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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01319019
First received: March 3, 2011
Last updated: July 31, 2014
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: GSK961081
Drug: Salmeterol
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A 4-week Dose-Ranging, Dose-Interval, Efficacy, Safety and Tolerability Study of GSK961081 in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Change in FEV1 from baseline in pre-dose AM trough. [ Time Frame: 28 Day ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Weighted Mean and Serial FEV1 at multiple timepoints [ Time Frame: 28 Days ] [ Designated as safety issue: No ]
    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)


Enrollment: 437
Study Start Date: December 2010
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK961081 100 mcg QD Drug: GSK961081
Comparison of different doses and dosing regimens of the drug
Experimental: GSK961081 100mcg BD Drug: GSK961081
Comparison of different doses and dosing regimens of the drug
Experimental: GSK961081 200mcg QD Drug: GSK961081
Comparison of different doses and dosing regimens of the drug
Experimental: GSK961081 400mcg QD Drug: GSK961081
Comparison of different doses and dosing regimens of the drug
Experimental: GSK961081 400mcg BD Drug: GSK961081
Comparison of different doses and dosing regimens of the drug
Experimental: GSK961081 800mcg QD Drug: GSK961081
Comparison of different doses and dosing regimens of the drug
Active Comparator: Salmeterol 50mcg BD Drug: Salmeterol
Positive control
Placebo Comparator: Placebo Drug: Placebo
Placebo arm

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.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01319019

  Show 49 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01319019     History of Changes
Other Study ID Numbers: 115032
Study First Received: March 3, 2011
Last Updated: July 31, 2014
Health Authority: United States: Food and Drug Administration
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by GlaxoSmithKline:
lung function
bronchodilator
COPD, dose response, dosing interval, efficacy, safety, PD, PK

Additional relevant MeSH terms:
Chronic Disease
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Disease Attributes
Pathologic Processes
Respiratory Tract Diseases
Salmeterol
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014