Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the Combination of GSK573719 and GW642444 in Subjects With COPD

Study Overview
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Brief Summary
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The study will evaluate safety, tolerability, pharmacokinetics and pharmacodynamics of the combination of inhaled GSK573719 and GW64244 compared to 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 the safety and tolerability of the combination of GSK573719 (500mcg) Inhalation Powder and GW642444 (25mcg) Inhalation Powder administered once-daily via a novel dry powder inhaler (Novel DPI) over 28 days in subjects with COPD

Official Title
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Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the Combination of GSK573719 and GW642444 in Subjects With COPD

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: 500mcg/25mcg once daily
* Drug: Placebo once daily


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 or more 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 80% or less of predicted normal Exclusion Criteria: 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 Use of oral steroids, antibiotics or hospitalization for a COPD exacerbation within 3 motnhs prior screening Any significant disease that would put subject at risk through study participation BMI greater than 35 Pacemaker Significantly abnormal ECG, Holter, or clinical lab finding (including Hepatitis B or C) Cancer Allergy or hypersensitivity to anticholinergics or inhaler excipients Diseases that would contra-indicate 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 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 Previous use of GSK573719 or GW642444

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: GSK573719/GW642444<br> | Drug: 500mcg/25mcg once daily<br>* GSK573719/GW642444<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo once daily<br>* Inactive, excipients only<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 to 6 Hours Post-dose at Day 28 | Pulse rate is defined as the number of heartbeats in a minute. The weighted mean pulse rate was derived by calculating the area under the pulse rate/time curve (AUC), and then dividing the value by the time interval over which the AUC was calculated. The weighted mean pulse rate was calculated using the 0 to 6 hours post dose measurements at Day 28, which included pre-dose, and post-dose 15 minutes, 45 minutes, 1.5 hours, 3 hours and 6 hours. Baseline pulse rate is the most recent result taken on or before pre-dose Day 1. Change from Baseline is the weighted mean pulse rate at Day 28 minus the Baseline value. Analysis was performed using a repeated measures model with covariates of Baseline pulse rate, sex, age, smoking status, treatment and day and day by treatment and day by Baseline interactions. | Baseline and Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Weighted Mean Pulse Rate Over 0 to 6 Hours Post-dose at Day 1 and Day 14 | Pulse rate is defined as the number of heartbeats in a minute. The weighted mean pulse rate was derived by calculating the area under the pulse rate/time curve (AUC) using the trapezoidal rule, and then dividing the value by the time interval over which the AUC was calculated. The weighted mean pulse rate was calculated using the 0 to 6 hours post dose measurements on Day 1 and Day 14, which included pre-dose, and post-dose 15 minutes, 45 minutes, 1.5 hours, 3 hours and 6 hours. Baseline pulse rate is the most recent result taken on or before pre-dose Day 1. Change from Baseline is the weighted mean pulse rate at Day 1 or Day 14 minus the Baseline value. Analysis was performed using a repeated measures model with covariates of Baseline pulse rate, sex, age, smoking status, treatment and day and day by treatment and day by Baseline interactions. | Baseline, Day 1, and Day 14 | 
| Change From Baseline in Maximum and Minimum Pulse Rate 0 to 6 Hours Post-dose on Days 1, 14, and 28 | Pulse rate is defined as the number of heartbeats in a minute (m). A maximum post-Baseline pulse rate was derived as the maximum value recorded at Days 1, 14 and 28. A minimum post-Baseline pulse rate was derived as the minimum value recorded at Days 1, 14 and 28. The maximum and minimum pulse rates were calculated using the 0 to 6 hours (h) post dose measurements on Days 1, 14 and 28, which included pre-dose, and post-dose 15 m, 45 m, 1.5 h, 3 h and 6 h. Maximum and minimum post-Baseline rate were calculated using the nominal 0-6 h post-dose records, and only records collected during the actual 0-7 h post-dose interval were used. Baseline pulse rate is the most recent result taken on or before pre-dose Day 1. Change from Baseline is the maximum or minimum pulse rate minus the Baseline value. Analysis performed using a repeated measures model with covariates of Baseline pulse rate, sex, age, smoking status, treatment and day and day by treatment and day by Baseline interactions. | Baseline, Day 1, Day 14 and Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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long-acting beta2-receptor agonist, Safety and tolerability, pharmacodynamics, pharmacokinetics, long-acting muscarinic receptor antagonist, COPD