPI followed by one inhalation of UMEC 62.5 µg administered via a DPI in the morning for 12weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms.	FF/VI 100/25 µg + UMEC 125 µg n=188 Participants Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg OD via a DPI followed by one inhalation of UMEC 125 µg administered via a DPI in the morning for 12 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms.
Change From Baseline (BL) in Trough Forced Expiratory Volume in One Second (FEV1) at Day 85	-0.020 Liters Standard Error 0.0111	0.103 Liters Standard Error 0.0110	0.108 Liters Standard Error 0.0111

SECONDARY outcome

Timeframe: Day 84

Population: ITT Population. Number of participants presented represent those with data available at the time point being presented; however, all participants in the ITT population without missing covariate information and with at least one post baseline measurement are included in the analysis.

FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. The 0-6 hour weighted mean was derived by calculating the area under the FEV1/time curve over the nominal time points of 0 hour (trough value), 15 and 30 min, 1, 3 and 6 hours, using the trapezoidal rule, and then dividing by the actual time between dosing and the 6 hour assessment. Analysis was performed using MMRM with covariates of treatment, Baseline FEV1 (mean of the two assessments made 30 minutes and 5 minutes pre-dose on Day 1), smoking status, Day, and Day by Baseline and Day by treatment interactions. Baseline FEV1 is the mean of the two assessments made at 30 and 5 min pre-dose on Day 1. The change from baseline value is the difference between the on-treatment value and the baseline value.

Outcome measures

Outcome measures
Measure	FF/VI 100/25 µg + Placebo n=191 Participants Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg OD via a DPI, followed by one inhalation of UMEC matching placebo, administered via a DPI in the morning for 12weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms.	FF/VI 100/25 µg + UMEC 62.5 µg n=195 Participants Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg OD via a DPI followed by one inhalation of UMEC 62.5 µg administered via a DPI in the morning for 12weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms.	FF/VI 100/25 µg + UMEC 125 µg n=189 Participants Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg OD via a DPI followed by one inhalation of UMEC 125 µg administered via a DPI in the morning for 12 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms.
Change From Baseline in Weighted Mean (WM), 0-6 Hour FEV1 Obtained Post-dose at Day 84	0.034 Liters Standard Error 0.0123	0.187 Liters Standard Error 0.0122	0.175 Liters Standard Error 0.0123

Adverse Events

FF/VI 100/25 µg + Placebo

Serious events: 6 serious events

Other events: 15 other events

Deaths: 0 deaths

FF/VI 100/25 µg + UMEC 62.5 µg

Serious events: 2 serious events

Other events: 26 other events

Deaths: 0 deaths

FF/VI 100/25 µg + UMEC 125 µg

Serious events: 7 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	FF/VI 100/25 µg + Placebo n=206 participants at risk Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg OD via a DPI, followed by one inhalation of UMEC matching placebo, administered via a DPI in the morning for 12weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms.	FF/VI 100/25 µg + UMEC 62.5 µg n=206 participants at risk Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg OD via a DPI followed by one inhalation of UMEC 62.5 µg administered via a DPI in the morning for 12weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms.	FF/VI 100/25 µg + UMEC 125 µg n=207 participants at risk Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg OD via a DPI followed by one inhalation of UMEC 125 µg administered via a DPI in the morning for 12 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms.
Infections and infestations Nasopharyngitis	3.4% 7/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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.	3.4% 7/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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.	4.8% 10/207 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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 Headache	2.9% 6/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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.	4.4% 9/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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.	4.3% 9/207 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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 Back pain	1.5% 3/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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.	3.4% 7/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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.	2.4% 5/207 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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.
Respiratory, thoracic and mediastinal disorders Cough	0.49% 1/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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.	1.5% 3/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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.	3.4% 7/207 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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	FF/VI 100/25 µg + Placebo n=206 participants at risk Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg OD via a DPI, followed by one inhalation of UMEC matching placebo, administered via a DPI in the morning for 12weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms.	FF/VI 100/25 µg + UMEC 62.5 µg n=206 participants at risk Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg OD via a DPI followed by one inhalation of UMEC 62.5 µg administered via a DPI in the morning for 12weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms.	FF/VI 100/25 µg + UMEC 125 µg n=207 participants at risk Participants received one inhalation of fluticasone furoate/vilanterol 100/25 µg OD via a DPI followed by one inhalation of UMEC 125 µg administered via a DPI in the morning for 12 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study, for symptomatic relief from COPD symptoms.
Cardiac disorders Cardio-respiratory arrest	0.49% 1/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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% 0/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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% 0/207 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.49% 1/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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% 0/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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.	1.9% 4/207 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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	0.97% 2/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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% 0/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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% 0/207 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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 Influenza	0.00% 0/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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% 0/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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.	0.48% 1/207 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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 Klebsiella sepsis	0.00% 0/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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% 0/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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.	0.48% 1/207 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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% 0/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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% 0/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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.	0.48% 1/207 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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 failure congestive	0.00% 0/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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% 0/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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.	0.48% 1/207 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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	0.49% 1/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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% 0/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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% 0/207 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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) Lung neoplasm	0.00% 0/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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% 0/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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.	0.48% 1/207 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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) Lung neoplasm malignant	0.00% 0/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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.	0.49% 1/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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% 0/207 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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) Rectal cancer	0.49% 1/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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% 0/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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% 0/207 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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% 0/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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.	0.48% 1/207 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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.
Hepatobiliary disorders Hepatic congestion	0.00% 0/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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% 0/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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.	0.48% 1/207 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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 Shunt stenosis	0.49% 1/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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% 0/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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% 0/207 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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 Grand mal convulsion	0.00% 0/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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.	0.49% 1/206 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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% 0/207 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study medication until follow-up visit (up to 14 weeks) On-treatment SAEs and non-serious AEs are reported for members 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.