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

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

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

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Drug: QVA149; Drug: Placebo to tiotropium; Drug: Placebo to formoterol; Drug: Tiotropium; Drug: Formoterol; Drug: Placebo to QVA149

• Study Type: Interventional
• Enrollment (Actual): 934
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Aschaffenburg, Germany, 63739
    • Novartis Investigative Site
  • Augsburg, Germany, 86156
    • Novartis Investigative Site
  • Bad Neustadt, Germany, 97616
    • Novartis Investigative Site
  • Bad Woerishofen, Germany, 86825
    • Novartis Investigative Site
  • Bamberg, Germany, 96049
    • Novartis Investigative Site
  • Bensheim, Germany, 64625
    • Novartis Investigative Site
  • Bergisch Gladbach, Germany, 51429
    • Novartis Investigative Site
  • Berlin, Germany, 12043
    • Novartis Investigative Site
  • Berlin, Germany, 12203
    • Novartis Investigative Site
  • Berlin, Germany, 12687
    • Novartis Investigative Site
  • Berlin, Germany, 13086
    • Novartis Investigative Site
  • Berlin, Germany, 10717
    • Novartis Investigative Site
  • Berlin, Germany, 10367
    • Novartis Investigative Site
  • Berlin, Germany, 13156
    • Novartis Investigative Site
  • Berlin, Germany, 14050
    • Novartis Investigative Site
  • Berlin, Germany, 10969
    • Novartis Investigative Site
  • Berlin, Germany, 12165
    • Novartis Investigative Site
  • Berlin, Germany, 10789
    • Novartis Investigative Site
  • Berlin, Germany, 14059
    • Novartis Investigative Site
  • Berlin, Germany, 12099
    • Novartis Investigative Site
  • Berlin, Germany, 13057
    • Novartis Investigative Site
  • Berlin, Germany, 13507
    • Novartis Investigative Site
  • Berlin, Germany, 10115
    • Novartis Investigative Site
  • Berlin, Germany, 13465
    • Novartis Investigative Site
  • Bielefeld, Germany, 33617
    • Novartis Investigative Site
  • Bochum, Germany, 44787
    • Novartis Investigative Site
  • Bonn, Germany, 53119
    • Novartis Investigative Site
  • Bonn, Germany, 53123
    • Novartis Investigative Site
  • Borna, Germany, 04552
    • Novartis Investigative Site
  • Chemnitz, Germany, 09130
    • Novartis Investigative Site
  • Delitzsch, Germany, 04509
    • Novartis Investigative Site
  • Donaustauf, Germany, 93093
    • Novartis Investigative Site
  • Dortmund, Germany, 44135
    • Novartis Investigative Site
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Dresden, Germany, 01069
    • Novartis Investigative Site
  • Dueren, Germany, 52349
    • Novartis Investigative Site
  • Duisburg, Germany, 47057
    • Novartis Investigative Site
  • Düsseldorf, Germany, 40489
    • Novartis Investigative Site
  • Eggenfelden, Germany, 84307
    • Novartis Investigative Site
  • Eisenach, Germany, 99817
    • Novartis Investigative Site
  • Erlangen, Germany, 91052
    • Novartis Investigative Site
  • Eschwege, Germany, 37269
    • Novartis Investigative Site
  • Essen, Germany, 45276
    • Novartis Investigative Site
  • Essen, Germany, 45138
    • Novartis Investigative Site
  • Euskirchen, Germany, 53879
    • Novartis Investigative Site
  • Forchheim, Germany, 91301
    • Novartis Investigative Site
  • Frankfurt, Germany, 60596
    • Novartis Investigative Site
  • Frankfurt, Germany, 60389
    • Novartis Investigative Site
  • Fulda, Germany, 36039
    • Novartis Investigative Site
  • Gauting, Germany, 82131
    • Novartis Investigative Site
  • Geesthacht, Germany, 22502
    • Novartis Investigative Site
  • Gelnhausen, Germany, 63571
    • Novartis Investigative Site
  • Gelsenkirchen, Germany, 45879
    • Novartis Investigative Site
  • Grosshansdorf, Germany, 22947
    • Novartis Investigative Site
  • Gummersbach, Germany, 51643
    • Novartis Investigative Site
  • Göttingen, Germany, 37075
    • Novartis Investigative Site
  • Güstrow, Germany, 18273
    • Novartis Investigative Site
  • Hagen, Germany, 59065
    • Novartis Investigative Site
  • Halberstadt, Germany, 38820
    • Novartis Investigative Site
  • Halle, Germany, 06108
    • Novartis Investigative Site
  • Hamburg, Germany, 20354
    • Novartis Investigative Site
  • Hamburg, Germany, 20357
    • Novartis Investigative Site
  • Hamburg, Germany, 22299
    • Novartis Investigative Site
  • Hamburg, Germany, 22527
    • Novartis Investigative Site
  • Hannover, Germany, 30163
    • Novartis Investigative Site
  • Hannover, Germany, 30419
    • Novartis Investigative Site
  • Hannover, Germany, 30317
    • Novartis Investigative Site
  • Hannover Münden, Germany, 34346
    • Novartis Investigative Site
  • Heidelberg, Germany, 69115
    • Novartis Investigative Site
  • Heidelberg, Germany, 69117
    • Novartis Investigative Site
  • Hettstedt, Germany, 06333
    • Novartis Investigative Site
  • Hildesheim, Germany, 31134
    • Novartis Investigative Site
  • Höchstadt, Germany, 91315
    • Novartis Investigative Site
  • Kamen, Germany, 59174
    • Novartis Investigative Site
  • Kamenz, Germany, 01917
    • Novartis Investigative Site
  • Kassel, Germany, 34121
    • Novartis Investigative Site
  • Koeln, Germany, 51069
    • Novartis Investigative Site
  • Krefeld, Germany, 47798
    • Novartis Investigative Site
  • Köln, Germany, 51605
    • Novartis Investigative Site
  • Landsberg, Germany, 86899
    • Novartis Investigative Site
  • Leipzig, Germany, 04207
    • Novartis Investigative Site
  • Leipzig, Germany, 04357
    • Novartis Investigative Site
  • Leipzig, Germany, 04103
    • Novartis Investigative Site
  • Leipzig, Germany, 04275
    • Novartis Investigative Site
  • Luedenscheid, Germany, 58507
    • Novartis Investigative Site
  • Lübeck, Germany, 23558
    • Novartis Investigative Site
  • Mainz, Germany, 55131
    • Novartis Investigative Site
  • Mainz, Germany, 55116
    • Novartis Investigative Site
  • Mannheim, Germany, 68165
    • Novartis Investigative Site
  • Marburg, Germany, 35037
    • Novartis Investigative Site
  • Menden, Germany, 58706
    • Novartis Investigative Site
  • Minden, Germany, 32423
    • Novartis Investigative Site
  • Muenchen, Germany, 80539
    • Novartis Investigative Site
  • Muenchen, Germany, 81677
    • Novartis Investigative Site
  • München, Germany, 80335
    • Novartis Investigative Site
  • Münster, Germany, 48145
    • Novartis Investigative Site
  • Münster, Germany, 48147
    • Novartis Investigative Site
  • Neu Isenburg, Germany, 63263
    • Novartis Investigative Site
  • Neu-Ulm, Germany, 89231
    • Novartis Investigative Site
  • Neumünster, Germany, 24534
    • Novartis Investigative Site
  • Neunkirchen, Germany, 66539
    • Novartis Investigative Site
  • Neuruppin, Germany, 16816
    • Novartis Investigative Site
  • Neuss, Germany, 41462
    • Novartis Investigative Site
  • Oranienburg, Germany, 16515
    • Novartis Investigative Site
  • Oschatz, Germany, 04758
    • Novartis Investigative Site
  • Oschersleben, Germany, 39387
    • Novartis Investigative Site
  • Osnabrück, Germany, 49074
    • Novartis Investigative Site
  • Peine, Germany, 31224
    • Novartis Investigative Site
  • Potsdam, Germany, 14467
    • Novartis Investigative Site
  • Potsdam, Germany, 14469
    • Novartis Investigative Site
  • Potsdam, Germany, 14478
    • Novartis Investigative Site
  • Prien a. Chiemsee, Germany, 83209
    • Novartis Investigative Site
  • Radebeul, Germany, 01445
    • Novartis Investigative Site
  • Rathenow, Germany, 14712
    • Novartis Investigative Site
  • Ratingen, Germany, 40878
    • Novartis Investigative Site
  • Reinfeld, Germany, 23858
    • Novartis Investigative Site
  • Rheine, Germany, 48431
    • Novartis Investigative Site
  • Roth, Germany, 91154
    • Novartis Investigative Site
  • Rüdersdorf, Germany, 15562
    • Novartis Investigative Site
  • Rüsselsheim, Germany, 65428
    • Novartis Investigative Site
  • Saarbruecken, Germany, 66111
    • Novartis Investigative Site
  • Saarlouis, Germany, 66740
    • Novartis Investigative Site
  • Schleswig, Germany, 24837
    • Novartis Investigative Site
  • Schwabach, Germany, 91126
    • Novartis Investigative Site
  • Siegen, Germany, 57072
    • Novartis Investigative Site
  • Singen, Germany, 76224
    • Novartis Investigative Site
  • Solingen, Germany, 42651
    • Novartis Investigative Site
  • Solingen, Germany, 42665
    • Novartis Investigative Site
  • Sonneberg, Germany, 96515
    • Novartis Investigative Site
  • Stade, Germany, 21680
    • Novartis Investigative Site
  • Teterow, Germany, 17166
    • Novartis Investigative Site
  • Teuchern, Germany, 06682
    • Novartis Investigative Site
  • Ulm, Germany, 89073
    • Novartis Investigative Site
  • Vöhringen, Germany, 89269
    • Novartis Investigative Site
  • Wedel, Germany, 22880
    • Novartis Investigative Site
  • Weyhe, Germany, 28844
    • Novartis Investigative Site
  • Wiesloch, Germany, 69168
    • Novartis Investigative Site
  • Wissen, Germany, 57537
    • Novartis Investigative Site
  • Witten, Germany, 58452
    • Novartis Investigative Site
  • Wuppertal, Germany, 42117
    • Novartis Investigative Site
  • Zerbst, Germany, 39261
    • Novartis Investigative Site
  • NRW
    • Koblenz, NRW, Germany, 56068
      • Novartis Investigative Site
  • Sachsen
    • Cottbus, Sachsen, Germany, 03050
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: QVA149 plus placebo to tiotropium and placebo to formoterol; QVA149 110/50µg, once daily for inhalation use plus placebo to tiotropium, once daily for inhalation use and placebo to formoterol, twice daily for inhalation use.	Drug: QVA149; QVA149 110/50µg, once daily (q.d.) is administered via a single-dose dry powder inhaler; Drug: 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; Drug: 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.
ACTIVE_COMPARATOR: Tiotropium plus Formoterol and placebo to QVA149; Tiotropium 18µg, once daily for inhalation use plus Formoterol 12µg, twice daily for inhalation use and placebo to QVA149, once daily for inhalation use.	Drug: Tiotropium; Tiotropium 18µg, once daily is administered via the manufacturer's proprietary inhalation device.; Drug: Formoterol; Formoterol 12µg, twice daily is administered via the manufacturer's proprietary inhalation device.; Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (ACTUAL): April 1, 2013
• Study Completion (ACTUAL): April 1, 2013

Study Registration Dates

• First Submitted: April 6, 2012
• First Submitted That Met QC Criteria: April 6, 2012
• First Posted (ESTIMATE): April 10, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): May 22, 2014
• Last Update Submitted That Met QC Criteria: May 19, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: COPD; QVA149; Formoterol; Tiotropium; Health related quality of life
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Adrenergic Agonists; Adjuvants, Anesthesia; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Glycopyrrolate; Tiotropium Bromide; Formoterol Fumarate
• Other Study ID Numbers: CQVA149ADE01; 2011-004870-26 (EUDRACT_NUMBER)