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

Primary Purpose

Chronic Obstructive Pulmonary Disease

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
QVA149
Tiotropium
Placebo to QVA149
Placebo to tiotropium
Salbutamol/albuterol
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease focused on measuring COPD, Dyspnea, QVA149, tiotropium

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Placebo Comparator

Arm Label

QVA149 + placebo to tiotropium

Tiotropium + placebo to QVA149

Placebo

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Total Total Transient Dyspnea Index (TDI) Score After 6 Weeks of Treatment QVA149 Compared to Placebo
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
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
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
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
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
The number of puffs of rescue medication taken by participants, were collected each day during the study via entries in e-diaries

Full Information

First Posted
November 15, 2011
Last Updated
November 5, 2013
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01490125
Brief Title
The Effect of QVA149 on Patient Reported Dyspnea in Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)
Acronym
BLAZE
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2013
Overall Recruitment Status
Completed
Study Start Date
October 2011 (undefined)
Primary Completion Date
August 2012 (Actual)
Study Completion Date
August 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Obstructive Pulmonary Disease
Keywords
COPD, Dyspnea, QVA149, tiotropium

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
247 (Actual)

8. Arms, Groups, and Interventions

Arm Title
QVA149 + placebo to tiotropium
Arm Type
Experimental
Arm Description
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.
Arm Title
Tiotropium + placebo to QVA149
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
QVA149
Intervention Description
QVA149 110/50 μg hard non-gelatin capsule, inhalation/blister once a day via SDDPI
Intervention Type
Drug
Intervention Name(s)
Tiotropium
Intervention Description
Tiotropium 18 ug hard gelatin capsule, inhalation/ blister once a day via HandiHaler® device
Intervention Type
Drug
Intervention Name(s)
Placebo to QVA149
Intervention Description
Placebo 0 mg hard non-gelatin capsule, inhalation/ blister once a day via SDDPI
Intervention Type
Drug
Intervention Name(s)
Placebo to tiotropium
Intervention Description
Placebo 0 mg hard gelatin capsule, inhalation/ blister once a day via HandiHaler® device
Intervention Type
Drug
Intervention Name(s)
Salbutamol/albuterol
Intervention Description
salbutamol/albuterol (containing CFC-free propellant -HFA 134a) inhaler used as rescue medication when needed.
Primary Outcome Measure Information:
Title
Total Total Transient Dyspnea Index (TDI) Score After 6 Weeks of Treatment QVA149 Compared to Placebo
Description
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.
Time Frame
Baseline and 6 weeks
Secondary Outcome Measure Information:
Title
Total Total Transient Dyspnea Index (TDI) Score After 6 Weeks of Treatment QVA149 Compared to Tiotropium
Description
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.
Time Frame
Baseline and 6 weeks
Title
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
Description
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.
Time Frame
5min-4hr at day 1 and week 6 post-dose
Title
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
Description
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.
Time Frame
5min-4hr at day 1 and week 6 post-dose
Title
Change From Baseline in The Capacity of Daily Living During the Morning (CDLM) Score Averaged Over 6 Weeks of Treatment
Description
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.
Time Frame
Baseline and 6 weeks
Title
Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication Used Over the 6 Weeks of Treatment
Description
The number of puffs of rescue medication taken by participants, were collected each day during the study via entries in e-diaries
Time Frame
Baseline and 6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Bruxelles
ZIP/Postal Code
1000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Gilly
ZIP/Postal Code
6060
Country
Belgium
Facility Name
Novartis Investigative Site
City
Jambes
ZIP/Postal Code
5100
Country
Belgium
Facility Name
Novartis Investigative Site
City
Jette
ZIP/Postal Code
1090
Country
Belgium
Facility Name
Novartis Investigative Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Liege
ZIP/Postal Code
4000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Oostende
ZIP/Postal Code
8400
Country
Belgium
Facility Name
Novartis Investigative Site
City
Wavre
ZIP/Postal Code
1301
Country
Belgium
Facility Name
Novartis Investigative Site
City
Burlington
State/Province
Ontario
ZIP/Postal Code
L7N 3V2
Country
Canada
Facility Name
Novartis Investigative Site
City
Mississauga
State/Province
Ontario
ZIP/Postal Code
L5M 2V8
Country
Canada
Facility Name
Novartis Investigative Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G1N8
Country
Canada
Facility Name
Novartis Investigative Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M6H 3M2
Country
Canada
Facility Name
Novartis Investigative Site
City
Laval
State/Province
Quebec
ZIP/Postal Code
H7S 2M5
Country
Canada
Facility Name
Novartis Investigative Site
City
Mirabel
State/Province
Quebec
ZIP/Postal Code
J7J 2K8
Country
Canada
Facility Name
Novartis Investigative Site
City
St-Charles-Borromée
State/Province
Quebec
ZIP/Postal Code
J6E 6J2
Country
Canada
Facility Name
Novartis Investigative Site
City
Cottbus
State/Province
Sachsen
ZIP/Postal Code
03050
Country
Germany
Facility Name
Novartis Investigative Site
City
Aschaffenburg
ZIP/Postal Code
63739
Country
Germany
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
10789
Country
Germany
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
12099
Country
Germany
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
12203
Country
Germany
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
13156
Country
Germany
Facility Name
Novartis Investigative Site
City
Frankfurt
ZIP/Postal Code
60389
Country
Germany
Facility Name
Novartis Investigative Site
City
Halle
ZIP/Postal Code
06108
Country
Germany
Facility Name
Novartis Investigative Site
City
Hannover
ZIP/Postal Code
30317
Country
Germany
Facility Name
Novartis Investigative Site
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Novartis Investigative Site
City
Leipzig
ZIP/Postal Code
04207
Country
Germany
Facility Name
Novartis Investigative Site
City
Leipzig
ZIP/Postal Code
04275
Country
Germany
Facility Name
Novartis Investigative Site
City
Leipzig
ZIP/Postal Code
04357
Country
Germany
Facility Name
Novartis Investigative Site
City
Mainz
ZIP/Postal Code
D-55101
Country
Germany
Facility Name
Novartis Investigative Site
City
Potsdam
ZIP/Postal Code
14467
Country
Germany
Facility Name
Novartis Investigative Site
City
Potsdam
ZIP/Postal Code
14478
Country
Germany
Facility Name
Novartis Investigative Site
City
Rheine
ZIP/Postal Code
48431
Country
Germany
Facility Name
Novartis Investigative Site
City
Rüdersdorf
ZIP/Postal Code
15562
Country
Germany
Facility Name
Novartis Investigative Site
City
Malaga
State/Province
Andalucia
ZIP/Postal Code
29010
Country
Spain
Facility Name
Novartis Investigative Site
City
Mérida
State/Province
Badajoz
ZIP/Postal Code
06800
Country
Spain
Facility Name
Novartis Investigative Site
City
Badalona
State/Province
Barcelona
ZIP/Postal Code
08914
Country
Spain
Facility Name
Novartis Investigative Site
City
Ponferrada
State/Province
Leon
ZIP/Postal Code
24400
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Novartis Investigative Site
City
Salford
State/Province
Manchester
ZIP/Postal Code
M6 8HD
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Bradford
ZIP/Postal Code
BD9 6RJ
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Glasgow
ZIP/Postal Code
G11 6NT
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Newcastle-upon-Tyne
ZIP/Postal Code
NE7 7DN
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Portsmouth
ZIP/Postal Code
PO6 3AD
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
24176997
Citation
Mahler DA, Decramer M, D'Urzo A, Worth H, White T, Alagappan VK, Chen H, Gallagher N, Kulich K, Banerji D. Dual bronchodilation with QVA149 reduces patient-reported dyspnoea in COPD: the BLAZE study. Eur Respir J. 2014 Jun;43(6):1599-609. doi: 10.1183/09031936.00124013. Epub 2013 Oct 31.
Results Reference
derived

Learn more about this trial

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

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