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

NCT01490125 | Completed Phase 3 Results

• 2 other identifiers: CQVA149A23222011-000229-63
• Study Type: interventional
• Target: 247
• Locations: 5 countries
• Sites: 43

Brief Summary

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

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

COPD; Dyspnea; QVA149; tiotropium

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (5)

• Total Total Transient Dyspnea Index (TDI) Score After 6 Weeks of Treatment QVA149 Compared to Tiotropium

  Baseline and 6 weeks

• 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

  5min-4hr at day 1 and week 6 post-dose

• 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

  5min-4hr at day 1 and week 6 post-dose

• Change From Baseline in The Capacity of Daily Living During the Morning (CDLM) Score Averaged Over 6 Weeks of Treatment

  Baseline and 6 weeks

• Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication Used Over the 6 Weeks of Treatment

  Baseline and 6 weeks

Study Arms (3)

QVA149 + placebo to tiotropium

EXPERIMENTAL

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; Drug: Placebo to tiotropium; Drug: Salbutamol/albuterol

Tiotropium + placebo to QVA149

ACTIVE COMPARATOR

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; Drug: Placebo to QVA149; Drug: Salbutamol/albuterol

Placebo

PLACEBO COMPARATOR

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; Drug: Placebo to tiotropium; Drug: Salbutamol/albuterol

Interventions

QVA149 DRUG

QVA149 110/50 μg hard non-gelatin capsule, inhalation/blister once a day via SDDPI

QVA149 + placebo to tiotropium

Tiotropium DRUG

Tiotropium 18 ug hard gelatin capsule, inhalation/ blister once a day via HandiHaler® device

Tiotropium + placebo to QVA149

Placebo to QVA149 DRUG

Placebo 0 mg hard non-gelatin capsule, inhalation/ blister once a day via SDDPI

Placebo; Tiotropium + placebo to QVA149

Placebo to tiotropium DRUG

Placebo 0 mg hard gelatin capsule, inhalation/ blister once a day via HandiHaler® device

Placebo; QVA149 + placebo to tiotropium

Salbutamol/albuterol DRUG

salbutamol/albuterol (containing CFC-free propellant -HFA 134a) inhaler used as rescue medication when needed.

Placebo; QVA149 + placebo to tiotropium; Tiotropium + placebo to QVA149

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (43)

Novartis Investigative Site

Brussels, 1000, Belgium

Location

Novartis Investigative Site

Gilly, 6060, Belgium

Location

Novartis Investigative Site

Jambes, 5100, Belgium

Location

Novartis Investigative Site

Jette, 1090, Belgium

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Liège, 4000, Belgium

Location

Novartis Investigative Site

Ostend, 8400, Belgium

Location

Novartis Investigative Site

Wavre, 1301, Belgium

Location

Novartis Investigative Site

Burlington, Ontario, L7N 3V2, Canada

Location

Novartis Investigative Site

Mississauga, Ontario, L5M 2V8, Canada

Location

Novartis Investigative Site

Toronto, Ontario, M5G1N8, Canada

Location

Novartis Investigative Site

Toronto, Ontario, M6H 3M2, Canada

Location

Novartis Investigative Site

Laval, Quebec, H7S 2M5, Canada

Location

Novartis Investigative Site

Mirabel, Quebec, J7J 2K8, Canada

Location

Novartis Investigative Site

Saint-Charles-Borromée, Quebec, J6E 6J2, Canada

Location

Novartis Investigative Site

Berlin, Germany, 12099, Germany

Location

Novartis Investigative Site

Leipzig, Germany, 04207, Germany

Location

Novartis Investigative Site

Mainz, Germany, D-55101, Germany

Location

Novartis Investigative Site

Potsdam, Germany, 14467, Germany

Location

Novartis Investigative Site

Cottbus, Saxony, 03050, Germany

Location

Novartis Investigative Site

Aschaffenburg, 63739, Germany

Location

Novartis Investigative Site

Berlin, 10789, Germany

Location

Novartis Investigative Site

Berlin, 12203, Germany

Location

Novartis Investigative Site

Berlin, 13156, Germany

Location

Novartis Investigative Site

Frankfurt, 60389, Germany

Location

Novartis Investigative Site

Halle, 06108, Germany

Location

Novartis Investigative Site

Hanover, 30317, Germany

Location

Novartis Investigative Site

Leipzig, 04103, Germany

Location

Novartis Investigative Site

Leipzig, 04275, Germany

Location

Novartis Investigative Site

Leipzig, 04357, Germany

Location

Novartis Investigative Site

Potsdam, 14478, Germany

Location

Novartis Investigative Site

Rheine, 48431, Germany

Location

Novartis Investigative Site

Rüdersdorf, 15562, Germany

Location

Novartis Investigative Site

Málaga, Andalusia, 29010, Spain

Location

Novartis Investigative Site

Mérida, Badajoz, 06800, Spain

Location

Novartis Investigative Site

Badalona, Barcelona, 08914, Spain

Location

Novartis Investigative Site

Ponferrada, Leon, 24400, Spain

Location

Novartis Investigative Site

Madrid, Madrid, 28007, Spain

Location

Novartis Investigative Site

Salford, Manchester, M6 8HD, United Kingdom

Location

Novartis Investigative Site

Bradford, BD9 6RJ, United Kingdom

Location

Novartis Investigative Site

Glasgow, G11 6NT, United Kingdom

Location

Novartis Investigative Site

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Novartis Investigative Site

Portsmouth, PO6 3AD, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 24176997 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Dyspnea

Interventions

indacaterol-glycopyrronium combination; Tiotropium Bromide; Albuterol

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiration Disorders; Signs and Symptoms, Respiratory; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring; Ethanolamines; Amino Alcohols; Alcohols; Amines; Phenethylamines; Ethylamines

Results Point of Contact

• Title: Study director
• Organization: Novartis

41 61 324 1111

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2011
• First Posted: December 12, 2011
• Study Start: October 1, 2011
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: December 24, 2013
• Results First Posted: December 24, 2013

Record last verified: 2013-11

Locations

ES (5); GB (5); DE (18); CA (7); BE (8)