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

NCT01491802 | Completed Phase 3 Results DMC

• 1 other identifier: DMED-1426-11
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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

Keywords

COPD; Combination therapy; Anticholinergic; Beta2-agonist; Exercise; Dyspnea; Respiratory mechanics

Outcome Measures

Primary Outcomes (1)

• Exertional Dyspnea Intensity at Isotime Exercise.

  Intensity of dyspnea (defined as breathing discomfort) at a standardized time (isotime) during constant work rate exercise tests as measured by the modified 10-point Borg scale. A rating of 0 represents no dyspnea up to a maximum of 10: a smaller rating is therefore an improvement. Isotime was defined as the highest exercise time in minutes completed in both post-treatment tests.

  4 weeks

Secondary Outcomes (9)

• Exercise Endurance Time

  4 weeks

• Inspiratory Capacity at Rest

  4 weeks

• Ventilation at Isotime Exercise

  4 weeks

• Intensity of "Unpleasantness of Breathing" at Isotime Exercise

  4 weeks

• Inspiratory Capacity at Isotime Exercise

  4 weeks

Study Arms (2)

LAMA alone, then LAMA/LABA combination

EXPERIMENTAL

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.

Drug: LAMA/LABA; Drug: LAMA

LABA/LAMA combination, then LAMA alone

EXPERIMENTAL

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.

Drug: LAMA/LABA; Drug: LAMA

Interventions

LAMA/LABA 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.

Also known as: GSK573719+GW642444, umeclidinium (GSK573719) / vilanterol (GW642444), Anoro ELLIPTA

LABA/LAMA combination, then LAMA alone; LAMA alone, then LAMA/LABA combination

LAMA DRUG

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

Also known as: umeclidinium

LABA/LAMA combination, then LAMA alone; LAMA alone, then LAMA/LABA combination

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Queen's University: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Respiratory Investigation Unit at Kingston General Hospital

Kingston, Ontario, K7L 2V7, Canada

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Motor Activity; Dyspnea

Interventions

GSK573719; vilanterol

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavior; Respiration Disorders; Signs and Symptoms, Respiratory; Signs and Symptoms

Results Point of Contact

• Title: Kathy Webb
• Organization: Queen's University

kw2@queensu.ca

613-549-6666

Study Officials

• Denis E O'Donnell, MD, FRCPC

  Queen's University and Kingston General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 12, 2011
• First Posted: December 14, 2011
• Study Start: January 1, 2012
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: August 15, 2017
• Results First Posted: August 15, 2017

Record last verified: 2017-05

Locations

CA (1)