A 12-Week Study to Evaluate the 24-Hour Pulmonary Function Profile of Fluticasone Furoate /Vilanterol (FF/VI) Inhalation Powder 100/25mcg Once-Daily Via a Novel Dry Powder Inhaler Compared With Tiotropium Bromide Inhalation Powder 18mcg Delivered Once-Daily Via the HandiHaler in Subjects With Chronic Obstructive Pulmonary Disease (COPD) Who Have or Are at Risk for Co-morbid Cardiovascular Disease
Overview
- Phase
- Phase 3
- Intervention
- fluticasone furoate/vilanterol 100/25mcg
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Sponsor
- GlaxoSmithKline
- Enrollment
- 623
- Locations
- 1
- Primary Endpoint
- Change From Baseline Trough in 24-hour Weighted Mean FEV1 on Treatment Day 84
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the 24-hour spirometry effect (FEV1) of Fluticasone Furoate/Vilanterol Inhalation Powder 100/25mcg once daily compared with tiotropium bromide inhalation powder 18mcg once daily over a 12-week treatment period in subjects with COPD who have or are at risk for co-morbid cardiovascular disease
Detailed Description
This is a randomized, double-blind, double-dummy, multi-center, parallel-group study. Subjects who meet the eligibility criteria at Screening and at the end of a 2-week Run-In Period will enter a 12-week Treatment Period. There will be a 7-day Follow-up Period after the Treatment Period.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed and dated written informed consent
- •Male or females ≥ 40 years of age
- •Females must be post-menopausal or using a highly effective method for avoidance of pregnancy
- •Established clinical history of COPD by ATS/ERS definition
- •Post-albuterol spirometry criteria: FEV1/FVC ratio ≤ 0.70 and FEV1 ≥30 to ≤ 70% of predicted normal (NHANES III)
- •Former or current smoker ≥10 pack years
- •A history of diagnosed cardiovascular disease or a prior cardiovascular event including any of the following:
- •Established (i.e., by clinical signs or imaging studies) coronary artery disease (CAD)
- •Established (i.e., by clinical signs or imaging studies) peripheral vascular (i.e., arterial) disease (PVD)
- •Previous stroke
Exclusion Criteria
- •Current diagnosis of asthma
- •Subjects with other respiratory disorders including α1-antitrypsin deficiency as the underlying cause of COPD, active tuberculosis, lung cancer, bronchiectasis (Note: focal bronchiectasis is not exclusionary), sarcoidosis, pulmonary fibrosis (Note: focal fibrotic pulmonary lesions are not exclusionary), pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases
- •Lung volume reduction surgery within previous 12 months
- •Clinically significant abnormalities not due to COPD by chest X-ray or CT scan
- •Hospitalized for poorly controlled COPD within 12 weeks of Screening
- •Poorly controlled COPD 6 weeks prior to Screening, defined as acute worsening of COPD that is managed by the subject with corticosteroids or antibiotics or that requires treatment prescribed by a physician
- •Lower respiratory infection requiring antibiotics 6 weeks prior to Screening
- •A moderate or severe COPD exacerbation and/or a lower respiratory tract infection (including pnuemonia) during the Run-In Period
- •An abnormal, clinically significant finding in any liver chemistry, biochemical, or haematology tests at Screening (Visit 1) or upon repeat prior to randomization
- •An abnormal, clinically significant ECG finding at Screening (Visit 1) or upon repeat prior to randomization
Arms & Interventions
fluticasone furoate/vilanterol
inhaled corticosteroid (ICS)/long-acting beta2-agonist (LABA)
Intervention: fluticasone furoate/vilanterol 100/25mcg
tiotropium bromide
anticholinergic
Intervention: tiotropium bromide 18mcg
Outcomes
Primary Outcomes
Change From Baseline Trough in 24-hour Weighted Mean FEV1 on Treatment Day 84
Time Frame: Baseline and Day 84
Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcefully exhaled from the lungs in one second. The weighted mean was calculated from the pre-dose FEV1 and post-dose FEV1 measurements at 5, 15, 30 minutes and 1, 2, 4, 6, 8, 12, 13, 14, 16, 20, and 24 hours on Treatment Day 84. Baseline trough FEV1 was the mean of the two assessments made 30 and 5 minutes pre-dose on Treatment Day 1. Change from Baseline (BL) was calculated as the average of the Day 84 values minus the Baseline value. Analysis was performed using an analysis of covariance (ANCOVA) model with covariates of BL FEV1, exacerbation history and reversibility stratum, smoking status at screening, country, and treatment group.
Secondary Outcomes
- Time to Onset on Treatment Day 1(Baseline and Day 1)
- Change From Baseline in Trough FEV1 at Treatment Day 84(Baseline and Day 84)