Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
COPD, long-acting beta agonist, Emphysema, Chronic Bronchitis, Chronic Obstructive Pulmonary Disease (COPD), bronchodilator, long acting muscarinic antagonist
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.
Interventions
DRUGPlacebo
matching placebo
DRUGGSK233705/GW642444
The combination of the long-acting muscarinic antagonist GSK233705 and the long acting beta agonist GW642444 in a single inhaler.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
This study was conducted between 13 November 2008 and 12 February 2009, at 12 centers in the United States.
Pre-assignment details
A total of 127 participants were screened out of which 61 participants were enrolled and randomized to receive at least one dose of study medication in the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Eligible participants received oral inhalation of matching Placebo via DPI once daily for 28 days. | 21 |
| GSK233705/GW642444 Eligible participants received oral inhalation of GSK233705 100 mcg / GW642444 25 mcg via DPI once daily for 28 days. | 40 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Protocol-defined stopping criteria | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | GSK233705/GW642444 | Total |
|---|---|---|---|
| Age, Continuous | 60.7 Years STANDARD_DEVIATION 10.09 | 61.2 Years STANDARD_DEVIATION 9.55 | 61.0 Years STANDARD_DEVIATION 9.66 |
| Race/Ethnicity, Customized African American / African Heritage | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 20 Participants | 38 Participants | 58 Participants |
| Sex: Female, Male Female | 10 Participants | 11 Participants | 21 Participants |
| Sex: Female, Male Male | 11 Participants | 29 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 40 |
| other Total, other adverse events | 8 / 21 | 10 / 40 |
| serious Total, serious adverse events | 0 / 21 | 0 / 40 |
Outcome results
Primary
Change From Baseline in Weighted Mean Pulse Rate Over (0-4 Hours) at 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).
Time frame: Baseline (Pre-dose, Day 1) and Day 28
Population: Intent-to-Treat (ITT) Population comprised of all participants who were randomized to study treatment and took at least one dose of study medication. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Weighted Mean Pulse Rate Over (0-4 Hours) at Day 28. | -3.8 Beat per minute (bpm) | Standard Error 1.78 |
| GSK233705/GW642444 | Change From Baseline in Weighted Mean Pulse Rate Over (0-4 Hours) at Day 28. | -4.8 Beat per minute (bpm) | Standard Error 1.32 |
95% CI: [-5.5, 3.5]
Secondary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
Time frame: On-treatment; from treatment start until one day after treatment stop (Up to Day 29)
Population: ITT Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 8 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |
| GSK233705/GW642444 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 10 Participants |
| GSK233705/GW642444 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |