Efficacy and Safety Study of Indacaterol Maleate/Glycopyrronium Bromide in Chronic Obstructive Pulmonary Disease (COPD) Patients.

Phase 3

Completed

Conditions: Chronic Obstructive Pulmonary Disease

Interventions: Drug: QVA149
Drug: Umeclidinium/vilanterol
Drug: Placebo (QVA149)
Drug: Placebo (umeclidinium/vilanterol )

Registration Number: NCT02487498

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: The purpose of this study is to demonstrate that the efficacy of the combination product QVA149 is similar to the efficacy of the combination product umeclidinium/vilanterol on a pre-specified endpoint of FEV1 AUC0-24h while maintaining an acceptable safety profile.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 355

Inclusion Criteria

Male or female adults aged ≥40 yrs
Smoking history of at least 10 pack years
Diagnosis of stable Chronic Obstructive Pulmonary Disease (COPD) as classified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines, 2015)
Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1)< 80% and ≥ 30% of the predicted normal value and post-bronchodilator FEV1/FVC (forced vital capacity) <70%
Modified Medical Research Council questionnaire grade of 2 or higher

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: CROSSOVER

Arm && Interventions

Group	Intervention	Description
QVA149	QVA149	QVA149 capsules for inhalation, delivered via QVA149 SDDPI
Umeclidinium/vilanterol	Placebo (QVA149)	Umeclidinium/vilanterol for inhalation, delivered via ELLIPTA® inhaler
QVA149	Placebo (umeclidinium/vilanterol )	QVA149 capsules for inhalation, delivered via QVA149 SDDPI
Umeclidinium/vilanterol	Umeclidinium/vilanterol	Umeclidinium/vilanterol for inhalation, delivered via ELLIPTA® inhaler

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Forced Expiratory Volume (FEV1) Area Under the Curve (AUC) 0-24h	baseline, 0 to 24 hours post-dose at week 12	FEV1 was measured with spirometry conducted according to internationally accepted standards. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time over an entire day (AUC 0-24h). A positive change from baseline indicates improvement.

Secondary Outcome Measures

Name	Time	Method
QVA149 Compared to Umeclidinium/Vilanterol in Terms of Change From Baseline in Pre-dose Trough FEV1 (Mean of 15 Minutes and 45 Minutes Pre Morning Dose)	baseline, 12 weeks	FEV1 was measured with spirometry conducted according to internationally accepted standards. Pre-dose trough FEV1 was defined as the average of measurements made 15 minutes and 45 minutes pre morning dose for each treatment.
QVA149 Compared to Umeclidinium/Vilanterol in Terms of Change From Baseline in Forced Vital Capacity (FVC) at Any Time Point	Day 1 (5min, 15min, 30 min, hours 1, 2, 4, 8, 11h 55min, 23h 15min, 23h 45min); week 6 (-45min, -15min); week 12 (-45min, -15min, 5min, 15min, 30min, hours 1, 2, 4, 8, 11h 55min, 12h 5min, 12h 15min, 12h 30min, 13, 14, 16, 20, 23h 15min, 23h 45min)	FEV1 was measured with spirometry conducted according to internationally accepted standards.
Change From Baseline in Forced Expiratory Volume (FEV1) Area Under the Curve (AUC) 0-24h	baseline, 0 to 24 hours post-dose at week 12	FEV1 was measured with spirometry conducted according to internationally accepted standards. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time over an entire day (AUC 0-24h). A positive change from baseline indicates improvement.
Change From Baseline in FEV1 AUC 12-24h	baseline, 12 hours to 24 hours post-dose at week 12	FEV1 was measured with spirometry conducted according to internationally accepted standards. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time over 12 hours (AUC 12-24h).
QVA149 Compared to Umeclidinium/Vilanterol in Terms of Change From Baseline in FEV1 at Any Time Point	Day 1 (5min, 15min, 30min, hours 1, 2, 4, 8, 11h 55min, 23h 15min, 23h 45min); week 6 (-45min, -15min); week 12 (-45min, -15min, 5min, 15min, 30min, hours 1, 2, 4, 8, 11h 55min, 12h 5min, 12h 15min, 12h 30min, 13, 14, 16, 20, 23h 15min, 23h 45min)	FEV1 was measured with spirometry conducted according to internationally accepted standards.
Superiority of QVA149 Compared to Umeclidinium/Vilanterol in Terms of Change From Baseline in Trough FEV1 (Mean of 23h 15 Minutes and 23 h 45 Minutes Post Previous Morning Dose)	baseline, 23 hours 15 minutes and 23 hours 45 minutes post previous morning dose at week 12	FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 15 minutes and 23 hours 45 minutes post-dose for each treatment.
Change From Baseline in FEV1 AUC 0-12h	baseline, 0 to 12 hours post-dose at week 12	FEV1 was measured with spirometry conducted according to internationally accepted standards. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time over 12 hours (AUC 0-12h).
Change From Baseline in FEV1 AUC 0-4h, AUC 4-8h, AUC 8-12h, AUC 12-16h, AUC 16-20h and AUC 20-24h	baseline, 12 weeks	FEV1 was measured with spirometry conducted according to internationally accepted standards. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time over 4 hour intervals FEV1 AUC 0-4h, AUC 4-8h, AUC 8-12h, AUC 12-16h, AUC 16-20h and AUC 20-24h.