Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
lung function, bronchodilator, COPD, dose response, dosing interval, efficacy, safety, PD, PK
Brief summary
This study is primarily designed to assess the dose response, dose interval, efficacy and safety of three once daily (QD) doses (100mcg, 400mcg and 800mcg) and three twice daily (BID) doses (100mcg, 200mcg and 400mcg,) of GSK961081 administered via DISKUS™ for 28 days in subjects with moderate/severe COPD versus placebo. Salmeterol 50mcg BID is included in the study as an active comparator.
Detailed description
This is a phase IIb multicentre, randomised, double-blind, double-dummy, placebo- and active-controlled, parallel-group, dose-ranging and dose-interval study. Eligible subjects will enter a seven-day run-in period followed by 28 days of double-blind, double-dummy treatment via the DISKUS inhaler. The study will consist of 8 visits, mainly conducted on an outpatient basis, 6 of which will be clinic visits and 2 of which will be phone contacts, including a post-treatment visit to follow up any adverse events. There will be approximately 425 subjects randomised to the study.
Interventions
DRUGGSK961081
Comparison of different doses and dosing regimens of the drug
DRUGSalmeterol
Positive control
DRUGPlacebo
Placebo arm
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Outpatient Subjects * Subjects who give their signed and dated informed consent to participate * 40 or more years of age, inclusive, at Visit 1 * Male or females * Subjects with an established clinical history of COPD * Current or previous cigarette smokers with a history of ≥ 10 pack-years of cigarette smoking * Subjects with the following liver function test values: * Subjects with a measured post-salbutamol FEV1/FVC ratio of \< 0.70 at Visit 1 (Screening). * Subjects with a measured post-salbutamol FEV1 30-70% of predicted normal values
Exclusion criteria
* Women who are pregnant or lactating or are planning to become pregnant during the study. * 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 * Hospitalization for a COPD exacerbation within 12 weeks prior screening * Use of oral corticosteroids or antibiotics for COPD or antibiotics for a lower respiratory tract infection within 6 weeks * Any significant disease that would put subject at risk through study participation * BMI greater than 35 * Pacemaker * Significantly abnormal ECG, clinical lab finding (including Hepatitis B or C) * Cancer * Allergy or hypersensitivity to beta adrenergic receptor-agonist, sympathomimetic, anticholinergic/anti-muscarinic receptor antagonist, or inhaler excipients * Diseases that would contra-indicate the use of anticholinergics * Use of sysemic corticosteroids within 6 weeks of screening * Use of long-acting beta-agonists within 48 hours of screening * Use of tiotropium within 7 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 * Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit 1 * Regular (q.i.d or greater) use of short acting bronchodilators, including nebulized therapy * Affiliation with Investigator Site * Questionable Validity of Consent * Previous use of GSK961081
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in FEV1 from baseline in pre-dose AM trough. | 28 Day | Pre-dose change in AM FEV1 on day 29 vs baseline . (defined as the mean values recorded 11 and 12 hours after the PM dose on day 28) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Weighted Mean and Serial FEV1 at multiple timepoints | 28 Days | In the subset of patients with overnight spirometry on day 28 (pre-dose and post dose after 15,30, and 60 min and 2, 4,6, 11 and 12 hours) |
Countries
Estonia, Germany, Netherlands, Romania, Russia, Slovakia, South Africa, Sweden, Ukraine
Outcome results
None listed