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

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

A Multi-center, Randomized, Double-blind, Double-dummy, Active Controlled, Two-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: NCT02487498
• Other study ID #: CQVA149A2350
• Status: Completed
• Phase: Phase 3
• First received: June 29, 2015
• Last updated: March 2, 2018
• Start date: July 27, 2015
• Est. completion date: September 6, 2016

Study information

• Verified date: March 2018
• 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: 355
• Est. completion date: September 6, 2016
• Est. primary completion date: September 6, 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 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	Amarillo	Texas
United States	Novartis Investigative Site	Anaheim	California
United States	Novartis Investigative Site	Anderson	South Carolina
United States	Novartis Investigative Site	Boerne	Texas
United States	Novartis Investigative Site	Charleston	South Carolina
United States	Novartis Investigative Site	Charleston	South Carolina
United States	Novartis Investigative Site	Chiefland	Florida
United States	Novartis Investigative Site	Cincinnati	Ohio
United States	Novartis Investigative Site	Cincinnati	Ohio
United States	Novartis Investigative Site	Clearwater	Florida
United States	Novartis Investigative Site	Easley	South Carolina
United States	Novartis Investigative Site	El Paso	Texas
United States	Novartis Investigative Site	Escondido	California
United States	Novartis Investigative Site	Eugene	Oregon
United States	Novartis Investigative Site	Florence	Kentucky
United States	Novartis Investigative Site	Fort Mill	South Carolina
United States	Novartis Investigative Site	Fort Worth	Texas
United States	Novartis Investigative Site	Gaffney	South Carolina
United States	Novartis Investigative Site	Gainesville	Florida
United States	Novartis Investigative Site	Gastonia	North Carolina
United States	Novartis Investigative Site	Greenfield	Wisconsin
United States	Novartis Investigative Site	Greenville	South Carolina
United States	Novartis Investigative Site	Kingwood	Texas
United States	Novartis Investigative Site	Lincoln	Nebraska
United States	Novartis Investigative Site	Livonia	Michigan
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Monroe	North Carolina
United States	Novartis Investigative Site	Mount Pleasant	South Carolina
United States	Novartis Investigative Site	New Bern	North Carolina
United States	Novartis Investigative Site	North Dartmouth	Massachusetts
United States	Novartis Investigative Site	Omaha	Nebraska
United States	Novartis Investigative Site	Owensboro	Kentucky
United States	Novartis Investigative Site	Plano	Texas
United States	Novartis Investigative Site	Pottstown	Pennsylvania
United States	Novartis Investigative Site	Raleigh	North Carolina
United States	Novartis Investigative Site	Richmond	Virginia
United States	Novartis Investigative Site	Riverside	California
United States	Novartis Investigative Site	Rock Hill	South Carolina
United States	Novartis Investigative Site	Saint Charles	Missouri
United States	Novartis Investigative Site	Saint Louis	Missouri
United States	Novartis Investigative Site	San Antonio	Texas
United States	Novartis Investigative Site	San Diego	California
United States	Novartis Investigative Site	San Diego	California
United States	Novartis Investigative Site	San Diego	California
United States	Novartis Investigative Site	Seneca	South Carolina
United States	Novartis Investigative Site	Shelby	North Carolina
United States	Novartis Investigative Site	Simpsonville	South Carolina
United States	Novartis Investigative Site	Skillman	New Jersey
United States	Novartis Investigative Site	Spartanburg	South Carolina
United States	Novartis Investigative Site	Union	South Carolina
United States	Novartis Investigative Site	Wilmington	North Carolina
United States	Novartis Investigative Site	Winter Park	Florida

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	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)	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	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)	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, 12 weeks
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, 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)