QVA vs. Salmeterol/Fluticasone, 52-week Exacerbation Study, FLAME (EFfect of Indacaterol Glycopyronium Vs Fluticasone Salmeterol on COPD Exacerbations)

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 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 12 hours per day
• Patients with any history of asthma
• Patients with an onset of respiratory symptoms, including a COPD diagnosis prior to age 40 years
• Patients with a blood eosinophil count > 600/mm3 at screening
• Patients with allergic rhinitis who use a H1 antagonist or intra-nasal corticosteroids intermittently (treatment with a stable dose or regimen is permitted)
• Patients with concomitant pulmonary disease (e.g. lung fibrosis, sarcoidosis, interstitial lung disease, pulmonary hypertension)
• Patients with clinically significant bronchiectasis
• Patients with a diagnosis of α-1 anti-trypsin deficiency
• Patients with active pulmonary tuberculosis, unless confirmed by imaging to be no longer active
• Patients with pulmonary lobectomy or lung volume reduction surgery or lung transplantation
• Patients participating in or planning to participate in the active phase of a supervised pulmonary rehabilitation program during the study. (Maintenance program is permitted.)
• Patients receiving any medications in the classes listed in the protocol
• Patients receiving any COPD related medications in the classes specified in the protocol must undergo the required washout period prior to screening and follow the adjustment to treatment program
• Use of other investigational drugs/devices (approved or unapproved) at the time of enrollment, or within 30 days or 5 half-lives of screening, whichever is longer
• Patients unable to use an electronic patient diary and EXACT pro diary
• Patients unable to use a dry powder inhaler device, Metered Dose Inhaler (MDI) or a pressurized MDI (rescue medication) or comply with the study regimen.