Effect of a New Combination Bronchodilator on Exercise in GOLD Stage II Moderate COPD

NCT ID: NCT01491802

Last Updated: 2017-08-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2014-09-30

Brief Summary

Preliminary information from our laboratory indicated that even patients with milder chronic obstructive pulmonary disease (COPD) can have significant physiological derangements which become more pronounced during exercise, leading to intolerable dyspnea at lower levels of ventilation than in health. This study will explore pathophysiological mechanisms of dyspnea and activity limitation in GOLD stage II COPD and will determine if there is a sound physiological rationale for the use of dual long-acting beta2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) therapy (GSK573719/ GW642444 Inhalation Powder) versus LAMA alone (GSK573719) as treatment for dyspnea and exercise intolerance in this subpopulation. Objectives of this study are to determine if: 1) neuromechanical uncoupling of the respiratory system contributes to exertional dyspnea in milder COPD, and 2) treatment with LABA/LAMA improves dyspnea and exercise endurance compared with LAMA by improving neuromechanical coupling. The investigators hypothesize that: 1) dyspnea is related to excessive dynamic lung hyperinflation, tidal volume restriction and increased ratio of central respiratory neural drive to tidal volume displacement, a measure of neuromechanical uncoupling of the respiratory system, and 2) LABA/LAMA will improve dyspnea and exercise endurance, which will be explained by partial reversal of the above mechanical abnormalities. The investigators will conduct a randomized, double-blind crossover study and compare the effects of once-daily LABA/LAMA over 4-weeks with LAMA on dyspnea, exercise endurance and ventilatory mechanics in GOLD stage II COPD.

Conditions

COPD

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

LAMA alone, then LAMA/LABA combination

Participants will first receive an inhaled long-acting muscarinic antagonist (LAMA) once daily for 4 weeks. After a 2 week washout period, they will then receive the fixed-dose combination product \[LAMA plus long-acting beta2-agonist (LABA)\] once daily for 4 weeks.

Group Type: EXPERIMENTAL

LAMA/LABA

Intervention Type: DRUG

GSK573719/GW642444 inhalation powder used in the Novel Dry Powder Inhaler (DPI): a long-acting beta2-agonist (GSK642444, 25mcg) with a long-acting muscarinic antagonist (GSK573719, 125mcg) combination therapy will be taken once daily for 4 weeks.

LAMA

Intervention Type: DRUG

GSK573719 (125mcg) inhalation powder is a long-acting muscarinic antagonist that will be taken once daily for 4 weeks

LABA/LAMA combination, then LAMA alone

Participants will first receive a long-acting muscarinic antagonist (LAMA) plus long-acting beta2-agonist (LABA) combination product once daily for 4 weeks. After a 2 week washout period, they will then receive the LAMA single product once daily for 4 weeks.

Group Type: EXPERIMENTAL

LAMA/LABA

Intervention Type: DRUG

GSK573719/GW642444 inhalation powder used in the Novel Dry Powder Inhaler (DPI): a long-acting beta2-agonist (GSK642444, 25mcg) with a long-acting muscarinic antagonist (GSK573719, 125mcg) combination therapy will be taken once daily for 4 weeks.

LAMA

Intervention Type: DRUG

GSK573719 (125mcg) inhalation powder is a long-acting muscarinic antagonist that will be taken once daily for 4 weeks

Interventions

LAMA/LABA

GSK573719/GW642444 inhalation powder used in the Novel Dry Powder Inhaler (DPI): a long-acting beta2-agonist (GSK642444, 25mcg) with a long-acting muscarinic antagonist (GSK573719, 125mcg) combination therapy will be taken once daily for 4 weeks.

Intervention Type: DRUG

LAMA

GSK573719 (125mcg) inhalation powder is a long-acting muscarinic antagonist that will be taken once daily for 4 weeks

Intervention Type: DRUG

Other Intervention Names

GSK573719+GW642444; umeclidinium (GSK573719) / vilanterol (GW642444); Anoro ELLIPTA; umeclidinium

Eligibility Criteria

Inclusion Criteria

• Stable moderate COPD
• Post-bronchodilator FEV1/FVC<0.7 and 50%≤FEV1<80% predicted
• Baseline Dyspnea Index ≤ 9 and MRC dyspnea scale >2
• Cigarette smoking history at least 20 pack-years

Exclusion Criteria

• Presence of a significant disease other than COPD that could contribute to dyspnea and exercise limitation
• Important contraindications to clinical exercise testing
• Use of daytime oxygen
• History of asthma

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Queen's University

OTHER

Sponsor Role: lead

Responsible Party

Dr. Denis O'Donnell

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Denis E O'Donnell, MD, FRCPC

Role: PRINCIPAL_INVESTIGATOR

Queen's University and Kingston General Hospital

Locations

Respiratory Investigation Unit at Kingston General Hospital

Kingston, Ontario, Canada

Countries

Canada

Other Identifiers

DMED-1426-11

Identifier Type: -

Identifier Source: org_study_id