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)

Phase 3

Completed

Conditions: Chronic Obstructive Pulmonary Disease

Interventions: Drug: QVA149
Drug: NVA237
Drug: Placebo
Drug: QAB149

Registration Number: NCT01529632

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: 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: 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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 193

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
QVA149	QVA149	QVA149 plus placebo once daily for 28 days.
QVA149	Placebo	QVA149 plus placebo once daily for 28 days.
QAB149 + NVA237	NVA237	Indacaterol maleate (QAB149) plus glycopyrronium bromide (NVA237) once daily for 28 days.
QAB149 + NVA237	QAB149	Indacaterol maleate (QAB149) plus glycopyrronium bromide (NVA237) once daily for 28 days.

Primary Outcome Measures

Name	Time	Method
Trough Forced Expiratory Volume in 1 Second (FEV1) After 28 Days of Blinded Treatment	Day 29	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.

Secondary Outcome Measures

Name	Time	Method
Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-4 Hours at Day 1	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) 0-4h 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.
Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-4 Hours at Day 28	0, 5, 15, and 30 minutes; and 1, 2, 3 and 4 hours post-dose 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.
Peak Forced Expiratory Volume in 1 Second (FEV1) on Days 1 and 28 Post-dose	5 min - 4 hr at Days 1 and 28	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.
Time Course of Forced Expiratory Volume in One Second (FEV1) (Pre-dose to 4 Hours Post Dose) on Day 28	-45 min, -15 min predose, 5 min, 30 min, 1 hr, 2hr, 3hr and 4 hr 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.
Change From Baseline in the Mean Daily, (Daytime and Nighttime Combined) Number of Puffs of Rescue Medication Used Over 28 Days of Treatment	Baseline and 28 days	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.
Change From Baseline in Percentage of Days With 'no Daytime Symptoms' Over 28 Days of Treatment	28 days	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.