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)

Study Overview
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Brief Summary
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The study assessed 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).

Detailed Description
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The study assessed 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).

Official Title
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A Study to Compare the Efficacy and Safety of Once Daily QVA149 Versus the Once Daily Concurrent Administration of QAB149 Plus NVA237 in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: QVA149
* Drug: NVA237
* Drug: QAB149
* 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, 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
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>QVA149 plus placebo once daily for 28 days. | Drug: QVA149<br>* QVA149 110/50 ug supplied as capsules in blister packs for inhalation via SDDPI, once daily<br>Drug: Placebo<br>* Placebo capsules provided in blister packs for inhalation via SDDPI, once daily<br>|
| Active Comparator: QAB149 + NVA237<br>Indacaterol maleate (QAB149) plus glycopyrronium bromide (NVA237) once daily for 28 days. | Drug: NVA237<br>* NVA237 50 ug supplied as capsules in blister packs for inhalation via SDDPI, once daily<br>Drug: QAB149<br>* QAB149 150 ug supplied as capsules in blister packs for inhalation via SDDPI , once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough Forced Expiratory Volume in 1 Second (FEV1) After 28 Days of Blinded Treatment | Spirometry was conducted according to internationally accepted standards. Trough FEV1 is defined as the average of the 23 hour 15 minute and 23 hour 45 minute post-dose FEV1 readings measured at day 29, after 28 days of treatment. Mixed model: Trough FEV1 = treatment + baseline FEV1 + FEV1 reversibility components + baseline smoking status + baseline ICS use + country + center (country) + error. Center was included as a random effect nested within country. | Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-4 Hours at Day 1 | Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-4h at Day 1 was measured via spirometry conducted according to internationally accepted standards. Measurements were made at 0, 5, 15, and 30 minutes; and 1, 2, 3 and 4 hours post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. Mixed model used: AUC FEV1 = treatment + baseline FEV1 + FEV1 reversibility components + baseline smoking status + baseline ICS use + country + center (country) + error. Center was included as a random effect nested within country. | 0, 5, 15, and 30 minutes; and 1, 2, 3 and 4 hours post-dose at Day 1 | 
| Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-4 Hours at Day 28 | Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-4h at Day 28 was measured via spirometry conducted according to internationally accepted standards. Measurements were made at 0, 5, 15, and 30 minutes; and 1, 2, 3 and 4 hours post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. Mixed model used: AUC FEV1 = treatment + baseline FEV1 + FEV1 reversibility components + baseline smoking status + baseline ICS use + country + center (country) + error. Center was included as a random effect nested within country. | 0, 5, 15, and 30 minutes; and 1, 2, 3 and 4 hours post-dose at Day 28 | 
| Peak Forced Expiratory Volume in 1 Second (FEV1) on Days 1 and 28 Post-dose | Spirometry was conducted according to internationally accepted standards. Peak FEV1 is the maximum FEV1 recorded in the period between 5 minutes and 4 hours post dose. Analysis of Covariance was carried out with a mixed model that used (period) baseline, defined as the value of FEV1 measured prior to the first study drug intake in the period, as a covariate. | 5 min - 4 hr at Days 1 and 28 | 
| Time Course of Forced Expiratory Volume in One Second (FEV1) (Pre-dose to 4 Hours Post Dose) on Day 28 | Time course of Forced Expiratory Volume in 1 second (FEV1) was measured at -45 min, -15 min predose, 5 min, 30 min, 1 hr, 2hr, 3hr and 4 hr post-dose on Day 28. FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. | -45 min, -15 min predose, 5 min, 30 min, 1 hr, 2hr, 3hr and 4 hr post-dose on Day 28 | 
| Change From Baseline in the Mean Daily, (Daytime and Nighttime Combined) Number of Puffs of Rescue Medication Used Over 28 Days of Treatment | The number of puffs of rescue medication taken in the previous 12 hours was recorded in the Patient Diary in the morning and evening. The total number of puffs of rescue medication per day over the whole active treatment period was calculated and divided by the total number of days with non-missing rescue data to derive the mean daily number of puffs of rescue medication taken for the patient. If the number of puffs was missing for part of the day (either morning or evening) then a half day was used in the denominator. | Baseline and 28 days | 
| Change From Baseline in Percentage of Days With 'no Daytime Symptoms' Over 28 Days of Treatment | The mean total symptom scores and mean individual symptom scores for the patient were calculated for the whole study period. The mean change from baseline in the total scores and in the individual scores were summarized by treatment and were analyzed for the percentage of 'nights with no nighttime awakenings'. The symptom variables for the whole active treatment period was analyzed using the similar MIXED model as for the primary endpoint, with the baseline FEV1 term being replaced by the respective baseline symptom variables. | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic obstructive pulmonary disease, COPD, QVA149, QAB149, NVA237, indacaterol, glycopyrronium bromide