201211

GlaxoSmithKline

980 Great West Road, Brentford, Middlesex, United Kingdom,

GSK Response Center, GlaxoSmithKline, 1 866-435-7343,

GSK Response Center, GlaxoSmithKline, 1 866-435-7343,

No

No

No

Final

22 Apr 2015

No

Yes

05 Mar 2015

No

The primary objective of the study is to evaluate the effect of once-daily UMEC/VI 62.5/25mcg on health-related quality of life as measured using SGRQ total score compared to once-daily placebo in subjects with COPD.

To protect trial subjects, subjects were provided with supplemental salbutamol as rescue medication and the concurrent use of inhaled corticosteroids was allowed as maintenance treatment for COPD. Subjects enrolled in the study had stable disease with no hospitalization for COPD within at least 12 weeks of screening and no use of systemic corticosteroids or antibiotics for a lower respiratory tract infection for at least 6 weeks prior to screening. Subjects performed an ECG at screening to rule out significant cardiovascular abnormalities, and had a physical examination at the beginning and end of the study to assess health status. Frequent assessment of adverse events and COPD exacerbations was obtained during the study at clinical visits conducted 1 day following the first dose of study medication and every 4 weeks thereafter to ensure patients safety was closely monitored.

15 Sep 2014

No

No

Bulgaria: 78

Germany: 67

Hungary: 97

Romania: 69

Ukraine: 66

United States: 159

Russian Federation: 91

627

311

0

0

0

0

0

0

336

289

2

12-Week Treatment Period (overall period)

Randomised - controlled

Yes

Placebo

Inhalation powder

Inhalation use

Dry white powder delivered via DPI (2 strips with 30 blisters each, first containing lactose + magnesium stearate per blister and the second containing lactose per blister), administered as one inhalation of placebo, once daily in the morning

Umeclidinium/Vilanterol (UMEC/VI)

Inhalation powder

Inhalation use

Dry white powder delivered via dray powder inhaler (DPI; 2 strips with 30 blisters each, first containing UMEC 62.5 mcg + lactose per blister and second containing VI 25 mcg + lactose + magnesium stearate per blister), administered as one inhalation of UMEC/VI 62.5/25 mcg, once daily in the morning

Placebo

UMEC/VI 62.5/25 mcg

Placebo

UMEC/VI 62.5/25 mcg

The SGRQ is a disease-specific questionnaire, self-completed by participants(par), to evaluate the effect of UMEC/VI on health-related quality of life as compared to placebo in par with COPD. The SGRQ contains 76 items grouped into three domains (symptoms, activity, impacts) and scores range from 0 (minimum, best possible health status) to 100 (maximum, worst possible health status). 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 was calculated as the SGRQ total score at a particular visit minus Baseline. Change from Baseline in total score of -4 units or lower is considered as clinically meaningful improvement in quality of life. Intent-to-Treat (ITT) Population included par who received at least one dose of randomized study drug.

Primary

Baseline and Day 84

Participants 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.

UMEC/VI 62.5/25 mcg v Placebo

422

Pre-specified

-4.03

2-sided

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. Intent-to-Treat (ITT) Population included par 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 analysis

Secondary

Baseline and Day 84

UMEC/VI 62.5/25 mcg v Placebo

451

Pre-specified

0.122

2-sided

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 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. ITT population was analyzed.

Secondary

Week 1 to Week 12

Participants represent all participants in the ITT population without missing covariate information and with at least one post BL measurement.

UMEC/VI 62.5/25 mcg v Placebo

491

Pre-specified

-0.7

2-sided

On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug until 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.

17.1

UMEC/VI 62.5/25mcg

Placebo