Safety and Tolerability of Repeat Dosing of GSK233705/GW642444 in COPD

Study Overview
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Brief Summary
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The purpose of this study is the evaluate the safety and tolerability of repeat dosing of the combination of inhaled GSK233705 and GW642444 administered once-daily in subjects with COPD.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, 4-week Study to Evaluate the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Repeat Inhaled Doses of the Combination of GSK233705 and GW642444 Administered Once-daily in Subjects With COPD

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: Placebo
* Drug: GSK233705/GW642444


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male and females 40 to 80 years of age (inclusive) COPD diagnosis Current or previous smokers with a cigarette smoking history of at least 10 pack- Post-albuterol FEV1/FVC of 0.70 or less Post-albuterol FEV1 of 35% to 80% (inclusive) Exclusion Criteria: Pregnant or lactating females current diagnosis of asthma respiratory disorders other than COPD clinically significant cardiovascular, neurological, psychiatric, renal, immunological, endocrine, or hematological abnormalities that are uncontrolled clinically significant sleep apnea previous lung resection surgery clinically significant abnormalities confirmed by chest x-ray that are not related to COPD hospitalization for COPD within 3 months of screening use of antibiotics for lower respiratory tract infection within 6 months of screening abnormal and clinically significant 12-lead ECG findings current malignancy in remission for less that 5 years medical conditions that would contraindicate the use of anticholinergics positive hepatitis B or C test history of alcohol or drug abuse unable to withhold albuterol for 6 or more hours use of long term oxygen therapy conditions that would limit the validity of informed consent use of GW642444 or GSK233705 in previous studies use of an investigation drug with 30 days of screening use of inhaled corticosteroids (ICS) at a dose greater than 1000mcg of fluticasone propionate or equivalent hypersensitivity to beta-agonists concurrent use of long-acting beta-agonists (LABA) or long-acting muscaring antagonists, LABA/ICS combination products, cytochrome p450 inhibitors, oral or depot corticosteroids, theophyllines, oral beta agonists, oral leukotrine modulators, inhaled short acting anticholinergics.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Drug: GSK233705/GW642444<br>* The combination of the long-acting muscarinic antagonist GSK233705 and the long acting beta agonist GW642444 in a single inhaler.<br>|
| Placebo Comparator: Arm 2<br> | Drug: Placebo<br>* matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Weighted Mean Pulse Rate Over (0-4 Hours) at Day 28. | Baseline was the most recent result taken on or before pre-dose (Day 1). The analysis was performed using a Repeated Measures Model. This model used all available weighted mean pulse rate values recorded. Change from Baseline was calculated as (Change from Baseline = Assessment value - Baseline value). | Baseline (Pre-dose, Day 1) and Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE include AEs those result in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. | On-treatment; from treatment start until one day after treatment stop (Up to Day 29) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, long-acting beta agonist, Emphysema, Chronic Bronchitis, Chronic Obstructive Pulmonary Disease (COPD), bronchodilator, long acting muscarinic antagonist