A Multi-centre Randomized Double Blind 52-week Study to Assess the Safety of QVA149 Compared to QAB149 in Patients With COPD Who Have Moderate to Severe Airflow Limitation

Study Overview
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Brief Summary
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This study is to assess the safety and tolerability of two different doses of QVA149 and QAB149 in patients with moderate to severe airflow limitation.

Official Title
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A Multi-centre Randomized Double Blind 52-week Study to Assess the Safety of QVA149 Compared to QAB149 in Patients With COPD Who Have Moderate to Severe Airflow Limitation

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Drug: QVA149
* Drug: QVA149
* Drug: QAB149
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female adults aged ≥40 years Patients with stable COPD according to GOLD strategy (GOLD 2011). Patients with airflow limitation indicated by a post-bronchodilator FEV1 ≥ 30% and <80% of the predicted normal, and a post-bronchodilator FEV1/FVC < 0.70. Current or ex-smokers who have a smoking history of at least 10 pack years. Patients with an mMRC ≥ grade 2 Exclusion Criteria: History of long QT syndrome or prolonged QTc Patients who have had a COPD exacerbation that required treatment with antibiotics and/or systemic corticosteroids and/or hospitalization in the 6 weeks prior to Visit 1. Patients with Type I or uncontrolled Type II diabetes Patients with a history of asthma or have concomitant pulmonary disease Patients with paroxysmal (e.g. intermittent) atrial fibrillation. Only patients with persistent atrial fibrillation and controlled with a rate control strategy for at least six months could be eligible Patients who have clinically significant renal, cardiovascular, neurological, endocrine, immunological, psychiatric, gastrointestinal, hepatic, or hematological abnormalities which could interfere with the assessment of safety 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 dose 1<br>QVA149 27.5/12.5 μg capsules | Drug: QVA149<br>* QVA149 will be supplied in a capsule form in blister packs for use in the Novartis Concept1 SDDPI<br>|
| Experimental: QVA149 dose 2<br>QVA149 27.5/25 μg capsules | Drug: QVA149<br>* QVA149 will be supplied in a capsule form in blister packs for use in the Novartis Concept1 SDDPI<br>|
| Active Comparator: QAB149<br>QAB149 75 μg capsules | Drug: QAB149<br>* QAB149 and matching placebo will be supplied in capsule form in blister packs for use in the Novartis Concept1 SDDPI<br>Drug: Placebo<br>* To mimic QAB149<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Adverse Events, Serious Adverse Events, and Death | The overall rate of adverse events reported from initiation through 30 days post last dose. | 56 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Premature Discontinuation of Treatment | methodTime to premature treatment discontinuation for each treatment group was displayed using a Kaplan-Meier curve. The date of last dose of study medication was considered as the event date and also as the censoring date for those patients who did not discontinue treatment earl | 56 weeks | 
| Change From Baseline in Pre-dose Trough FEV1 | Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 * visit interaction, and visit, treatment * visit interaction. | Day 29, 57,, 85, 141, 197, 253, 309 and 365 | 
| Change From Baseline in 1 Hour Post-dose FEV1 Measurements | Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 * visit interaction, and visit, treatment * visit interaction. | Day 1, 29, 57, 85, 141, 197, 253, 309, and 365 | 
| Change From Baseline in FVC Measurement at All Post-baseline Time Points | Pulmonary function assessments were performed using centralized spirometry according to international standards. | Day1, 29, 57, 85, 141, 197, 253, 309, and 365 | 
| Percentage of Participants Experiencing Moderate or Severe COPD Exacerbation | Percentage of participants experiencing moderate or severe Chronic Obstructive Pulmonary Disease (COPD) | 52 weeks | 
| Change From Baseline in Mean Total Daily Symptom Scores | The participant recorded symptom scores twice daily in the eDiary. The daily clinical symptoms included: cough, wheezing, shortness of breath, sputum volume, sputum color, and night time awakening. The range of scores for each assessment is 0 to 3 where 0 indications No symptom and 3 indicates a Severe symptom. The maximum daytime total score is 27 and the maximum nighttime total score is 27. The total daily symptom score is obtained by adding the scores for the morning and evening symptoms for each day. The maximum possible total daily score is 54. A negative change from baseline indicated improvement. | 52 weeks | 
| Change From Baseline in the Daily Number of Puffs of Rescue Medication Over the 52 Week Period | Participants completed an electronic diary (eDiary) twice daily at the same time in the morning and evening to record the number of puffs of rescue medication taken in the previous 12 hours. | 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, QAB149, QVA149, indacaterol maleate, gylcopyrronium bromide