A 52-week Treatment, Multi-center, Randomized, Double-blind, Double Dummy, Parallel-group, Active Controlled Study to Compare the Effect of QVA149 (Indacaterol Maleate / Glycopyrronium Bromide) With Salmeterol/Fluticasone on the Rate of Exacerbations in Subjects With Moderate to Very Severe COPD. (FLAME).

Novartis Pharmaceuticals1 site in 1 country3,362 target enrollmentJuly 2013

ConditionsChronic Obstructive Pulmonary Disease (COPD)

InterventionsQVA149 Long acting B2 agonist (LABA) and inhaled corticosteroid (ICS)

DrugsQVA149 Long acting B2 agonist (LABA) and inhaled corticosteroid (ICS)

Overview

Phase: Phase 3
Intervention: QVA149
Conditions: Chronic Obstructive Pulmonary Disease (COPD)
Sponsor: Novartis Pharmaceuticals
Enrollment: 3362
Locations: 1
Primary Endpoint: Rate of COPD Exacerbations
Status: Completed
Last Updated: 9 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This study will assess the efficacy, safety and tolerability of QVA149 in patients with moderate to very severe COPD.

Registry

clinicaltrials.gov

Start Date

July 2013

End Date

September 2015

Last Updated

9 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Novartis Pharmaceuticals

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Written informed consent must be obtained before any assessment is performed
•Male or female adults aged ≥40 years
•Patients with stable Chronic Obstructive Pulmonary Disease ( COPD) according to the current GOLD strategy (GOLD 2011)
•Current or ex-smokers who have a smoking history of at least 10 pack years. (Ten pack-years are defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for 20 years)
•Patients with a post-bronchodilator Forced Expiratory Volume in one second (FEV1) ≥25 and \< 60% of the predicted normal value, and post-bronchodilator FEV1/FVC (Forced Vital Capacity) \< 0.70 at day -
•(Post refers to 1 hour after sequential inhalation of 84 µg (or equivalent dose) of ipratropium bromide and 400 µg of salbutamol)
•A documented history of at least 1 COPD exacerbation in the previous 12 months that required treatment with systemic glucocorticosteroids and/or antibiotics
•Patients taking stable COPD medication (at least 60 days) prior to day 28
•Patients with an mMRC grade of at least 2 at day 28

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 hCG (human Chorionic Gonadotropin) laboratory test
•Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential
•Patients with Type I or uncontrolled Type II diabetes
•Patients with a history of long QT syndrome or whose QTc measured at day 28 (Fridericia method) is prolonged (\>450 ms for males and females) and confirmed by a central assessor. These patients should not be re-screened
•Patients who have a clinically significant ECG abnormality prior to randomization. (These patients should not be re-screened)
•Patients who have a clinically significant laboratory abnormality at screening
•Patients who have clinically significant renal, cardiovascular (such as but not limited to unstable ischemic heart disease, NYHA Class III/IV left ventricular failure, myocardial infarction), arrhythmia (see below for patients with atrial fibrillation), neurological, endocrine, immunological, psychiatric, gastrointestinal, hepatic, or hematological abnormalities which could interfere with the assessment of the efficacy and safety of the study treatment
•Patients with paroxysmal (e.g. intermittent) atrial fibrillation are excluded
•Patients with persistent atrial fibrillation as defined by continuous atrial fibrillation for at least 6 months and controlled with a rate control strategy (i.e., selective beta blocker, calcium channel blocker, pacemaker placement, digoxin or ablation therapy) for at least 6 months may be considered for inclusion. In such patients, atrial fibrillation must be present at both pre-randomization visits, with a resting ventricular rate \< 100/min. At screening the atrial fibrillation must be confirmed by central reading
•Patients contraindicated for treatment with, or having a history of reactions/ hypersensitivity to any of the following inhaled drugs, drugs of a similar class or any component thereof: anticholinergic agents, long and short acting beta-2 agonists, sympathomimetic amines, lactose or any of the other excipients of trial medication

Arms & Interventions

QVA149

QVA149 (110/50 μg) once daily

Intervention: QVA149

Long acting B2 agonist (LABA) and inhaled corticosteroid (ICS)

Salmeterol/fluticasone (50/500μg) b.i.d

Intervention: Long acting B2 agonist (LABA) and inhaled corticosteroid (ICS)

Outcomes

Primary Outcomes

Rate of COPD Exacerbations

Time Frame: 52 weeks

COPD exacerbations starting between first dose and one day after last treatment are included. COPD exacerbations that occurred within 7 days of each other are collapsed as one event. Estimates are from a generalized linear model assuming a negative binomial distribution with terms for treatment, baseline total symptom score, baseline COPD exacerbation history (i.e. number of COPD exacerbations during the past 12 months prior to study), smoking status at screening, ICS use at screening, airflow limitation severity, and region. As the offset variable log(exposure time in years) was used.

Secondary Outcomes

Time to First Moderate to Severe COPD Exacerbations Requiring Treatment With Systemic Corticosteroids(52 weeks)
Change From Baseline in Forced Expiratory Volume in 1 Second AUC (0-12h)(Baseline, 52 weeks)
Rate of Moderate to Severe COPD Exacerbations Requiring Treatment With Systemic Corticosteroids(52 weeks)
Rate of Moderate to Severe COPD Exacerbations Requiring Treatment With Antibiotics(52 weeks)
Forced Expiratory Volume in 1 Second(Baseline, 52 weeks)
Change From Baseline in Total St. George's Respiratory Questionnaire Score(Baseline, 52 weeks)
Change From Baseline in the Number of Puffs of Rescue Medication(Baseline, 52 weeks)
Time to First COPD Exacerbation.(52 weeks)
Rate of Moderate to Severe COPD Exacerbations Requiring Hospitalization. COPD Exacerbations Starting Between First Dose and One Day After Last Treatment Are Included.(52 weeks)
Time to First Moderate to Severe COPD Exacerbations Requiring Treatment With Antibiotics(52 weeks)
Time to First Moderate to Severe COPD Exacerbations Requiring Re-hospitalization Within 30 Days(52 weeks)
Rate of Moderate to Severe COPD Exacerbations.(52 weeks)
Time to First Moderate to Severe COPD Exacerbation.(52 weeks.)
Rate of Moderate to Severe COPD Exacerbations Requiring Re-hospitalization Within 30 Days(52 weeks)
Time to First Moderate to Severe COPD Exacerbations Requiring Hospitalization(52 weeks)
Change From Baseline in the Safety of QVA149 ((110/50 μg o.d.) vs Fluticasone/Salmeterol (500/50μg Bid) in Terms of HPA Axis Function, as Determined by Collection of 24-hour Urine Cortisol.(Baseline, 52 Weeks)
Change From Baseline in Forced Vital Capacity(4 Weeks, 12 Weeks, 26 Weeks, 38 Weeks, 52 Weeks)
Number of Patients With Adverse Events, Serious Adverse Events, and Death(52 weeks of treatment + 30 days)