Comparison of Safety and Efficacy of the Combination Product QVA149A Against the Concurrent Administration of the Individual Components, QAB149 and NVA237, in Patients With Chronic Obstructive Pulmonary Disease (COPD) (BEACON)

• Change From Baseline in the Mean Number of Puffs Per Day of Rescue Medication Over the Study Duration (Baseline to Day 28) [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  Patients will record the number of puffs of rescue medication in the past 12 hours each morning and evening in the diary. The number of puffs per day during active treatment will be calculated and divided by the total number of days with non-missing data to derive the mean daily number of puffs. If the number of puffs is missing for part of the day then a half day will be used in the denominator. Rescue med use during run-in will be used as baseline. The mean change from baseline will be analyzed using the same MIXED model as primary analysis with baseline daily rescue use replacing FEV1.
• Change From Baseline in the Mean Number of Puffs of Rescue Medication During the Daytime and Nighttime Over the Study Duration (Baseline to Day 28) [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  The daytime and nighttime rescue medication use in terms of number of puffs will be calculated in a similar way as for the daily rescue medication use. Change from baseline in the mean daytime and nighttime number of puffs of rescue medication will be analyzed as for the change from baseline in the mean daily number of puffs of rescue medication.
• Percentage of Days With No Puffs of Rescue Medication During the Daytime and Nighttime Over the Study Duration (Baseline to Day 28) [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  A 'day with no rescue use' is defined from diary data as any day where the patient has taken no puffs of rescue medication. The percentage of 'days with no rescue use' will be derived and analyzed as for the percentage of 'nights with no nighttime awakenings'.
• Percentage of Nights With no Nighttime Awakenings Over the 28 Day Treatment Period [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  A night with 'no nighttime awakenings' is defined from diary data as any night where the patient did not wake up due to symptoms. The total number of nights with 'no nighttime awakenings' over the whole treatment period will be divided by the total number of nights where diary recordings have been made in order to derive the percentage nights with 'no nighttime awakenings'.
• Percentage of Days With no Daytime Symptoms Over the 28 Day Treatment Period [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  A day with 'no daytime symptoms' is defined from the diary data as any day where the patient has recorded in the evening no cough, no wheeze, no production of sputum and no feeling of breathlessness (other than when running) and no puffs of rescue medication during the past 12 hours. However, a patient will not be considered symptom free if they have used rescue medication that day even if his/her total daytime symptoms score is zero. The percentage of days with 'no daytime symptoms' will be derived and analyzed as for the percentage of 'nights with no nighttime awakenings'.
• Percentage of Days Able to Perform Usual Daily Activities Over the 28 Day Treatment Period [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  A 'day able to perform usual daily activities' is defined from diary data as any day where the patient was not prevented from performing their usual daily activities due to respiratory symptoms. The percentage of 'days able to perform usual daily activities' will be derived and analyzed as for the percentage of 'nights with no nighttime awakenings'.
• Mean Daily Total Symptom Score Over the 28 Day Treatment Period [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  The mean total symptom scores and mean individual symptom scores for the patient will be calculated for the whole study period. Total score is based on diary entry with total daily score range of 0-54, with 54 being the maximum symptom score. The mean change from baseline in the total scores and in the individual scores will be summarized by treatment and will be analyzed as for the percentage of 'nights with no nighttime awakenings'.
• Number of Participants With Adverse Events, Death, and Serious or Clinically Significant Adverse Events or Related Discontinuations [ Time Frame: 28 days and 30 day follow-up period ] [ Designated as safety issue: Yes ]
  Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
• Safety and tolerability [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

  Data from the ECGs will be summarized by treatment at all time. Vital signs (blood pressure and radial pulse rate) data will be summarized by treatment at 35 min pre-dose and 1 h post-dose time points at Visit 2, 3, and 5.

  All lab data will be listed with abnormal values flagged. The lab values and the change from baseline for continuous lab parameters will be summarized at each visit. A frequency table of results for categorical lab parameters will be produced by visit. Shift tables relative to normal ranges will be used to summarize the change from baseline to post-baseline by visit.

• FEV1 AUC 0-4h at Day 1 and Day 28 [ Time Frame: Day 1 and Day 28 ] [ Designated as safety issue: No ]
  Spirometry will be conducted according to internationally accepted standards. FEV1 was measured at 45 and 15 minutes pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h, 4 h, and at 23 h 15 min and 23 h 45 min post dose, by visit. The mixed model will contain treatment as a fixed effect with the baseline measurement of trough FEV1, FEV1 prior to inhalation of short acting bronchodilator, FEV1 post inhalation of short acting bronchodilator as covariates. This model will also include smoking status at baseline (current/ex-smoker), history of ICS use as fixed effects and center as a random effect.

The study will assess the safety and efficacy of the fixed combination product QVA149 versus the component products QAB149 and NVA237, administered concurrently, in patients that have moderate to severe chronic obstructive pulmonary disease (COPD).

• Drug: QVA149
  QVA149 110/50 ug will be supplied as capsules in blister packs
• Drug: NVA237
  NVA237 50 ug will be supplied as capsules in blister packs
• Drug: QAB149
  QAB149 150 ug will be supplied as capsules in blister packs
• Drug: Placebo
  Placebo capsules will match the appearance of NVA/QAB capsules and be provided in blister packs

• Experimental: QVA149
  QVA149 110/50µg plus placebo once daily delivered via the single dose dry powder inhaler (SDDPI) for 28 days.
  Interventions:

  • Drug: QVA149
  • Drug: Placebo
• Active Comparator: indacaterol (QAB149) plus glycopyrronium bromide (NVA237)
  Indacaterol (QAB149) 150µg plus glycopyrronium bromide (NVA237) 50µg once daily delivered via the single dose dry powder inhaler (SDDPI) for 28 days.
  Interventions:

  • Drug: NVA237
  • Drug: QAB149

Inclusion Criteria:

• Male or female adults aged ≥ 40 yrs
• Smoking history of at least 10 pack years
• Diagnosis of COPD (moderate to severe as classified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines, 2010)
• Post-bronchodilator FEV1 < 80% and ≥ 30% of the predicted normal value and post-bronchodilator FEV1/FVC (forced vital capacity) < 70%

Exclusion Criteria:

• Patients who have had a respiratory tract infection within 4 weeks prior to Visit 1
• Patients with concomitant pulmonary disease
• Patients with a history of asthma
• Any patient with lung cancer or a history of lung cancer
• Patients with a history of certain cardiovascular co-morbid conditions
• Patients with a known history and diagnosis of alpha-1 antitrypsin deficiency
• Patients in the active phase of a supervised pulmonary rehabilitation program
• Patients contraindicated for inhaled anticholinergic agents and β2 agonists

Other protocol-defined inclusion/exclusion criteria may apply