The Effect of QVA149 on Patient Reported Dyspnea in Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) (BLAZE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01490125
First received: November 15, 2011
Last updated: November 5, 2013
Last verified: November 2013
  Purpose

This study assessed the effect of QVA149 on patient-reported dyspnea in moderate to severe Chronic Obstructive Pulmonary Disease (COPD) patients.


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
Drug: QVA149
Drug: Tiotropium
Drug: Placebo to QVA149
Drug: Placebo to tiotropium
Drug: Salbutamol/albuterol
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Blinded, Double-dummy, Placebo-controlled, 3-period Cross-over Study to Evaluate the Effect of QVA149 on Patient Reported Dyspnea in Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD), Using Tiotropium as an Active Control

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Total Total Transient Dyspnea Index (TDI) Score After 6 Weeks of Treatment QVA149 Compared to Placebo [ Time Frame: Baseline and 6 weeks ] [ Designated as safety issue: No ]
    Total Transient Dyspnea Index (TDI) is part of the BDI/TDI questionnaire where participants indicated whether they improved or deteriorated since their Baseline Dyspnea Index (BDI). The BDI and TDI each had 3 domains: activities, tasks, and effort. BDI domains were rated from 0 (very severe) to 4 (none) and the rates summed for the total BDI score ranging from 0 to 12; the lower the score the worse the severity of dyspnea. TDI domains were rated from -6 (major deterioration) to 6 (major improvement) and the rates summed for the total TDI score ranging from -18 to 18. However, to ensure comparability with the TDI paper version, all TDI values were divided by 2 before the analysis. If data was missing or insufficient for any one of the domains a BDI/TDI was calculated. BDI = Baseline Dyspnea Index taken 75 min prior to the first dose in each treatment period. TDI = Transition Dyspnea Index taken after 6 weeks of treatment 75 min prior to the last dose in each treatment period.


Secondary Outcome Measures:
  • Total Total Transient Dyspnea Index (TDI) Score After 6 Weeks of Treatment QVA149 Compared to Tiotropium [ Time Frame: Baseline and 6 weeks ] [ Designated as safety issue: No ]
    Total Transient Dyspnea Index (TDI) is part of the BDI/TDI questionnaire where participants indicated whether they improved or deteriorated since their Baseline Dyspnea Index (BDI). The BDI and TDI each had 3 domains: activities, tasks, and effort. BDI domains were rated from 0 (very severe) to 4 (none) and the rates summed for the total BDI score ranging from 0 to 12; the lower the score the worse the severity of dyspnea. TDI domains were rated from -6 (major deterioration) to 6 (major improvement) and the rates summed for the total TDI score ranging from -18 to 18. However, to ensure comparability with the TDI paper version, all TDI values were divided by 2 before the analysis. If data was missing or insufficient for any one of the domains a BDI/TDI was calculated. BDI = Baseline Dyspnea Index taken 75 min prior to the first dose in each treatment period. TDI = Transition Dyspnea Index taken after 6 weeks of treatment 75 min prior to the last dose in each treatment period.

  • Standardized Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 5min-4h After First Dose and 6 Weeks of Treatment With QVA149 Compared to Placebo and Tiotropium [ Time Frame: 5min-4hr at day 1 and week 6 post-dose ] [ Designated as safety issue: No ]
    Forced Expiratory Volume in 1 second (FEV1) was measured with spirometry conducted according to internationally accepted standards. Measurements were taken at 5 min- 4hr post-dose of day 1 and week 6. The standardized FEV1 Area under the curve (AUC) was calculated as the sum of trapezoids divided by the length of time.

  • Standardized Forced Vital Capacity (FVC) Area Under the Curve (AUC) 5min-4 Hrs After First Dose and 6 Weeks of Treatment With QVA149 Compared to Placebo and Tiotropium [ Time Frame: 5min-4hr at day 1 and week 6 post-dose ] [ Designated as safety issue: No ]
    Forced Vital Capacity (FVC) is the total amount of air that can be exhaled by the patient after a full inhalation. The FVC was measured via spirometry conducted according to internationally accepted standards at 5 min-4 hr post dose of day 1 and week 6.

  • Change From Baseline in The Capacity of Daily Living During the Morning (CDLM) Score Averaged Over 6 Weeks of Treatment [ Time Frame: Baseline and 6 weeks ] [ Designated as safety issue: No ]
    The Capacity of Daily Living during the Morning (CDLM) is a self-administered daily assessment. The CDLM asks COPD patients to (i) report their ability to carry out 6 morning activities and (ii) rate the difficulty in performing those activities on a five point Likert-type scale ranging from "not at all difficult" to "extremely difficult". For each of the six morning activities a score ranging from 0 (=so difficult that they could not carry out the activity by themselves) to 5 (not at all difficult to carry out the activity by themselves) is calculated by using the responses from the two questions for each activity. Daily CDLM is calculated using the scores average from the 6 morning activities. CDLM is calculated as the average daily CDLM score over 6 weeks of treatment. The change from baseline in CDLM score over 6 weeks is analyzed using a MIXED model with baseline CDLM score as a covariate. A CDLM score of 0.20 is considered to be a minimal clinically important difference.

  • Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication Used Over the 6 Weeks of Treatment [ Time Frame: Baseline and 6 weeks ] [ Designated as safety issue: No ]
    The number of puffs of rescue medication taken by participants, were collected each day during the study via entries in e-diaries


Enrollment: 247
Study Start Date: October 2011
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: QVA149 + placebo to tiotropium
Participants received QVA149 plus placebo to tiotropium during 1 of 3 treatment periods, once a day for 6 weeks. Participants were provided with a salbutamol/albuterol inhaler to use as rescue medication.
Drug: QVA149
QVA149 110/50 μg hard non-gelatin capsule, inhalation/blister once a day via SDDPI
Drug: Placebo to tiotropium
Placebo 0 mg hard gelatin capsule, inhalation/ blister once a day via HandiHaler® device
Drug: Salbutamol/albuterol
salbutamol/albuterol (containing CFC-free propellant -HFA 134a) inhaler used as rescue medication when needed.
Active Comparator: Tiotropium + placebo to QVA149
Participants received tiotropium 18 μg plus placebo to QVA149 during 1 of 3 treatment periods once a day for 6 weeks. Participants were provided with a salbutamol/albuterol inhaler to use as rescue medication.
Drug: Tiotropium
Tiotropium 18 ug hard gelatin capsule, inhalation/ blister once a day via HandiHaler® device
Drug: Placebo to QVA149
Placebo 0 mg hard non-gelatin capsule, inhalation/ blister once a day via SDDPI
Drug: Salbutamol/albuterol
salbutamol/albuterol (containing CFC-free propellant -HFA 134a) inhaler used as rescue medication when needed.
Placebo Comparator: Placebo
Participants received placebo to QVA149 plus placebo to tiotropium during 1 of 3 treatment periods once a day for 6 weeks. Participants were provided with a salbutamol/albuterol inhaler to use as rescue medication.
Drug: Placebo to QVA149
Placebo 0 mg hard non-gelatin capsule, inhalation/ blister once a day via SDDPI
Drug: Placebo to tiotropium
Placebo 0 mg hard gelatin capsule, inhalation/ blister once a day via HandiHaler® device
Drug: Salbutamol/albuterol
salbutamol/albuterol (containing CFC-free propellant -HFA 134a) inhaler used as rescue medication when needed.

Detailed Description:

This study used a multi-center, randomized, blinded, double-dummy placebo controlled, three-period crossover design to assess the effect of once daily QVA149 q.d vs. placebo and tiotropium 18 μg q.d. in terms of patient reported dyspnea as assessed by Baseline Dyspnea Index (BDI)/Transient Dyspnea Index (TDI)(SAC version) in patients with moderate to severe COPD.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with moderate to severe stable chronic obstructive pulmonary disease
  • Smoking history of 10 pack years
  • Post-bronchodilator Forced Expiratory Volume in 1 second (FEV1) between 30 - 80%
  • Patients must be able to use computer mouse and display
  • mMRC grade>2

Exclusion Criteria:

  • Patients with a history of long QT syndrome
  • Patients with Type I or uncontrolled Type II diabetes
  • Patients who have had a COPD exacerbation or respiratory tract infection within 6 weeks prior to screening
  • Patients with any history of asthma
  • Patients with pulmonary lobectomy, lung volume reduction surgery, or lung transplantation
  • Patients with concomitant pulmonary disease
  • Patients requiring long term oxygen therapy (>15 h a day)

Other protocol-defined inclusion/exclusion criteria may apply.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01490125

  Hide Study Locations
Locations
Belgium
Novartis Investigative Site
Bruxelles, Belgium, 1000
Novartis Investigative Site
Gilly, Belgium, 6060
Novartis Investigative Site
Jambes, Belgium, 5100
Novartis Investigative Site
Jette, Belgium, 1090
Novartis Investigative Site
Leuven, Belgium, 3000
Novartis Investigative Site
Liege, Belgium, 4000
Novartis Investigative Site
Oostende, Belgium, 8400
Novartis Investigative Site
Wavre, Belgium, 1301
Canada, Ontario
Novartis Investigative Site
Burlington, Ontario, Canada, L7N 3V2
Novartis Investigative Site
Mississauga, Ontario, Canada, L5M 2V8
Novartis Investigative Site
Toronto, Ontario, Canada, M5G1N8
Novartis Investigative Site
Toronto, Ontario, Canada, M6H 3M2
Canada, Quebec
Novartis Investigative Site
Laval, Quebec, Canada, H7S 2M5
Novartis Investigative Site
Mirabel, Quebec, Canada, J7J 2K8
Novartis Investigative Site
St-Charles-Borromée, Quebec, Canada, J6E 6J2
Germany
Novartis Investigative Site
Cottbus, Sachsen, Germany, 03050
Novartis Investigative Site
Aschaffenburg, Germany, 63739
Novartis Investigative Site
Berlin, Germany, 13156
Novartis Investigative Site
Berlin, Germany, 10789
Novartis Investigative Site
Berlin, Germany, 12203
Novartis Investigative Site
Berlin, Germany, 12099
Novartis Investigative Site
Frankfurt, Germany, 60389
Novartis Investigative Site
Halle, Germany, 06108
Novartis Investigative Site
Hannover, Germany, 30317
Novartis Investigative Site
Leipzig, Germany, 04357
Novartis Investigative Site
Leipzig, Germany, 04103
Novartis Investigative Site
Leipzig, Germany, 04207
Novartis Investigative Site
Leipzig, Germany, 04275
Novartis Investigative Site
Mainz, Germany, D-55101
Novartis Investigative Site
Potsdam, Germany, 14478
Novartis Investigative Site
Potsdam, Germany, 14467
Novartis Investigative Site
Rheine, Germany, 48431
Novartis Investigative Site
Rüdersdorf, Germany, 15562
Spain
Novartis Investigative Site
Malaga, Andalucia, Spain, 29010
Novartis Investigative Site
Mérida, Badajoz, Spain, 06800
Novartis Investigative Site
Badalona, Barcelona, Spain, 08914
Novartis Investigative Site
Ponferrada, Leon, Spain, 24400
Novartis Investigative Site
Madrid, Spain, 28007
United Kingdom
Novartis Investigative Site
Salford, Manchester, United Kingdom, M6 8HD
Novartis Investigative Site
Bradford, United Kingdom, BD9 6RJ
Novartis Investigative Site
Glasgow, United Kingdom, G11 6NT
Novartis Investigative Site
Newcastle-upon-Tyne, United Kingdom, NE7 7DN
Novartis Investigative Site
Portsmouth, United Kingdom, PO6 3AD
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01490125     History of Changes
Other Study ID Numbers: CQVA149A2322, 2011-000229-63
Study First Received: November 15, 2011
Results First Received: August 9, 2013
Last Updated: November 5, 2013
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Canada: Ethics Review Committee
Canada: Health Canada
Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices
Spain: Ministry of Health and Consumption
Spain: Comité Ético de Investigación Clínica
Spain: Ethics Committee
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by Novartis:
COPD
Dyspnea
QVA149
tiotropium

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Dyspnea
Respiratory Tract Diseases
Respiration Disorders
Signs and Symptoms, Respiratory
Signs and Symptoms
Albuterol
Tiotropium
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Tocolytic Agents
Reproductive Control Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Parasympatholytics
Cholinergic Antagonists
Cholinergic Agents

ClinicalTrials.gov processed this record on September 29, 2014