A 4-week Dose-Ranging, Dose-Interval, Efficacy, Safety and Tolerability Study of GSK961081 in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 2

Conditions: Pulmonary Disease, Chronic Obstructive

Treatments: Drug: GSK961081; Drug: Salmeterol; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01319019

115032

Details and patient eligibility

About

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.

Full 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.

Enrollment: 437 patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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437 participants in 8 patient groups, including a placebo group

GSK961081 100 mcg QD

Experimental group

Treatment:

Drug: GSK961081

GSK961081 100mcg BD

Experimental group

Treatment:

Drug: GSK961081

GSK961081 200mcg QD

Experimental group

Treatment:

Drug: GSK961081

GSK961081 400mcg QD

Experimental group

Treatment:

Drug: GSK961081

GSK961081 400mcg BD

Experimental group

Treatment:

Drug: GSK961081

GSK961081 800mcg QD

Experimental group

Treatment:

Drug: GSK961081

Salmeterol 50mcg BD

Active Comparator group

Treatment:

Drug: Salmeterol

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo