A 4-week Dose-Ranging, Dose-Interval, Efficacy, Safety and Tolerability Study of GSK961081 in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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This study is primarily designed to assess the dose response, dose interval, efficacy and safety of three once daily (QD) doses (100mcg, 400mcg and 800mcg) and three twice daily (BID) doses (100mcg, 200mcg and 400mcg,) of GSK961081 administered via DISKUS™ for 28 days in subjects with moderate/severe COPD versus placebo. Salmeterol 50mcg BID is included in the study as an active comparator.

Detailed Description
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This is a phase IIb multicentre, randomised, double-blind, double-dummy, placebo- and active-controlled, parallel-group, dose-ranging and dose-interval study. Eligible subjects will enter a seven-day run-in period followed by 28 days of double-blind, double-dummy treatment via the DISKUS inhaler. The study will consist of 8 visits, mainly conducted on an outpatient basis, 6 of which will be clinic visits and 2 of which will be phone contacts, including a post-treatment visit to follow up any adverse events. There will be approximately 425 subjects randomised to the study.

Official Title
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A 4-week Dose-Ranging, Dose-Interval, Efficacy, Safety and Tolerability Study of GSK961081 in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: GSK961081
* Drug: Salmeterol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Outpatient Subjects Subjects who give their signed and dated informed consent to participate 40 or more years of age, inclusive, at Visit 1 Male or females Subjects with an established clinical history of COPD Current or previous cigarette smokers with a history of ≥ 10 pack-years of cigarette smoking Subjects with the following liver function test values: Subjects with a measured post-salbutamol FEV1/FVC ratio of < 0.70 at Visit 1 (Screening). Subjects with a measured post-salbutamol FEV1 30-70% of predicted normal values Exclusion Criteria: Women who are pregnant or lactating or are planning to become pregnant during the study. Current diagnosis of asthma Other significant respiratory disorders besides COPD, including alpha-1 deficiency Previous lung resection surgery Significant abnormalities in chest x-ray presentation Hospitalization for a COPD exacerbation within 12 weeks prior screening Use of oral corticosteroids or antibiotics for COPD or antibiotics for a lower respiratory tract infection within 6 weeks Any significant disease that would put subject at risk through study participation BMI greater than 35 Pacemaker Significantly abnormal ECG, clinical lab finding (including Hepatitis B or C) Cancer Allergy or hypersensitivity to beta adrenergic receptor-agonist, sympathomimetic, anticholinergic/anti-muscarinic receptor antagonist, or inhaler excipients Diseases that would contra-indicate the use of anticholinergics Use of sysemic corticosteroids within 6 weeks of screening Use of long-acting beta-agonists within 48 hours of screening Use of tiotropium within 7 days of screening Use of theophyllines or anti-leukotrienes within 48 hours of screening Use of short-acting bronchodilators within 4 hours of screening Use of investigational medicines within 30 days of screening Use of high dose inhaled corticosteroids Use of long-term oxygen therapy, CPAP or NIPPV Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit 1 Regular (q.i.d or greater) use of short acting bronchodilators, including nebulized therapy Affiliation with Investigator Site Questionable Validity of Consent Previous use of GSK961081

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK961081 100 mcg QD<br> | Drug: GSK961081<br>* Comparison of different doses and dosing regimens of the drug<br>|
| Experimental: GSK961081 100mcg BD<br> | Drug: GSK961081<br>* Comparison of different doses and dosing regimens of the drug<br>|
| Experimental: GSK961081 200mcg QD<br> | Drug: GSK961081<br>* Comparison of different doses and dosing regimens of the drug<br>|
| Experimental: GSK961081 400mcg QD<br> | Drug: GSK961081<br>* Comparison of different doses and dosing regimens of the drug<br>|
| Experimental: GSK961081 400mcg BD<br> | Drug: GSK961081<br>* Comparison of different doses and dosing regimens of the drug<br>|
| Experimental: GSK961081 800mcg QD<br> | Drug: GSK961081<br>* Comparison of different doses and dosing regimens of the drug<br>|
| Active Comparator: Salmeterol 50mcg BD<br> | Drug: Salmeterol<br>* Positive control<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in FEV1 from baseline in pre-dose AM trough. | Pre-dose change in AM FEV1 on day 29 vs baseline . (defined as the mean values recorded 11 and 12 hours after the PM dose on day 28) | 28 Day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weighted Mean and Serial FEV1 at multiple timepoints | In the subset of patients with overnight spirometry on day 28 (pre-dose and post dose after 15,30, and 60 min and 2, 4,6, 11 and 12 hours) | 28 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lung function, bronchodilator, COPD, dose response, dosing interval, efficacy, safety, PD, PK