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

Phase 2

Completed

Conditions: Pulmonary Disease, Chronic Obstructive

Interventions: Drug: 500mcg/25mcg once daily
Drug: Placebo once daily

Registration Number: NCT01039675

Lead Sponsor: GlaxoSmithKline

Brief Summary: 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: 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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 51

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GSK573719/GW642444	500mcg/25mcg once daily	-
Placebo	Placebo once daily	-

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Weighted Mean Pulse Rate Over 0 to 6 Hours Post-dose at Day 28	Baseline and 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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Weighted Mean Pulse Rate Over 0 to 6 Hours Post-dose at Day 1 and Day 14	Baseline, 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.
Change From Baseline in Maximum and Minimum Pulse Rate 0 to 6 Hours Post-dose on Days 1, 14, and 28	Baseline, Day 1, Day 14 and Day 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.