A Study to Assess the Long-term Safety of QVA149

Study Overview
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Brief Summary
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The study is designed to provide long-term safety data for QVA149 in patients with moderate to severe chronic obstructive pulmonary disease (COPD).

Official Title
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A Multicener, Randomised, Double-blind, Placebo-controlled Study, to Assess the Long Term Safety of 52 Weeks Treatment With QVA149 (110 ug Indacaterol/50ug Glycopyrrolate) in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: QVA149
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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, 2008) 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

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: QVA149<br>110µg/50µg capsule for oral inhalation, once daily, delivered by a single dose dry powder inhaler (SDDPI) | Drug: QVA149<br>* capsules for inhalation, delivered by an SDDPI<br>|
| Placebo Comparator: Placebo<br>Placebo to match QVA149, capsules for inhalation once daily, delivered by an SDDPI | Drug: Placebo<br>* capsules for inhalation, delivered by an SDDPI<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events, Serious Adverse Events or Death | Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal lab 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 judgments of the investigators represent significant hazards. | 52 weeks + Follow-up (Up to Day 394) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pre-dose FEV1 | Pre-dose FEV1 is defined as the average of the FEV1 15 minutes pre-dose and FEV1 45 minutes pre-dose. A mixed model was used with treatment as a fixed effect, average of 15 min and 45 min pre-dose FEV1 at visit 3 as the baseline measurement, and FEV1 prior to inhalation and FEV1 60 min post inhalation of two short acting bronchodialators as covariates. The model also included smoking status at baseline, history of ICS use and country as fixed effects with center nested within country as a random effect. | 52 weeks | 
| Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period | Clinically notable hematology values were: hemoglobin - male <115g/L, female <95 g/L; hematocrit - male <0.37v/v, female <0.32v/v; white cell count - <2.8 10E9/L or >16.0 10E9/L; platelets - <75 10E9/L or >700 10E9/L | 52 weeks | 
| Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period | Clinically notable biochemistry values were: sodium <125mmol/L or >160mmol/L; potassium <3.0mmol/L or >6.0mmol/L; BUN >9.99mmol/L; creatinine >176.8µmol/L; total protein (serum) <40g/L or >95g/L; albumin <25g/L; bilirubin (total) >34.2µmol/L; SGPT >3 x ULN; SGOT > 3 x ULN; gamma glutamyltransferase >3 x ULN; alkaline phosphatase (serum) >3 x ULN; glucose <2.78mmol/L or >9.99mmol/L | 52 weeks | 
| Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Timepoint Over the Whole Treatment Period | 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. | 52 weeks | 
| Number of Patients With Notable Change From Baseline in Fridericia's QTc Values at Any Timepoint Over the Whole Treatment Period | Clinically notable change from baseline was and increase from baseline of 30 or greater milliseconds (ms). | 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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QVA149, COPD, combination bronchodilator