The Effect of QVA149 on Health Related Quality of Life in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Chronic Obstructive Pulmonary Disease (COPD) Clinical Trial

— QUANTIFY  

Official title:

A 26-week Treatment, Multicenter, Randomized, Parallel Group, Blinded Study to Assess the Efficacy and Safety of QVA149 in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease Using Tiotropium Plus Formoterol as Control

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01574651
• Other study ID #: CQVA149ADE01
• Secondary ID: 2011-004870-26
• Status: Completed
• Phase: Phase 3
• First received: April 6, 2012
• Last updated: May 19, 2014
• Start date: May 2012
• Est. completion date: April 2013

Study information

• Verified date: May 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM)
• Study type: Interventional

Clinical Trial Summary

This study will assess the efficacy and safety of QVA149 compared to tiotropium plus formoterol in patients with moderate to severe COPD.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 934
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Male or female adults aged = 40 yrs

• Patients with moderate to severe chronic obstructive pulmonary disease (GOLD 2010 guidelines)

• Smoking history of at least 10 pack years

• Post-bronchodilator FEV1 < 80% and =30% of the predicted normal value and post-bronchodilator FEV1/FVC (forced vital capacity) <70%

Exclusion Criteria:

• Pregnant women or nursing mothers or women of child-bearing potential not using adequate contraception

• 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: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease (COPD)
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• QVA149
QVA149 110/50µg, once daily (q.d.) is administered via a single-dose dry powder inhaler
• Placebo to tiotropium
Placebo to tiotropium capsules daily (q.d.) for inhalation, delivered via proprietary inhaler (Handihaler®). Placebo tiotropium inhalation capsules were matched in size and color to tiotropium 18 µg q.d. inhalation capsules
• Placebo to formoterol
Placebo to formoterol capsules twice daily (b.i.d) delivered via Aerolizer® device. Placebo formoterol inhalation capsules were equally matched in size, shape and color to formoterol 12 µg b.i.d. inhalation capsules.
• Tiotropium
Tiotropium 18µg, once daily is administered via the manufacturer's proprietary inhalation device.
• Formoterol
Formoterol 12µg, twice daily is administered via the manufacturer's proprietary inhalation device.
• Placebo to QVA149
Placebo to QVA149 is administered via a single-dose dry powder inhaler. Placebo QVA149 inhalation capsules were equally matched in size, shape and color to QVA149 110/50 µg q.d. inhalation capsules

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Aschaffenburg
Germany	Novartis Investigative Site	Augsburg
Germany	Novartis Investigative Site	Bad Neustadt
Germany	Novartis Investigative Site	Bad Woerishofen
Germany	Novartis Investigative Site	Bamberg
Germany	Novartis Investigative Site	Bensheim
Germany	Novartis Investigative Site	Bergisch Gladbach
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bielefeld
Germany	Novartis Investigative Site	Bochum
Germany	Novartis Investigative Site	Bonn
Germany	Novartis Investigative Site	Bonn
Germany	Novartis Investigative Site	Borna
Germany	Novartis Investigative Site	Chemnitz
Germany	Novartis Investigative Site	Cottbus	Sachsen
Germany	Novartis Investigative Site	Delitzsch
Germany	Novartis Investigative Site	Donaustauf
Germany	Novartis Investigative Site	Dortmund
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Dueren
Germany	Novartis Investigative Site	Duisburg
Germany	Novartis Investigative Site	Düsseldorf
Germany	Novartis Investigative Site	Eggenfelden
Germany	Novartis Investigative Site	Eisenach
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Eschwege
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Euskirchen
Germany	Novartis Investigative Site	Forchheim
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Fulda
Germany	Novartis Investigative Site	Gauting
Germany	Novartis Investigative Site	Geesthacht
Germany	Novartis Investigative Site	Gelnhausen
Germany	Novartis Investigative Site	Gelsenkirchen
Germany	Novartis Investigative Site	Göttingen
Germany	Novartis Investigative Site	Grosshansdorf
Germany	Novartis Investigative Site	Gummersbach
Germany	Novartis Investigative Site	Güstrow
Germany	Novartis Investigative Site	Hagen
Germany	Novartis Investigative Site	Halberstadt
Germany	Novartis Investigative Site	Halle
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Hannover Münden
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Hettstedt
Germany	Novartis Investigative Site	Hildesheim
Germany	Novartis Investigative Site	Höchstadt
Germany	Novartis Investigative Site	Kamen
Germany	Novartis Investigative Site	Kamenz
Germany	Novartis Investigative Site	Kassel
Germany	Novartis Investigative Site	Koblenz	NRW
Germany	Novartis Investigative Site	Koeln
Germany	Novartis Investigative Site	Köln
Germany	Novartis Investigative Site	Krefeld
Germany	Novartis Investigative Site	Landsberg
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Lübeck
Germany	Novartis Investigative Site	Luedenscheid
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Mannheim
Germany	Novartis Investigative Site	Marburg
Germany	Novartis Investigative Site	Menden
Germany	Novartis Investigative Site	Minden
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	München
Germany	Novartis Investigative Site	Münster
Germany	Novartis Investigative Site	Münster
Germany	Novartis Investigative Site	Neu Isenburg
Germany	Novartis Investigative Site	Neu-Ulm
Germany	Novartis Investigative Site	Neumünster
Germany	Novartis Investigative Site	Neunkirchen
Germany	Novartis Investigative Site	Neuruppin
Germany	Novartis Investigative Site	Neuss
Germany	Novartis Investigative Site	Oranienburg
Germany	Novartis Investigative Site	Oschatz
Germany	Novartis Investigative Site	Oschersleben
Germany	Novartis Investigative Site	Osnabrück
Germany	Novartis Investigative Site	Peine
Germany	Novartis Investigative Site	Potsdam
Germany	Novartis Investigative Site	Potsdam
Germany	Novartis Investigative Site	Potsdam
Germany	Novartis Investigative Site	Prien a. Chiemsee
Germany	Novartis Investigative Site	Radebeul
Germany	Novartis Investigative Site	Rathenow
Germany	Novartis Investigative Site	Ratingen
Germany	Novartis Investigative Site	Reinfeld
Germany	Novartis Investigative Site	Rheine
Germany	Novartis Investigative Site	Roth
Germany	Novartis Investigative Site	Rüdersdorf
Germany	Novartis Investigative Site	Rüsselsheim
Germany	Novartis Investigative Site	Saarbruecken
Germany	Novartis Investigative Site	Saarlouis
Germany	Novartis Investigative Site	Schleswig
Germany	Novartis Investigative Site	Schwabach
Germany	Novartis Investigative Site	Siegen
Germany	Novartis Investigative Site	Singen
Germany	Novartis Investigative Site	Solingen
Germany	Novartis Investigative Site	Solingen
Germany	Novartis Investigative Site	Sonneberg
Germany	Novartis Investigative Site	Stade
Germany	Novartis Investigative Site	Teterow
Germany	Novartis Investigative Site	Teuchern
Germany	Novartis Investigative Site	Ulm
Germany	Novartis Investigative Site	Vöhringen
Germany	Novartis Investigative Site	Wedel
Germany	Novartis Investigative Site	Weyhe
Germany	Novartis Investigative Site	Wiesloch
Germany	Novartis Investigative Site	Wissen
Germany	Novartis Investigative Site	Witten
Germany	Novartis Investigative Site	Wuppertal
Germany	Novartis Investigative Site	Zerbst

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	St. George's Respiratory Questionnaire (SGRQ-C) Total Score After 26 Weeks of Treatment (Non-inferiority Analysis).	SGRQ is a health related quality of life questionnaire consisting of 40 items in three areas: symptoms (respiratory symptoms and severity), activity (activities that cause or are limited by breathlessness) and impacts (social functioning and psychological disturbances due to airway disease). The total score is 0 to 100 with a higher score indicating poorer health status. For patients who completed the study but with missing SGRQ-C during treatment, the missing SGRQ-C were replaced by the last observation carried forward (LOCF). Symptom scores were expected to improve over treatment, therefore the replacement of missing values with earlier measurements did not result in overoptimistic imputation and this procedure could be regarded as conservative.	Baseline, week 26	No
Secondary	St. George's Respiratory Questionnaire (SGRQ-C) Total Score After 26 Weeks of Treatment (Superiority Analysis).	SGRQ is a health related quality of life questionnaire consisting of 40 items in three areas: symptoms (respiratory symptoms and severity), activity (activities that cause or are limited by breathlessness) and impacts (social functioning and psychological disturbances due to airway disease). The total score is 0 to 100 with a higher score indicating poorer health status. For patients who completed the study but with missing SGRQ-C during treatment, the missing SGRQ-C were replaced by the last observation carried forward (LOCF). Symptom scores were expected to improve over treatment, therefore the replacement of missing values with earlier measurements did not result in overoptimistic imputation and this procedure could be regarded as conservative. Superiority of QVA 110/50 µg to tiotropium 18 µg q.d. plus formoterol 12 µg b.i.d. in terms of health related quality of life as assessed by St George's Respiratory Questionnaire (SGRQ-C) after 26 weeks of treatment	Baseline, week 26	No
Secondary	Transition Dyspnea Index (TDI) Focal Score After 26 Weeks of Treatment.	Baseline Dyspnea Index (BDI)/Transition Dyspnea Index (TDI) focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort and captures changes from baseline. BDI was measured at day 1 prior to the first dose with domain scores ranging from 0=very severe to 4=no impairment and a total score ranging from 0 to 12(best). TDI captures changes from baseline. Each domain is scored from -3=major deterioration to 3=major improvement to give an overall TDI focal score of -9 to 9. Higher numbers indicate a better score. missing values were replaced by the latest observed value (LOCF)	Week 26	No
Secondary	Percent of Participants With at Least One Exacerbation Requiring Systemic Corticosteroids and/or Antibiotics Over 26 Weeks	The percent of participants with at least one moderate exacerbation within the 26 weeks that required systemic corticosteroids and/or antibiotics during the treatment	Week 26	No
Secondary	Percent of Participants With at Least One Exacerbation Requiring Hospitalization	The percent of patients with at least one severe exacerbation within the 26 weeks that required hospitalization. COPD exacerbations were considered to be severe if hospitalization were required.	Week 26	No
Secondary	Time- Event Analysis, Number of Participants With at Least One COPD Exacerbation (Moderate or Severe) During the Treatment Period	The number of participants with at least one moderate or severe COPD exacerbation. COPD exacerbations are considered to be moderate if treatment with systemic corticosteroids and/or antibiotics was required. COPD exacerbations are considered to be severe if hospitalizations were required.	Week 26	No
Secondary	Trough FEV1 at Baseline and Week 26	Trough FEV1 is the mean value of FEV1 (forced expiratory volume in one second) measured at 23:15h and 23:45h after the morning doses. The baseline value was measured at day 1 prior to the first dose.	Baseline, Week 26	No
Secondary	FEV1 30 Min After the Morning Dose at Baseline and Week 26	FEV1 30min is the forced expiratory volume in one second measured 30 min after the morning dose.	Baseline, Week 26	No
Secondary	Symptoms Score Reported by the Patients Using Part I "Symptoms" of SGRO-C	Part I of the SGRQ-C covers "symptoms" and is concerned with respiratory symptoms, their frequency and severity. Each questionnaire response has a unique empirically derived "weight". A score was calculated from these weights. The lowest possible value is zero and the highest 100. A higher value corresponds to greater impairment of health status.	Baseline, Week 26	No