A 26-week Treatment Randomized, Double-blind, Double Dummy, Parallel-group Study to Assess the Efficacy and Safety of QVA149 (Indacaterol / Glycopyrronium Bromide) Compared to Fluticasone/Salmeterol in Patients With Moderate to Severe COPD
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 744
- Locations
- 1
- Primary Endpoint
- Trough Forced Expiratory Volume in One Second (FEV1) Following 26 Weeks of Treatment to Demonstrate the Non-inferiority of QVA149 110/50 μg o.d. to Fluticasone/Salmeterol 500/50 μg b.i.d
Study Overview
Brief Summary
To demonstrate the non-inferiority of QVA149 110/50 µg o.d. to fluticasone/salmeterol 500/50 µg b.i.d. in terms of trough Forced Expiratory Volume in one second (FEV1) (mean of 23 hours 15 min and 23 hours 45 min post QVA149 dose) following 26 weeks of treatment in patients with moderate to severe COPD
Detailed Description
To demonstrate the non-inferiority of QVA149 110/50 µg o.d. to fluticasone/salmeterol 500/50 µg b.i.d. in terms of trough Forced Expiratory Volume in one second (FEV1) (mean of 23 hours 15 min and 23 hours 45 min post QVA149 dose) following 26 weeks of treatment in patients with moderate to severe COPD.
The study population will consist of approximate 736 male and female adults (age 40 years and greater) with a clinical diagnosis of stable COPD [GOLD (2010)] and a smoking history of at least 10 pack years. It is anticipated that approximately 981 patients will need to be screened in order to randomize 736 patients into 2 treatment arms of the study with an equal randomization ratio, meaning QVA149 (368 patients), fluticasone/salmeterol (368 patients). Treatment randomization will be stratified by current/ex-smoker status and prior ICS use. It is intended that 552 patients will complete the study at Week 26 without major protocol deviations. Dropouts will not be replaced.
This will be a multi-national study, including China, and at least two other countries.
Standardization FEV1 AUC0-12h will be performed in a subgroup of around 100 patients (50 patients per treatment arm) in pre-selected centers.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 40 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients with moderate to severe stable COPD (Stage II or Stage III) according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guideline.
- •Current or ex-smokers who have a smoking history of at least 10 pack years. Patients with a post-bronchodilator Forced Expiratory Volume in one second (FEV1) ≥ 30% and < 80% of the predicted normal, and post-bronchodilator FEV1/FVC < 0.
- •Modified Medical Research Council (mMRC) grade of at least 2 at Visit 2.
Exclusion Criteria
- •Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive Human Chorionic Gonadotropin (hCG) laboratory test.
- •Patents with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia (BPH), bladder-neck obstruction, moderate to severe renal impairment or urinary retention. BPH patients who are stable on treatment can be considered.
- •Patients with a history of long QT syndrome or whose QTc measured at run-in (Visit 2) (Fridericia method) is prolonged (>450 ms for males and females) as confirmed by the central Electrocardiogram (ECG) assessor.
- •Patients with Type I or uncontrolled Type II diabetes. Patients who have not achieved spirometry result at Visit 2 in accordance with American Thoracic Society/European Respiratory Society (ATS/ERS) criteria for acceptability and repeatability.
- •Patients with, a) any history of asthma or, b) onset of respiratory symptoms prior to age 40 years.
- •Patients with concomitant pulmonary disease (e.g. lung fibrosis, primary bronchiectasis, sarcoidosis, interstitial lung disorder, pulmonary hypertension).
- •Other protocol-defined inclusion/exclusion criteria may apply
Arms & Interventions
QVA149
QVA149 110/50 µg o.d., delivered via a single-dose dry powder inhaler (SDDPI), consisting of a fixed dose combination of indacaterol 110µg and NVA237 50µg
Intervention: QVA149 (Drug)
QVA149
QVA149 110/50 µg o.d., delivered via a single-dose dry powder inhaler (SDDPI), consisting of a fixed dose combination of indacaterol 110µg and NVA237 50µg
Intervention: Placebo to fluticasone/salmeterol (Drug)
fluticasone/salmeterol
Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device
Intervention: Fluticasone/salmeterol (Drug)
fluticasone/salmeterol
Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device
Intervention: Placebo to QVA149 (Drug)
Outcomes
Primary Outcomes
Trough Forced Expiratory Volume in One Second (FEV1) Following 26 Weeks of Treatment to Demonstrate the Non-inferiority of QVA149 110/50 μg o.d. to Fluticasone/Salmeterol 500/50 μg b.i.d
Time Frame: 26 weeks
Measurement of QVA149 110/50 μg o.d. to fluticasone/salmeterol 500/50 μg b.i.d. in terms of trough FEV1 (mean of 23 h 15 min and 23 h 45 min post QVA149 dose) following 26 weeks of treatment in patients with moderate to severe COPD.
Secondary Outcomes
- Trough Forced Expiratory Volume in One Second (FEV1) Following 26 Weeks of Treatment to Demonstrate the Superiority of QVA 110/50μg o.d. to Fluticasone/Salmeterol 500/50 μg b.i.d(26 weeks)
- Standardized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-4 Hours(Day 1, 12 and 26 weeks)
- Analysis of FEV1 (L) Trough Response (Pre-dose) Over the Whole Treatment Period(6,12,18 and 26 weeks)
- Analysis of Trough FVC (L) Over the Whole Treatment Period(12 and 26 weeks)
- Health Related Quality of Life Analysis of SGRQ Total Score After 26 Weeks of Treatment(26 weeks)
- Analysis of the TDI Focal Score Over the Whole Treatment Period(12 and 26 weeks)
- Rescue Medication Use: Summary of the Mean Daily, Daytime and Nighttime Number of Puffs of Rescue Medication, by 4 Weekly Intervals(12 and 26 weeks)
- Symptoms Reported Using E-diary Over 12 and 26 Weeks of Treatment(26 weeks)