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

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.

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.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: QVA149; Drug: Placebo (umeclidinium/vilanterol ); Drug: Umeclidinium/vilanterol; Drug: Placebo (QVA149)

• Study Type: Interventional
• Enrollment (Actual): 355
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • Novartis Investigative Site
    • Escondido, California, United States, 92025
      • Novartis Investigative Site
    • Riverside, California, United States, 92506
      • Novartis Investigative Site
    • San Diego, California, United States, 92103-8415
      • Novartis Investigative Site
    • San Diego, California, United States, 92120
      • Novartis Investigative Site
    • San Diego, California, United States, 92117
      • Novartis Investigative Site
  • Florida
    • Chiefland, Florida, United States, 32626
      • Novartis Investigative Site
    • Clearwater, Florida, United States, 33765
      • Novartis Investigative Site
    • Gainesville, Florida, United States, 32607
      • Novartis Investigative Site
    • Miami, Florida, United States, 33144
      • Novartis Investigative Site
    • Miami, Florida, United States, 33169
      • Novartis Investigative Site
    • Winter Park, Florida, United States, 32789
      • Novartis Investigative Site
  • Kentucky
    • Florence, Kentucky, United States, 41042
      • Novartis Investigative Site
    • Owensboro, Kentucky, United States, 42303
      • Novartis Investigative Site
  • Massachusetts
    • North Dartmouth, Massachusetts, United States, 02747
      • Novartis Investigative Site
  • Michigan
    • Livonia, Michigan, United States, 48152
      • Novartis Investigative Site
  • Missouri
    • Saint Charles, Missouri, United States, 63301
      • Novartis Investigative Site
    • Saint Louis, Missouri, United States, 63141
      • Novartis Investigative Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Novartis Investigative Site
    • Omaha, Nebraska, United States, 68134
      • Novartis Investigative Site
  • New Jersey
    • Skillman, New Jersey, United States, 08558
      • Novartis Investigative Site
  • North Carolina
    • Gastonia, North Carolina, United States, 28054
      • Novartis Investigative Site
    • Monroe, North Carolina, United States, 28112
      • Novartis Investigative Site
    • New Bern, North Carolina, United States, 28562
      • Novartis Investigative Site
    • Raleigh, North Carolina, United States, 27607
      • Novartis Investigative Site
    • Shelby, North Carolina, United States, 28150
      • Novartis Investigative Site
    • Wilmington, North Carolina, United States, 28401
      • Novartis Investigative Site
  • Ohio
    • Cincinnati, Ohio, United States, 45231
      • Novartis Investigative Site
    • Cincinnati, Ohio, United States, 45245
      • Novartis Investigative Site
  • Oregon
    • Eugene, Oregon, United States, 97404
      • Novartis Investigative Site
  • Pennsylvania
    • Pottstown, Pennsylvania, United States, 19464
      • Novartis Investigative Site
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Novartis Investigative Site
    • Charleston, South Carolina, United States, 29407
      • Novartis Investigative Site
    • Charleston, South Carolina, United States, 29406-7108
      • Novartis Investigative Site
    • Easley, South Carolina, United States, 29640
      • Novartis Investigative Site
    • Fort Mill, South Carolina, United States, 29707
      • Novartis Investigative Site
    • Gaffney, South Carolina, United States, 29340
      • Novartis Investigative Site
    • Greenville, South Carolina, United States, 29615
      • Novartis Investigative Site
    • Mount Pleasant, South Carolina, United States, 29464
      • Novartis Investigative Site
    • Rock Hill, South Carolina, United States, 29732
      • Novartis Investigative Site
    • Seneca, South Carolina, United States, 29678
      • Novartis Investigative Site
    • Simpsonville, South Carolina, United States, 29681
      • Novartis Investigative Site
    • Spartanburg, South Carolina, United States, 29303
      • Novartis Investigative Site
    • Union, South Carolina, United States, 29379
      • Novartis Investigative Site
  • Texas
    • Amarillo, Texas, United States, 79106-4165
      • Novartis Investigative Site
    • Boerne, Texas, United States, 78006
      • Novartis Investigative Site
    • El Paso, Texas, United States, 79903
      • Novartis Investigative Site
    • Fort Worth, Texas, United States, 76104
      • Novartis Investigative Site
    • Kingwood, Texas, United States, 77339
      • Novartis Investigative Site
    • Plano, Texas, United States, 75093
      • Novartis Investigative Site
    • San Antonio, Texas, United States, 78299
      • Novartis Investigative Site
  • Virginia
    • Richmond, Virginia, United States, 23225
      • Novartis Investigative Site
  • Wisconsin
    • Greenfield, Wisconsin, United States, 53228
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: QVA149; QVA149 capsules for inhalation, delivered via QVA149 SDDPI	Drug: QVA149; QVA149 capsules for inhalation, delivered via QVA149 SDDPI; Drug: Placebo (umeclidinium/vilanterol ); Matching Placebo to umeclidinium/vilanterol for inhalation, delivered via ELLIPTA® inhaler
Experimental: Umeclidinium/vilanterol; Umeclidinium/vilanterol for inhalation, delivered via ELLIPTA® inhaler	Drug: Umeclidinium/vilanterol; Umeclidinium/vilanterol for inhalation, delivered via ELLIPTA® inhaler; Drug: Placebo (QVA149); Matching Placebo to QVA149 capsules for inhalation, delivered via QVA149 SDDPI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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)
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)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Kerwin E, Ferguson GT, Sanjar S, Goodin T, Yadao A, Fogel R, Maitra S, Sen B, Ayers T, Banerji D. Dual Bronchodilation with Indacaterol Maleate/Glycopyrronium Bromide Compared with Umeclidinium Bromide/Vilanterol in Patients with Moderate-to-Severe COPD: Results from Two Randomized, Controlled, Cross-over Studies. Lung. 2017 Dec;195(6):739-747. doi: 10.1007/s00408-017-0055-9. Epub 2017 Oct 9.

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2015
• Primary Completion (Actual): September 6, 2016
• Study Completion (Actual): September 6, 2016

Study Registration Dates

• First Submitted: June 29, 2015
• First Submitted That Met QC Criteria: June 29, 2015
• First Posted (Estimate): July 1, 2015

Study Record Updates

• Last Update Posted (Actual): April 2, 2018
• Last Update Submitted That Met QC Criteria: March 2, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Chronic Obstructive Pulmonary Disease (COPD)
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Adjuvants, Anesthesia; Glycopyrrolate
• Other Study ID Numbers: CQVA149A2350

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No