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

Phase 2

Completed

Brief Summary: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Arm 1	GSK233705/GW642444	-
Arm 2	Placebo	-

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Weighted Mean Pulse Rate Over (0-4 Hours) at Day 28.	Baseline (Pre-dose, Day 1) and 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).

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	On-treatment; from treatment start until one day after treatment stop (Up to Day 29)	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.