28-day Repeat Dose Study of GSK573719

Phase 2

Completed

Conditions: Pulmonary Disease, Chronic Obstructive

Interventions: Drug: GSK573719 125mcg
Drug: GSK573719 250mcg
Drug: GSK573719 500mcg
Drug: Placebo

Registration Number: NCT01030965

Lead Sponsor: GlaxoSmithKline

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

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 285

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GSK573719 125mcg	GSK573719 125mcg	125mcg once-daily via novel dry powder inhaler
GSK573719 250mcg	GSK573719 250mcg	250mcg once-daily via novel dry powder inhaler
GSK573719 500mcg	GSK573719 500mcg	500mcg once-daily via novel dry powder inhaler
Placebo	Placebo	once-daily via novel dry powder inhaler

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 29	Baseline and 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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Serial FEV1 Over 24 Hours After Dosing at Day 1 and Day 28	Baseline, 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.
Change From Baseline in Weighted Mean 0-6 Hour FEV1 Obtained Post-dose at Day 1 and Day 28	Baseline, 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.