Long Term Safety and Tolerability of QVA149 Versus Tiotropium in Japanese Patients With Chronic Obstructive Pulmonary Disease (COPD)

• Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
  Clinically notable hematology values were: hemoglobin - male <11.5g/dL, female <9.5 g/dL; hematocrit - male <37%, female <32%; white cell count - <2800µL or >16000µL; platelets - <7.5 10*4/µL or >70.0 10*4/µL
• Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
  Clinically notable biochemistry values were: total protein - <4.0 g/dL or >9.5 g/dL; albumin <2.5 g/dL; bilirubin (total) >1.9 mg/dL; BUN >27 mg/dL; creatinine >1.99 mg/dL; AST >3 x ULN U/L; ALT >3 x ULN U/L; ALP >3 x ULN U/L; y-GTP >3 x ULN U/L; sodium <125 mEq/L or >160 mEq/L; potassium <3.0 mEq/L or >6.0 mEq/L; glucose <51.0 mg/dL or >180.0 mg/dL
• Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Time-point Over the Whole Treatment Period [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
  Clinically notable vital sign values were: pulse rate - low, <40 bpm or <=50 bpm and decrease from baseline >=15bpm; pulse rate high, >130 bpm or >=120bpm and increase from baseline >=15 bpm. Systolic blood pressure - low, <75 mmHg or <=90 mmHg and decrease from baseline >=20 mmHg; high, >200 mmHg or >=180 mmHg and increase from baseline >=20 mmHg. Diastolic blood pressure - low, <40 mmHg or <=50 mmHg and decrease from baseline >=15 mmHg; high, >115 mmHg or >=105 mmHg and increase from baseline >=15 mmHg.
• Number of Patients With Newly Occurring or Worsening Clinically Notable Fridericia's QTc Values at Any Time-point Over the Whole Treatment Period [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
  Clinically notable change from baseline was an increase from baseline of 30 or greater milliseconds (ms).
• Change in Pre-dose Forced Expiratory Volume in One Second (FEV1) From Baseline [ Time Frame: Weeks 3, 6, 12, 24, 36, 52 ] [ Designated as safety issue: No ]
  Pre-dose FEV1 is defined as the average of the measurements at 45 and 15 min pre-dose. Baseline is defined as the pre-dose FEV1 value on Day 1 (Week 1).
• Change in Pre-dose Forced Vital Capacity (FVC) From Baseline [ Time Frame: Weeks 3, 6, 12, 24, 36, 52 ] [ Designated as safety issue: No ]
  Pre-dose FVC is defined as the average of the measurements at 45 and 15 min pre-dose. Baseline is defined as the pre-dose FVC value on Day 1 (Week 1).

• Safety of QVA149 as compared with tiotropium with regard to vital signs, electrocardiogram (ECG), and laboratory measurements [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
  vital signs (blood pressure, pulse rate), ECG, laboratory measurements (hematology, urinalysis, clinical chemistry)
• To assess the safety of QVA149 as compared with tiotropium with regard to study drug discontinuation [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
  Measure: study drug discontinuation

• Drug: QVA149
  QVA149 (110 μg indacaterol / 50 μg glycopyrronium o.d.), delivered via Concept1
• Drug: Tiotropium
  Tiotropium (18 μg o.d.), delivered via Handihaler®

• Experimental: QVA149
  QVA149 110/50 μg once a day (o.d)
  Intervention: Drug: QVA149
• Active Comparator: Tiotropium
  tiotropium 18 μg o.d.
  Intervention: Drug: Tiotropium

Inclusion Criteria:

• Patients with moderate to severe stable COPD (Stage II or Stage III) according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines 2008.
• 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 etc.)
• Patients with post-bronchodilator forced expiratory volume in one second (FEV1) ≥30% and < 80% of the predicted normal, and post-bronchodilator FEV1/forced vital capacity (FVC) < 0.7 at Visit 2.

Exclusion Criteria:

• Pregnant women or nursing mothers or women of child-bearing potential not using an acceptable method of contraception
• Patients requiring long term oxygen therapy
• Patients who have had a lower respiratory tract infection within 4 weeks prior to Visit 1
• Patients with concomitant pulmonary disease
• Patients with a history of asthma
• Any patient with history of malignancy of any organ system (including lung cancer), treated or untreated, within the past 5 years
• Patients with a history of certain cardiovascular comorbid 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 treatment with, or having a history of reactions/ hypersensitivity to anticholinergic agents, long and short acting beta-2 agonists, sympathomimetic amines

Other protocol-defined inclusion/exclusion criteria may apply