Efficacy and Safety Study of QVA149 in COPD Patients

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

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

• Study Type: Interventional
• Enrollment (Actual): 357
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Andalusia, Alabama, United States, 36305
      • Novartis Investigative Site
    • Anniston, Alabama, United States, 36207-5710
      • Novartis Investigative Site
    • Jasper, Alabama, United States, 35501
      • Novartis Investigative Site
    • Multiple Locations, Alabama, United States
      • Novartis Investigative Site
  • Arizona
    • Multiple Locations, Arizona, United States
      • Novartis Investigative Site
    • Tempe, Arizona, United States, 85283
      • Novartis Investigative Site
    • Tucson, Arizona, United States, 85723
      • Novartis Investigative Site
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Novartis Investigative Site
  • California
    • Huntington Beach, California, United States, 92647
      • Novartis Investigative Site
    • Rancho Mirage, California, United States, 92270
      • Novartis Investigative Site
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Novartis Investigative Site
  • Florida
    • Altamonte Springs, Florida, United States, 32701
      • Novartis Investigative Site
    • DeLand, Florida, United States, 32720
      • Novartis Investigative Site
    • Fort Lauderdale, Florida, United States, 33316-192
      • Novartis Investigative Site
    • Kissimmee, Florida, United States, 34741
      • Novartis Investigative Site
    • Miami, Florida, United States, 33172
      • Novartis Investigative Site
    • Pensacola, Florida, United States, 32503
      • Novartis Investigative Site
    • Pensacola, Florida, United States, 32504
      • Novartis Investigative Site
    • Port Orange, Florida, United States, 32127
      • Novartis Investigative Site
  • Georgia
    • Conyers, Georgia, United States, 30094
      • Novartis Investigative Site
    • Duluth, Georgia, United States, 30096
      • Novartis Investigative Site
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Novartis Investigative Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70119
      • Novartis Investigative Site
    • Slidell, Louisiana, United States, 70458
      • Novartis Investigative Site
    • Sunset, Louisiana, United States, 70584
      • Novartis Investigative Site
  • Maryland
    • Columbia, Maryland, United States, 21044
      • Novartis Investigative Site
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Novartis Investigative Site
    • Fridley, Minnesota, United States, 55432
      • Novartis Investigative Site
    • Minneapolis, Minnesota, United States, 55402
      • Novartis Investigative Site
    • Minneapolis, Minnesota, United States, 55407
      • Novartis Investigative Site
    • Plymouth, Minnesota, United States, 55441
      • Novartis Investigative Site
  • Nevada
    • Henderson, Nevada, United States, 89014
      • Novartis Investigative Site
  • New York
    • New York, New York, United States, 10016
      • Novartis Investigative Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Novartis Investigative Site
    • Cornelius, North Carolina, United States, 28031
      • Novartis Investigative Site
    • Gastonia, North Carolina, United States, 28054
      • Novartis Investigative Site
    • Hickory, North Carolina, United States, 28602
      • Novartis Investigative Site
    • High Point, North Carolina, United States, 27262
      • Novartis Investigative Site
    • Huntersville, North Carolina, United States, 28078
      • Novartis Investigative Site
    • Winston-Salem, North Carolina, United States, 27103
      • Novartis Investigative Site
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Novartis Investigative Site
    • Columbus, Ohio, United States, 43215
      • Novartis Investigative Site
    • Columbus, Ohio, United States, 43213
      • Novartis Investigative Site
    • Dublin, Ohio, United States, 43016
      • Novartis Investigative Site
    • Marion, Ohio, United States, 43302
      • Novartis Investigative Site
  • Oregon
    • Medford, Oregon, United States, 97504
      • Novartis Investigative Site
    • Portland, Oregon, United States, 97213
      • Novartis Investigative Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19142
      • Novartis Investigative Site
    • Tipton, Pennsylvania, United States, 16684
      • Novartis Investigative Site
  • Texas
    • Carrollton, Texas, United States, 75010
      • Novartis Investigative Site
    • Channelview, Texas, United States, 77530
      • Novartis Investigative Site
    • Fort Worth, Texas, United States, 76109
      • Novartis Investigative Site
    • Lampasas, Texas, United States, 76550
      • Novartis Investigative Site
    • McKinney, Texas, United States, 75069
      • Novartis Investigative Site
    • New Braunfels, Texas, United States, 78130
      • Novartis Investigative Site
  • Utah
    • Salt Lake City, Utah, United States, 84102
      • Novartis Investigative Site
  • Virginia
    • Newport News, Virginia, United States, 23606
      • Novartis Investigative Site
  • Washington
    • Tacoma, Washington, United States, 98405
      • 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: First QVA149, then Umeclidinium/vilanterol; Participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks. Then after 3 weeks washout, participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation once daily for 12 weeks.	Drug: Umeclidinium/vilanterol; Umeclidinium/vilanterol for inhalation, delivered via ELLIPTA® inhaler; Other Names: ELLIPTA®; Drug: Placebo (QVA149); Matching Placebo to QVA149 capsules for inhalation, delivered via QVA149 SDDPI; Drug: QVA149; QVA149 capsules for inhalation, delivered via QVA149 single dose dry powder inhaler (SDDPI); Other Names: Indecaterol maleate/glycopyrronium bromide; Drug: Placebo (umeclidinium/vilanterol); Matching Placebo to umeclidinium/vilanterol for inhalation, delivered via ELLIPTA® inhaler
Experimental: First Umeclidinium/vilanterol, then QVA149; Participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation once daily for 12 weeks. Then after 3 weeks washout, participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks.	Drug: Umeclidinium/vilanterol; Umeclidinium/vilanterol for inhalation, delivered via ELLIPTA® inhaler; Other Names: ELLIPTA®; Drug: Placebo (QVA149); Matching Placebo to QVA149 capsules for inhalation, delivered via QVA149 SDDPI; Drug: QVA149; QVA149 capsules for inhalation, delivered via QVA149 single dose dry powder inhaler (SDDPI); Other Names: Indecaterol maleate/glycopyrronium bromide; Drug: Placebo (umeclidinium/vilanterol); Matching Placebo to umeclidinium/vilanterol for inhalation, delivered via ELLIPTA® inhaler

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
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 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)
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 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
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)

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 28, 2015
• Primary Completion (Actual): September 12, 2016
• Study Completion (Actual): September 12, 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): December 26, 2017
• Last Update Submitted That Met QC Criteria: November 30, 2017
• Last Verified: November 1, 2017

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; Anticonvulsants; Glycopyrrolate; Bromides
• Other Study ID Numbers: CQVA149A2349

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

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