28-day Repeat Dose Study of GSK573719

Study Overview
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Brief Summary
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The study will evaluate the efficacy, safety, and pharmacokinetics of GSK573719 compared with placebo in subjects with COPD

Detailed Description
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This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate 3 doses of GSK573719 administered once-daily over 28 days in subjects with COPD.

Official Title
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A Randomized, Double-blind, Parallel-group, Placebo-controlled Study to Evaluate the Efficacy and Safety of GSK573719 Delivered Once-daily Over 28 Days in Subjects With COPD

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: GSK573719 125mcg
* Drug: GSK573719 250mcg
* Drug: GSK573719 500mcg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A signed and dated written informed consent prior to study participation Males or females of non-childbearing potential 40 to 80 years of age COPD diagnosis 10 pack-years history or greater of cigarette smoking Post-bronchodilator FEV1/FVC ratio of 0.70 or less Post-bronchodilator FEV1 of 25 to 70% of predicted normal Exclusion Criteria: Asthma Other significant respiratory disorders besides COPD, including alpha-1 deficiency Previous lung resection surgery Chest X-ray or CP scan showing clinically significant abnormalities not due to COPD Use of oral steroids or antibiotics for a COPD exacerbation within 6 weeks of screening Hospitalization for COPD or pneumonia within 3 months of screening Any significant disease that would put subject at risk through study participation BMI greater than 35 Pacemaker Significantly abnormal ECG or clinical lab finding (including Hepatitis B or C) Cancer Allergy or hypersensitivity to anticholinergics or inhaler excipients Diseases that would contraindicate the use of anticholinergics Use of oral corticosteroids within 6 weeks of screening Use of long-acting beta-agonists within 48 hours of screening Use of tiotropium within 14 days of screening Use of theophyllines or anti-leukotrienes within 48 hours of screening Use of short-acting bronchodilators within 4 to 6 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 acute phase of pulmonary rehabilitation program History of alcohol or drug abuse within 2 years prior to screening History of psychiatric disease limiting validity of consent Affiliation with the investigative site Previous use of GSK573719

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: GSK573719 125mcg<br>125mcg once-daily via novel dry powder inhaler | Drug: GSK573719 125mcg<br>* 125mcg once-daily<br>|
| Experimental: GSK573719 250mcg<br>250mcg once-daily via novel dry powder inhaler | Drug: GSK573719 250mcg<br>* 250mcg once-daily<br>|
| Experimental: GSK573719 500mcg<br>500mcg once-daily via novel dry powder inhaler | Drug: GSK573719 500mcg<br>* 500mcg once-daily<br>|
| Placebo Comparator: Placebo<br>once-daily via novel dry powder inhaler | Drug: Placebo<br>* once-daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 29 | 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 Treatment Day 29 is defined as the mean of the FEV1 values obtained at 23 and 24 hours after dosing on Day 28. Baseline is defined as the mean of the FEV1 values obtained at 30 minutes and immediately pre-dose on Day 1. Change from Baseline is defined as the difference between trough on Day 29 and Baseline. Analysis was performed using a repeated measures model with covariates of Baseline (BL), country, sex, age, treatment, smoking status, day, day by Baseline interaction, and day by treatment interaction. | Baseline and Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Weighted Mean 0-6 Hour FEV1 Obtained Post-dose at 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. The weighted mean FEV1 was derived by calculating the area under the FEV1/time curve (AUC), and then dividing the value by the time interval over which the AUC was calculated. The weighted mean was calculated using the 0-6 hour post-dose measurements at Days 1 and 28, which included pre-dose (30 minutes prior to dosing on Day 1, or 24 hours after the previous day's dose on Day 28), and post-dose at 15 minutes, 30 minutes, 1 hour, 3 hours, and 6 hours. Baseline is defined as the mean of the FEV1 values obtained at 30 minutes and immediately pre-dose on Day 1. Change from Baseline is defined as the difference between weighted mean at Days 1 and 28 and Baseline. Analysis was performed using a repeated measures model with covariates of Baseline, country, sex, age, treatment, smoking status, day, day by Baseline interaction, and day by treatment interaction. | Baseline, Day 1, and Day 28 | 
| Change From Baseline in Serial FEV1 Over 24 Hours After Dosing at Day 1 and Day 28 | Serial spirometry assessments were conducted on Day 1 and Day 28 over the course of 24 hours and were obtained 0 (Day 28 only), 1, 3, 6, 23, and 24 hours after dosing. Baseline is defined as the mean of the FEV1 values obtained at 30 minutes and immediately pre-dose on Day 1. Change from Baseline is defined as the difference between FEV1 on Days 1 and 28 and Baseline. | Baseline, Day 1, and Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Bronchitis, Anticholinergic, Emphysema, Long-acting muscarinic antagonist, COPD