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

November 15, 2011
November 5, 2013
October 2011
August 2012   (final data collection date for primary outcome measure)
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.
The improvement in TDI (total transient dyspnea index) score after treatment with QVA149 compared to placebo [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
TDI is part of the BDI/TDI questionnaire where the patient will be asked to indicate whether they have improved or deteriorated since their baseline dypsnea index (BDI)
Complete list of historical versions of study NCT01490125 on ClinicalTrials.gov Archive Site
  • 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
  • The improvement in TDI score after treatment with QVA149 compared to tiotropium [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    TDI is part of the BDI/TDI questionnaire where the patient will be asked to indicate whether they have improved or deteriorated since their baseline dypsnea index (BDI)
  • Forced expiratory volume in one secone (FEV1) area under the curve (AUC)(0-4hrs) after 6 weeks treatment with QVA149 compared to placebo and tiotropium [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    The FEV1 will measure the maximum amount of air a patient can blow out of their lungs in 1 second at several time-points from 0-4 hours.
  • Forced vital capacity (FVC) AUC (0-4 hrs) after treatment with QVA149 compared to placebo and tiotropium [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    FVC is the total amount of air that can be exhaled by the patient after a full inhalation. The FVC will be repeated over several time-points from 0-4 hours.
  • Mean change from baseline in Capacity of Daily Living during the Morning (CDLM) Questionnaire [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    The CDLM is a 7 question questionnaire that will be completed by the patient every morning during the study
  • Mean change from baseline in number of puffs of rescue medication [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    The number of puffs of rescue medication taken by the patient will be collected each day during the study
  • Compare improvement in CDLM Questionnaire to FEV1 AUC 0-4 hrs. [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    The results of the CDLM questionnaire will be compared to the results of the FEV1 AUC 0-4 hours
  • Safety and tolerability [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    Safety and tolerability will be evaulated from laboratory tests and ECG results, vital signs and any adverse events
Not Provided
Not Provided
 
The Effect of QVA149 on Patient Reported Dyspnea in Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)
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

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

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Chronic Obstructive Pulmonary Disease
  • Drug: QVA149
    QVA149 110/50 μg hard non-gelatin capsule, inhalation/blister once a day via SDDPI
  • 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: 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.
  • 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.
    Interventions:
    • Drug: QVA149
    • Drug: Placebo to tiotropium
    • Drug: Salbutamol/albuterol
  • 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.
    Interventions:
    • Drug: Tiotropium
    • Drug: Placebo to QVA149
    • Drug: Salbutamol/albuterol
  • 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.
    Interventions:
    • Drug: Placebo to QVA149
    • Drug: Placebo to tiotropium
    • Drug: Salbutamol/albuterol
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
247
August 2012
August 2012   (final data collection date for primary outcome measure)

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.

Both
40 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Germany,   Belgium,   Canada,   United Kingdom,   Spain
 
NCT01490125
CQVA149A2322, 2011-000229-63
No
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP