A Multi-centre Randomized Double Blind 52-week Study to Assess the Safety of QVA149 Compared to QAB149 in Patients With COPD Who Have Moderate to Severe Airflow Limitation

This study is to assess the safety and tolerability of two different doses of QVA149 and QAB149 in patients with moderate to severe airflow limitation.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Drug: QVA149; Drug: QAB149; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 614
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Pleven, Bulgaria, 5800
    • Novartis Investigative Site
  • Plovdiv, Bulgaria, 4002
    • Novartis Investigative Site
  • Ruse, Bulgaria, 7002
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1431
    • Novartis Investigative Site
  • Varna, Bulgaria, 9010
    • Novartis Investigative Site
• Finland
  • HUS, Finland, 00029
    • Novartis Investigative Site
  • Helsinki, Finland, 00029
    • Novartis Investigative Site
  • Pori, Finland, FIN-28500
    • Novartis Investigative Site
  • Turku, Finland, 20521
    • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, 1125
    • Novartis Investigative Site
  • Budapest, Hungary, 1046
    • Novartis Investigative Site
  • Gyor, Hungary, 9024
    • Novartis Investigative Site
  • Mako, Hungary, 6900
    • Novartis Investigative Site
  • Nyiregyhaza, Hungary, 4400
    • Novartis Investigative Site
  • Pecs, Hungary, 7635
    • Novartis Investigative Site
  • Szazhalombatta, Hungary, 2440
    • Novartis Investigative Site
  • Szolnok, Hungary, H-5000
    • Novartis Investigative Site
  • Torokbalint, Hungary, 2045
    • Novartis Investigative Site
• Puerto Rico
  • Barceloneta, Puerto Rico, 00617
    • Novartis Investigative Site
  • San Juan, Puerto Rico, 00909
    • Novartis Investigative Site
  • San Juan, Puerto Rico, 00918
    • Novartis Investigative Site
• Romania
  • Brasov, Romania, 500281
    • Novartis Investigative Site
  • Bucharest, Romania, 060011
    • Novartis Investigative Site
  • Bucuresti, Romania, 50554
    • Novartis Investigative Site
  • Cluj-Napoca, Romania, 400371
    • Novartis Investigative Site
  • District 1
    • Bucharest, District 1, Romania, 10457
      • Novartis Investigative Site
    • Bucharest, District 1, Romania, 11475
      • Novartis Investigative Site
  • District 3
    • Bucharest, District 3, Romania, 030303
      • Novartis Investigative Site
    • Bucharest, District 3, Romania, 030317
      • Novartis Investigative Site
  • Jud. Constanta
    • Constanta, Jud. Constanta, Romania, 900002
      • Novartis Investigative Site
  • Jud. Iasi
    • Iasi, Jud. Iasi, Romania, 700115
      • Novartis Investigative Site
• Spain
  • Andalucia
    • Granada, Andalucia, Spain, 18014
      • Novartis Investigative Site
    • Málaga, Andalucia, Spain, 29010
      • Novartis Investigative Site
  • Cataluña
    • Badalona, Cataluña, Spain, 08914
      • Novartis Investigative Site
    • Barcelona, Cataluña, Spain
      • Novartis Investigative Site
    • Canet de Mar, Cataluña, Spain, 08360
      • Novartis Investigative Site
    • Centelles, Cataluña, Spain, 08540
      • Novartis Investigative Site
    • Tarragona, Cataluña, Spain, 43350
      • Novartis Investigative Site
  • Comunidad Valenciana
    • Valencia, Comunidad Valenciana, Spain, 46015
      • Novartis Investigative Site
• United States
  • Alabama
    • Vestavia, Alabama, United States, 35216
      • Novartis Investigative Site
  • California
    • Huntington Beach, California, United States, 92647
      • Novartis Investigative Site
    • Lakewood, California, United States, 90712-151
      • Novartis Investigative Site
    • Los Angeles, California, United States, 90048
      • Novartis Investigative Site
    • Orange, California, United States, 92868
      • Novartis Investigative Site
    • Stockton, California, United States, 95207
      • Novartis Investigative Site
    • Walnut Creek, California, United States, 94598
      • Novartis Investigative Site
  • Colorado
    • Boulder, Colorado, United States, 80304
      • Novartis Investigative Site
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • Novartis Investigative Site
  • Illinois
    • Lombard, Illinois, United States, 60148
      • Novartis Investigative Site
    • O'Fallon, Illinois, United States, 62269
      • Novartis Investigative Site
    • Peoria, Illinois, United States, 61602
      • Novartis Investigative Site
  • Indiana
    • Evansville, Indiana, United States, 47712
      • Novartis Investigative Site
  • Iowa
    • Ames, Iowa, United States, 50010
      • Novartis Investigative Site
    • Iowa City, Iowa, United States, 52240
      • Novartis Investigative Site
    • Waterloo, Iowa, United States, 50702
      • Novartis Investigative Site
  • Kentucky
    • Bowling Green, Kentucky, United States, 42101
      • Novartis Investigative Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • Novartis Investigative Site
    • Slidell, Louisiana, United States, 70458
      • Novartis Investigative Site
  • Maine
    • Bangor, Maine, United States, 04401
      • Novartis Investigative Site
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Novartis Investigative Site
  • Michigan
    • Livonia, Michigan, United States, 48152
      • Novartis Investigative Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Novartis Investigative Site
  • Mississippi
    • Jackson, Mississippi, United States, 39209
      • Novartis Investigative Site
    • Picayune, Mississippi, United States, 39466
      • Novartis Investigative Site
  • Missouri
    • St. Charles, Missouri, United States, 63301
      • Novartis Investigative Site
  • Montana
    • Missoula, Montana, United States, 59804
      • Novartis Investigative Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Novartis Investigative Site
    • Omaha, Nebraska, United States, 68131
      • Novartis Investigative Site
  • Nevada
    • Henderson, Nevada, United States, 89014
      • Novartis Investigative Site
    • Las Vegas, Nevada, United States, 89119
      • Novartis Investigative Site
  • New York
    • Rochester, New York, United States, 14618
      • Novartis Investigative Site
  • Ohio
    • Dayton, Ohio, United States, 45459
      • Novartis Investigative Site
    • Dublin, Ohio, United States, 43016
      • Novartis Investigative Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Novartis Investigative Site
    • Oklahoma City, Oklahoma, United States, 73103
      • Novartis Investigative Site
  • Oregon
    • Eugene, Oregon, United States, 97404
      • Novartis Investigative Site
    • Medford, Oregon, United States, 97504-8741
      • Novartis Investigative Site
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Novartis Investigative Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37912
      • Novartis Investigative Site
  • Texas
    • Corsicana, Texas, United States, 75110
      • Novartis Investigative Site
    • Ft. Worth, Texas, United States, 76104
      • Novartis Investigative Site
    • Lufkin, Texas, United States, 75904
      • Novartis Investigative Site
    • McKinney, Texas, United States, 75069
      • Novartis Investigative Site
  • Virginia
    • Abingdon, Virginia, United States, 24210
      • Novartis Investigative Site
    • Midlothian, Virginia, United States, 23114
      • Novartis Investigative Site
    • Newport News, Virginia, United States, 23606
      • 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 and female adults aged ≥40 years
• Patients with stable COPD according to GOLD strategy (GOLD 2011).
• Patients with airflow limitation indicated by a post-bronchodilator FEV1 ≥ 30% and <80% of the predicted normal, and a post-bronchodilator FEV1/FVC < 0.70.
• Current or ex-smokers who have a smoking history of at least 10 pack years.
• Patients with an mMRC ≥ grade 2

Exclusion Criteria:

• History of long QT syndrome or prolonged QTc
• Patients who have had a COPD exacerbation that required treatment with antibiotics and/or systemic corticosteroids and/or hospitalization in the 6 weeks prior to Visit 1.
• Patients with Type I or uncontrolled Type II diabetes
• Patients with a history of asthma or have concomitant pulmonary disease
• Patients with paroxysmal (e.g. intermittent) atrial fibrillation. Only patients with persistent atrial fibrillation and controlled with a rate control strategy for at least six months could be eligible
• Patients who have clinically significant renal, cardiovascular, neurological, endocrine, immunological, psychiatric, gastrointestinal, hepatic, or hematological abnormalities which could interfere with the assessment of safety
• Other protocol defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: QVA149 dose 1; QVA149 27.5/12.5 μg capsules	Drug: QVA149; QVA149 will be supplied in a capsule form in blister packs for use in the Novartis Concept1 SDDPI
Experimental: QVA149 dose 2; QVA149 27.5/25 μg capsules	Drug: QVA149; QVA149 will be supplied in a capsule form in blister packs for use in the Novartis Concept1 SDDPI
Active Comparator: QAB149; QAB149 75 μg capsules	Drug: QAB149; QAB149 and matching placebo will be supplied in capsule form in blister packs for use in the Novartis Concept1 SDDPI; Drug: Placebo; To mimic QAB149

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Adverse Events, Serious Adverse Events, and Death	The overall rate of adverse events reported from initiation through 30 days post last dose.	56 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Premature Discontinuation of Treatment	methodTime to premature treatment discontinuation for each treatment group was displayed using a Kaplan-Meier curve. The date of last dose of study medication was considered as the event date and also as the censoring date for those patients who did not discontinue treatment earl	56 weeks
Change From Baseline in Pre-dose Trough FEV1	Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 * visit interaction, and visit, treatment * visit interaction.	Day 29, 57,, 85, 141, 197, 253, 309 and 365
Change From Baseline in 1 Hour Post-dose FEV1 Measurements	Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 * visit interaction, and visit, treatment * visit interaction.	Day 1, 29, 57, 85, 141, 197, 253, 309, and 365
Change From Baseline in FVC Measurement at All Post-baseline Time Points	Pulmonary function assessments were performed using centralized spirometry according to international standards.	Day1, 29, 57, 85, 141, 197, 253, 309, and 365
Percentage of Participants Experiencing Moderate or Severe COPD Exacerbation	Percentage of participants experiencing moderate or severe Chronic Obstructive Pulmonary Disease (COPD)	52 weeks
Change From Baseline in Mean Total Daily Symptom Scores	The participant recorded symptom scores twice daily in the eDiary. The daily clinical symptoms included: cough, wheezing, shortness of breath, sputum volume, sputum color, and night time awakening. The range of scores for each assessment is 0 to 3 where 0 indications No symptom and 3 indicates a Severe symptom. The maximum daytime total score is 27 and the maximum nighttime total score is 27. The total daily symptom score is obtained by adding the scores for the morning and evening symptoms for each day. The maximum possible total daily score is 54. A negative change from baseline indicated improvement.	52 weeks
Change From Baseline in the Daily Number of Puffs of Rescue Medication Over the 52 Week Period	Participants completed an electronic diary (eDiary) twice daily at the same time in the morning and evening to record the number of puffs of rescue medication taken in the previous 12 hours.	52 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: September 7, 2012
• First Submitted That Met QC Criteria: September 7, 2012
• First Posted (Estimate): September 11, 2012

Study Record Updates

• Last Update Posted (Estimate): March 30, 2016
• Last Update Submitted That Met QC Criteria: February 29, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: COPD, QAB149, QVA149, indacaterol maleate, gylcopyrronium bromide
• 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: CQVA149A2340; 2012-001998-93