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

Chronic Obstructive Pulmonary Disease Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01490125
• Other study ID #: CQVA149A2322
• Secondary ID: 2011-000229-63
• Status: Completed
• Phase: Phase 3
• First received: November 15, 2011
• Last updated: November 5, 2013
• Start date: October 2011
• Est. completion date: August 2012

Study information

• Verified date: November 2013
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health ProductsCanada: Ethics Review CommitteeCanada: Health CanadaGermany: Ethics CommissionGermany: Federal Institute for Drugs and Medical DevicesSpain: Ministry of Health and ConsumptionSpain: Comité Ético de Investigación ClínicaSpain: Ethics CommitteeUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 247
• Est. completion date: August 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• QVA149
QVA149 110/50 µg hard non-gelatin capsule, inhalation/blister once a day via SDDPI
• Tiotropium
Tiotropium 18 ug hard gelatin capsule, inhalation/ blister once a day via HandiHaler® device
• Placebo to QVA149
Placebo 0 mg hard non-gelatin capsule, inhalation/ blister once a day via SDDPI
• Placebo to tiotropium
Placebo 0 mg hard gelatin capsule, inhalation/ blister once a day via HandiHaler® device
• Salbutamol/albuterol
salbutamol/albuterol (containing CFC-free propellant -HFA 134a) inhaler used as rescue medication when needed.

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Gilly
Belgium	Novartis Investigative Site	Jambes
Belgium	Novartis Investigative Site	Jette
Belgium	Novartis Investigative Site	Leuven
Belgium	Novartis Investigative Site	Liege
Belgium	Novartis Investigative Site	Oostende
Belgium	Novartis Investigative Site	Wavre
Canada	Novartis Investigative Site	Burlington	Ontario
Canada	Novartis Investigative Site	Laval	Quebec
Canada	Novartis Investigative Site	Mirabel	Quebec
Canada	Novartis Investigative Site	Mississauga	Ontario
Canada	Novartis Investigative Site	St-Charles-Borromée	Quebec
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
Germany	Novartis Investigative Site	Aschaffenburg
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Cottbus	Sachsen
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Halle
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Potsdam
Germany	Novartis Investigative Site	Potsdam
Germany	Novartis Investigative Site	Rheine
Germany	Novartis Investigative Site	Rüdersdorf
Spain	Novartis Investigative Site	Badalona	Barcelona
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Malaga	Andalucia
Spain	Novartis Investigative Site	Mérida	Badajoz
Spain	Novartis Investigative Site	Ponferrada	Leon
United Kingdom	Novartis Investigative Site	Bradford
United Kingdom	Novartis Investigative Site	Glasgow
United Kingdom	Novartis Investigative Site	Newcastle-upon-Tyne
United Kingdom	Novartis Investigative Site	Portsmouth
United Kingdom	Novartis Investigative Site	Salford	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Belgium,  Canada,  Germany,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline and 6 weeks	No
Secondary	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.	Baseline and 6 weeks	No
Secondary	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.	5min-4hr at day 1 and week 6 post-dose	No
Secondary	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.	5min-4hr at day 1 and week 6 post-dose	No
Secondary	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.	Baseline and 6 weeks	No
Secondary	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	Baseline and 6 weeks	No