Efficacy and Safety Study of QVA149 in COPD Patients

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

A Multi-center, Randomized, Double-blind, Double-dummy, Active Controlled, 2-period Cross-over Study to Assess the Efficacy, Safety and Tolerability of Indacaterol Maleate/Glycopyrronium Bromide Compared to Umeclidinium Bromide/Vilanterol in COPD Patients With Moderate to Severe Airflow Limitation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02487446
• Other study ID #: CQVA149A2349
• Status: Completed
• Phase: Phase 3
• First received: June 29, 2015
• Last updated: November 30, 2017
• Start date: July 28, 2015
• Est. completion date: September 12, 2016

Study information

• Verified date: November 2017
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 357
• Est. completion date: September 12, 2016
• Est. primary completion date: September 12, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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 ß2 agonists

• Other protocol-defined inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• QVA149
QVA149 capsules for inhalation, delivered via QVA149 single dose dry powder inhaler (SDDPI)
• Umeclidinium/vilanterol
Umeclidinium/vilanterol for inhalation, delivered via ELLIPTA® inhaler
• Placebo (umeclidinium/vilanterol)
Matching Placebo to umeclidinium/vilanterol for inhalation, delivered via ELLIPTA® inhaler
• Placebo (QVA149)
Matching Placebo to QVA149 capsules for inhalation, delivered via QVA149 SDDPI

Locations

Country	Name	City	State
United States	Novartis Investigative Site	Altamonte Springs	Florida
United States	Novartis Investigative Site	Andalusia	Alabama
United States	Novartis Investigative Site	Anniston	Alabama
United States	Novartis Investigative Site	Carrollton	Texas
United States	Novartis Investigative Site	Channelview	Texas
United States	Novartis Investigative Site	Charlotte	North Carolina
United States	Novartis Investigative Site	Cincinnati	Ohio
United States	Novartis Investigative Site	Colorado Springs	Colorado
United States	Novartis Investigative Site	Columbia	Maryland
United States	Novartis Investigative Site	Columbus	Ohio
United States	Novartis Investigative Site	Columbus	Ohio
United States	Novartis Investigative Site	Conyers	Georgia
United States	Novartis Investigative Site	Cornelius	North Carolina
United States	Novartis Investigative Site	DeLand	Florida
United States	Novartis Investigative Site	Dublin	Ohio
United States	Novartis Investigative Site	Duluth	Georgia
United States	Novartis Investigative Site	Edina	Minnesota
United States	Novartis Investigative Site	Fayetteville	Arkansas
United States	Novartis Investigative Site	Fort Lauderdale	Florida
United States	Novartis Investigative Site	Fort Worth	Texas
United States	Novartis Investigative Site	Fridley	Minnesota
United States	Novartis Investigative Site	Gastonia	North Carolina
United States	Novartis Investigative Site	Henderson	Nevada
United States	Novartis Investigative Site	Hickory	North Carolina
United States	Novartis Investigative Site	High Point	North Carolina
United States	Novartis Investigative Site	Huntersville	North Carolina
United States	Novartis Investigative Site	Huntington Beach	California
United States	Novartis Investigative Site	Jasper	Alabama
United States	Novartis Investigative Site	Kissimmee	Florida
United States	Novartis Investigative Site	Lampasas	Texas
United States	Novartis Investigative Site	Marion	Ohio
United States	Novartis Investigative Site	McKinney	Texas
United States	Novartis Investigative Site	Medford	Oregon
United States	Novartis Investigative Site	Meridian	Idaho
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Minneapolis	Minnesota
United States	Novartis Investigative Site	Minneapolis	Minnesota
United States	Novartis Investigative Site	Multiple Locations	Alabama
United States	Novartis Investigative Site	Multiple Locations	Arizona
United States	Novartis Investigative Site	New Braunfels	Texas
United States	Novartis Investigative Site	New Orleans	Louisiana
United States	Novartis Investigative Site	New York	New York
United States	Novartis Investigative Site	Newport News	Virginia
United States	Novartis Investigative Site	Pensacola	Florida
United States	Novartis Investigative Site	Pensacola	Florida
United States	Novartis Investigative Site	Philadelphia	Pennsylvania
United States	Novartis Investigative Site	Plymouth	Minnesota
United States	Novartis Investigative Site	Port Orange	Florida
United States	Novartis Investigative Site	Portland	Oregon
United States	Novartis Investigative Site	Rancho Mirage	California
United States	Novartis Investigative Site	Salt Lake City	Utah
United States	Novartis Investigative Site	Slidell	Louisiana
United States	Novartis Investigative Site	Sunset	Louisiana
United States	Novartis Investigative Site	Tacoma	Washington
United States	Novartis Investigative Site	Tempe	Arizona
United States	Novartis Investigative Site	Tipton	Pennsylvania
United States	Novartis Investigative Site	Tucson	Arizona
United States	Novartis Investigative Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Forced Expiratory Volume (FEV1) Area Under the Curve (AUC) 0-24h	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.	baseline, 0 to 24 hours post-dose at week 12
Secondary	Change From Baseline in Forced Expiratory Volume (FEV1) Area Under the Curve (AUC) 0-24h	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.	baseline, 0 to 24 hours post-dose at week 12
Secondary	Change From Baseline in Trough FEV1 (Mean of 23h 15 Minutes and 23 h 45 Minutes Post Previous Morning Dose)	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	baseline, 23 hours 15 minutes and 23 hours 45 minutes post previous morning dose at week 12
Secondary	Change From Baseline in FEV1 AUC 12-24h	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).	baseline, 12 hours to 24 hours post-dose at week 12
Secondary	Change From Baseline in FEV1 AUC 0-12h	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).	baseline, 0 to 12 hours post-dose at week 12
Secondary	Change From Baseline in FEV1 AUC 0-4h, AUC 4-8h, AUC 8-12h, AUC 12-16h, AUC 16-20h and AUC 20-24h	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.	baseline, 12 weeks
Secondary	Change From Baseline in Pre-dose Trough FEV1 (Mean of 15 Minutes and 45 Minutes Pre Morning Dose)	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.	baseline, 15 minutes and 45 minutes pre morning dose at week 12
Secondary	QVA149 Compared to Umeclidinium/Vilanterol in Terms of Change From Baseline in FEV1 at Any Time Point	FEV1 was measured with spirometry conducted according to internationally accepted standards.	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)
Secondary	QVA149 Compared to Umeclidinium/Vilanterol in Terms of Change From Baseline in Forced Vital Capacity (FVC) at Any Time Point	FEV1 was measured with spirometry conducted according to internationally accepted standards.	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)