Trial Outcomes & Findings for A Study To Assess Single Dosage Strength Of GW685698/GW642444 Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT00731822)

Last Updated: 2016-12-08

Results Overview

Co-Primary Endpoint. Weighted mean was derived by calculating the average area under the curve (AUC), and then dividing by the relevant time interval. Baseline is the most recent result taken on or before pre-dose Day 1. Heart rate was recorded at 60 minutes (min) prior to dosing and at 15 min, 45 min, 90 min, 120 min, and 240 min post-dose on Day 28. Change from Baseline was calculated as the Day 28 value minus the Baseline value. Analysis was performed using a restricted maximum likelihood (REML)-based repeated measures mixed model approach (MMRM) with covariates of Baseline heart rate, sex, age, smoking status, treatment, and day and day by treatment and day by Baseline interactions. par.=participants.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

60 participants

Primary outcome timeframe

Baseline to Day 28

Results posted on

2016-12-08

Participant Flow

Participants meeting eligibility criteria at screening and randomization criteria at the end of the Screening Period (SP) were randomized to 1 of 2 treatments: Fluticasone Furoate (FF)/Vilanterol (GW642444) 400/25 microgram (µg) inhalation powder or matching placebo. 89 participants were screened, of whom 60 were randomized.

Participant milestones

Participant milestones
Measure	Placebo Participants received matching placebo once daily (OD) in the morning via a dry powder inhaler (DPI) for 28 days.	FF/VI 400/25 µg OD Participants received fluticasone furoate (FF)/Vilanterol (VI \[GW642444\]) 400/25 micrograms (µg) OD in the morning via a DPI for 28 days.
Overall Study STARTED	20	40
Overall Study COMPLETED	16	39
Overall Study NOT COMPLETED	4	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received matching placebo once daily (OD) in the morning via a dry powder inhaler (DPI) for 28 days.	FF/VI 400/25 µg OD Participants received fluticasone furoate (FF)/Vilanterol (VI \[GW642444\]) 400/25 micrograms (µg) OD in the morning via a DPI for 28 days.
Overall Study Adverse Event	2	1
Overall Study Protocol Violation	1	0
Overall Study Lost to Follow-up	1	0

Baseline Characteristics

A Study To Assess Single Dosage Strength Of GW685698/GW642444 Chronic Obstructive Pulmonary Disease (COPD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=20 Participants Participants received matching placebo once daily (OD) in the morning via a dry powder inhaler (DPI) for 28 days.	FF/VI 400/25 µg OD n=40 Participants Participants received fluticasone furoate (FF)/Vilanterol (VI \[GW642444\]) 400/25 micrograms (µg) OD in the morning via a DPI for 28 days.	Total n=60 Participants Total of all reporting groups
Age, Continuous	63.8 Years STANDARD_DEVIATION 6.01 • n=5 Participants	63.5 Years STANDARD_DEVIATION 7.10 • n=7 Participants	63.6 Years STANDARD_DEVIATION 6.71 • n=5 Participants
Gender Female	5 Participants n=5 Participants	15 Participants n=7 Participants	20 Participants n=5 Participants
Gender Male	15 Participants n=5 Participants	25 Participants n=7 Participants	40 Participants n=5 Participants
Race/Ethnicity, Customized White	20 participants n=5 Participants	40 participants n=7 Participants	60 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Day 28

Population: Intent-to-Treat (ITT) Population: all randomized par. who received at least one dose of study medication. The number of par. presented represent those with data available at the time point being presented; however, all par. in the ITT Population without missing covariate information and with \>=1 post-BL measurement are included in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Participants received matching placebo once daily (OD) in the morning via a dry powder inhaler (DPI) for 28 days.	FF/VI 400/25 µg OD n=40 Participants Participants received fluticasone furoate (FF)/Vilanterol (VI \[GW642444\]) 400/25 micrograms (µg) OD in the morning via a DPI for 28 days.
Change From Baseline in Weighted Mean Heart Rate 0-4 Hours Post-dose at the End of the 28-day Treatment Period	-5.7 Beats per minute (bpm) Standard Error 1.83	-5.1 Beats per minute (bpm) Standard Error 1.23

PRIMARY outcome

Timeframe: From Baseline (Day 1) until Follow-up (up to Study Day 37)

Population: ITT Population

Co-Primary Endpoint. An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; or is a congenital anomaly/birth defect. See the SAE/AE module of this results summary for a list of specific SAEs/AEs occurring in the study.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Participants received matching placebo once daily (OD) in the morning via a dry powder inhaler (DPI) for 28 days.	FF/VI 400/25 µg OD n=40 Participants Participants received fluticasone furoate (FF)/Vilanterol (VI \[GW642444\]) 400/25 micrograms (µg) OD in the morning via a DPI for 28 days.
Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE) Throughout the Study Any SAE	0 participants	1 participants
Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE) Throughout the Study Any AE	10 participants	27 participants

SECONDARY outcome

Timeframe: Baseline; Day 2, Day 15, and Day 29

Population: ITT Population. The number of participants presented (indicated by n=X, X in the category titles) represents the number of participants with data available at that time point. 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. Trough FEV1 on Days 2, 15, and 29 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on Days 1, 14, and 28. The highest of 3 technically acceptable measurements was recorded. Baseline FEV1 is defined as the mean of the two assessments obtained 30 minutes pre-dose and immediately pre-dose on Day 1. Change from Baseline was calculated as the Day 29 value minus the Baseline value. Analysis was performed using Mixed Model Repeated Measures (MMRM) with covariates of Baseline FEV1, sex, age, smoking status, treatment and day, and day by treatment and day by Baseline interactions.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Participants received matching placebo once daily (OD) in the morning via a dry powder inhaler (DPI) for 28 days.	FF/VI 400/25 µg OD n=40 Participants Participants received fluticasone furoate (FF)/Vilanterol (VI \[GW642444\]) 400/25 micrograms (µg) OD in the morning via a DPI for 28 days.
Mean Change From Baseline in Clinic Visit Trough Forced Expiratory Volume in One Second (FEV1) on Days 2, 15, and 29 Day 2, n=20, 39	0.122 Liters Standard Error 0.0323	0.276 Liters Standard Error 0.0229
Mean Change From Baseline in Clinic Visit Trough Forced Expiratory Volume in One Second (FEV1) on Days 2, 15, and 29 Day 15, n=15, 39	0.113 Liters Standard Error 0.0387	0.285 Liters Standard Error 0.0253
Mean Change From Baseline in Clinic Visit Trough Forced Expiratory Volume in One Second (FEV1) on Days 2, 15, and 29 Day 29, n=16, 39	0.088 Liters Standard Error 0.0398	0.271 Liters Standard Error 0.0262

SECONDARY outcome

Timeframe: Baseline (pre-dose on Day 1); Day 1 and Day 28

FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Serial FEV1 measurements were taken electronically by spirometry at the Day 1 and Day 28 clinic visits (60 minutes pre-dose; immediately pre-dose; post-dose after 5, 15, and 30 minutes and 1, 2, and 4 hours. Weighted mean was calculated using the 24-hour serial FEV1 measurements that included the 0 to 4 hours post-dose assessment. At each time point, the highest of 3 technically acceptable measurements was recorded. Baseline FEV1 was defined as the mean of the two assessments obtained 30 minutes pre-dose and immediately pre-dose on Day 1. Change from Baseline was calculated as the average Day 28 FEV1 value minus the Baseline value. Analysis was performed using Mixed Model Repeated Measures (MMRM) with covariates of Baseline FEV1, sex, age, smoking status, treatment and day, and day by treatment and day by Baseline interactions.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Participants received matching placebo once daily (OD) in the morning via a dry powder inhaler (DPI) for 28 days.	FF/VI 400/25 µg OD n=40 Participants Participants received fluticasone furoate (FF)/Vilanterol (VI \[GW642444\]) 400/25 micrograms (µg) OD in the morning via a DPI for 28 days.
Mean Change From Baseline (Pre-dose on Day 1) in Weighted Mean FEV1 (0-4 Hours Post-dose) on Days 1 and 28 Day 1, n=20, 40	0.022 Liters Standard Error 0.0259	0.222 Liters Standard Error 0.0182
Mean Change From Baseline (Pre-dose on Day 1) in Weighted Mean FEV1 (0-4 Hours Post-dose) on Days 1 and 28 Day 28, n=16, 39	0.047 Liters Standard Error 0.0341	0.283 Liters Standard Error 0.0227

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

FF/VI 400/25 µg OD

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=20 participants at risk Participants received matching placebo once daily (OD) in the morning via a dry powder inhaler (DPI) for 28 days.	FF/VI 400/25 µg OD n=40 participants at risk Participants received fluticasone furoate (FF)/Vilanterol (VI \[GW642444\]) 400/25 micrograms (µg) OD in the morning via a DPI for 28 days.
Gastrointestinal disorders Colitis ulcerative	0.00% 0/20 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.	2.5% 1/40 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.

Other adverse events

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=20 participants at risk Participants received matching placebo once daily (OD) in the morning via a dry powder inhaler (DPI) for 28 days.	FF/VI 400/25 µg OD n=40 participants at risk Participants received fluticasone furoate (FF)/Vilanterol (VI \[GW642444\]) 400/25 micrograms (µg) OD in the morning via a DPI for 28 days.
Infections and infestations Nasopharyngitis	15.0% 3/20 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.	17.5% 7/40 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.
Infections and infestations Oral candidiasis	0.00% 0/20 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.	7.5% 3/40 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.
Infections and infestations Urinary tract infection	5.0% 1/20 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.	0.00% 0/40 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.
Nervous system disorders Headache	5.0% 1/20 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.	15.0% 6/40 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.
Nervous system disorders Dizziness	5.0% 1/20 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.	5.0% 2/40 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.
General disorders Chest pain	5.0% 1/20 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.	2.5% 1/40 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.
General disorders Pyrexia	5.0% 1/20 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.	0.00% 0/40 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/20 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.	5.0% 2/40 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.0% 1/20 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.	0.00% 0/40 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.
Skin and subcutaneous tissue disorders Erythema	5.0% 1/20 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.	0.00% 0/40 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.
Skin and subcutaneous tissue disorders Hyperhidrosis	5.0% 1/20 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.	0.00% 0/40 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.
Skin and subcutaneous tissue disorders Rash	5.0% 1/20 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.	0.00% 0/40 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.
Gastrointestinal disorders Dry mouth	5.0% 1/20 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.	0.00% 0/40 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.
Investigations Electrocardiogram abnormal	5.0% 1/20 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.	0.00% 0/40 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.
Musculoskeletal and connective tissue disorders Myalgia	5.0% 1/20 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.	0.00% 0/40 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the study treatment stop date (Day 28 +1). An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.