NCT01636713|CompletedPhase 3Results

A 24-week Study to Evaluate the Efficacy and Safety of GSK573719/GW642444 125/25 mcg and 62.5/25mcg Inhalation Powder Compared With Placebo in Subjects With COPD

A 24-week Randomised, Double-blind and Placebo-controlled Study to Evaluate the Efficacy and Safety of GSK573719/GW642444 125/25 mcg and 62.5/25mcg Inhalation Powder Compared With Placebo Inhalation Powder Delivered Once-daily Via a Novel Dry Powder Inhaler in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

GlaxoSmithKline ClinicalTrials.gov

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1 other identifier

114634

Study Type

interventional

Target

581

Locations

5 countries

Sites

Timeline

RegisteredJul 2012

StartedJul 2012

CompletionOct 2013

Brief Summary

This is a 24-week, phase III multicenter, randomized, double-blind, placebo-controlled, parallel-group study. The study will have 9 scheduled visits and a telephone contact Follow-up visit one week following the end of study treatment. The study primary endpoint is

Clinic visit trough (pre-bronchodilator and pre-dose) FEV1 on Treatment Day 169 Trough FEV1 on Treatment Day 169 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on Treatment Day 168 (i.e. at the Week 24 visit). Secondary endpoints are;
Mean TDI focal score at Week 24
Weighted mean clinic visit FEV1 over 0 to 6 hours post-dose at Visit 2 (Day 1) Eligible subjects will be randomised to GSK573719/GW642444 125/25mcg, GSK573719/GW642444 62.5/25mcg and placebo treatment groups in a 1:1:1 ratio such that of the planned 573 total number of randomised subjects, approximately 191 subjects will be randomised to each active treatment group and 191 subjects will be randomised to placebo. All treatments will be administered once daily in the morning by inhalation using a Novel Dry Powder Inhaler (NDPI). There will be a total of 9 study clinic visits conducted on an outpatient basis. Subjects who meet the eligibility criteria at Screening (Visit.1) will complete a 7 to 14 day Run-In period followed by a 24-week Treatment period. Clinic visits will be at screening, Randomisation (Day1), Day2, after 4, 8, 12, 16, and 24-weeks of treatment, and 1 day after the Week 24 Visit (also referred as Treatment Day 169). A Follow-Up contact for adverse event assessment will be conducted by telephone approximately 7 days after Visit 9 or the Early Withdrawal Visit. The total duration of subject participation, including Follow-up will be approximately 27 weeks. All subjects will be provided with albuterol/salbutamol for use on an "as-needed" basis throughout the Run-In and Study Treatment Periods. At screening, pre-bronchodilator spirometry will be performed followed by post-albuterol/salbutamol spirometry testing. Post-albuterol/salbutamol FEV1 and FEV1/FVC values will be used to determine subject eligibility. To further characterise bronchodilator responsiveness, post ipratropium testing will be conducted following completion of post-albuterol/salbutamol spirometry. Spirometry will be conducted at each post-randomisation clinic visit. Six hour post-dose serial spirometry will be conducted at Visit 2. Trough spirometry will be obtained 23 and 24 hours after the previous day's dose of blinded study medication at Visits 3 to 9. Assessments of dyspnea will be obtained using the Baseline and Transition Dyspnoea Index (BDI/TDI) which is an interviewer based instrument. At Visit 2, the severity of dyspnoea at baseline will be assessed using the BDI. At subsequent visits (Visits 4, 6, and 8) change from baseline will be assessed using the TDI. Administration of the BDI and TDI should be done prior to spirometry and any other study-related procedures Disease specific health status will be evaluated using the St. George's Respiratory Questionnaire (SGRQ) and COPD Assessment Test (CAT), at baseline (Visit 2) and Visits 4, 6 and 8. The occurrence of adverse events will be evaluated throughout the study beginning at Visit 2. SAEs will be collected over the same time period as for AEs. However, any SAEs assessed as related to study participation (e.g., study treatment, protocol-mandated procedures, invasive tests, or change in existing therapy) or related to a GSK concomitant medication, will be recorded from the time a subject consents to participate in the study up to and including any follow up contact. Vital signs (blood pressure and pulse rate), 12-lead ECGs and standard clinical laboratory tests (hematology and blood biochemistry) will be obtained at selected clinic visits. For determination of subject disposition, subjects will be considered to have completed the study, upon completion of Visit 9. There is no plan to provide any of the active study treatments for compassionate use following study completion. The Intent-to-Treat (ITT) population will be the primary population of interest, and is defined as all randomised subjects who have received at least one dose of the randomised study medication during the Treatment Period. Supplementary study conduct information not mandated to be present in this protocol is provided in the accompanying Study Procedures Manual (SPM). The SPM will provide the site personnel with administrative and detailed technical information that does not impact subject safety.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

581

participants targeted

Target at P75+ for phase_3

Timeline

Completed

Started Jul 2012

Shorter than P25 for phase_3

Geographic Reach

5 countries

44 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

1.3 years study duration

Study Start

First participant enrolled

July 1, 2012

Completed

4 days until next milestone

First Submitted

Initial submission to the registry

July 5, 2012

Completed

5 days until next milestone

First Posted

Study publicly available on registry

July 10, 2012

Completed

1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2013

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2013

Completed

9 months until next milestone

Results Posted

Study results publicly available

June 24, 2014

Completed

Last Updated

January 9, 2017

Status Verified

November 1, 2016

Enrollment Period

1.3 years

First QC Date

July 5, 2012

Results QC Date

May 1, 2014

Last Update Submit

November 18, 2016

Conditions

Pulmonary Disease, Chronic Obstructive

Outcome Measures

Primary Outcomes (1)

Change From Baseline (BL) in Trough Forced Expiratory Volume in One Second (FEV1) on Day 169 (Week 24)
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 2, 28, 56, 84, 112, 168, and 169. Baseline is defined as the mean of the assessments made 30 minutes pre-dose and 5 minutes pre-dose on Treatment Day 1. Trough FEV1 is defined as the mean of the FEV1 values obtained at 23 and 24 hours after the previous morning's dosing (ie., trough FEV1 on Day 169 is the mean of the FEV1 values obtained 23 and 24 hours after the morning dosing on Day 168). Change from Baseline at a particular visit was calculated as the trough FEV1at that visit minus Baseline. Analysis was performed using a repeated measures model with covariates of treatment, Baseline, smoking status, country/region, day, day by Baseline and day by treatment interactions. par.=participants.
Baseline and Day 169

Secondary Outcomes (2)

Transition Dyspnea Index (TDI) Focal Score at Day 168 (Week 24)
Day 168 (Week 24)
Change From Baseline Weighted Mean (WM) 0-6 Hour FEV1 Obtained Post-dose at Day 1
Baseline and Day 1