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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01574651
First received: April 6, 2012
Last updated: May 19, 2014
Last verified: May 2014
  Purpose

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


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease (COPD)
Drug: QVA149
Drug: Placebo to tiotropium
Drug: Placebo to formoterol
Drug: Tiotropium
Drug: Formoterol
Drug: Placebo to QVA149
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • St. George's Respiratory Questionnaire (SGRQ-C) Total Score After 26 Weeks of Treatment (Non-inferiority Analysis). [ Time Frame: Baseline, week 26 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • St. George's Respiratory Questionnaire (SGRQ-C) Total Score After 26 Weeks of Treatment (Superiority Analysis). [ Time Frame: Baseline, week 26 ] [ Designated as safety issue: No ]
    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

  • Transition Dyspnea Index (TDI) Focal Score After 26 Weeks of Treatment. [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    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)

  • Percent of Participants With at Least One Exacerbation Requiring Systemic Corticosteroids and/or Antibiotics Over 26 Weeks [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    The percent of participants with at least one moderate exacerbation within the 26 weeks that required systemic corticosteroids and/or antibiotics during the treatment

  • Percent of Participants With at Least One Exacerbation Requiring Hospitalization [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    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.

  • Time- Event Analysis, Number of Participants With at Least One COPD Exacerbation (Moderate or Severe) During the Treatment Period [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    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.

  • Trough FEV1 at Baseline and Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
    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.

  • FEV1 30 Min After the Morning Dose at Baseline and Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
    FEV1 30min is the forced expiratory volume in one second measured 30 min after the morning dose.

  • Symptoms Score Reported by the Patients Using Part I "Symptoms" of SGRO-C [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
    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.


Enrollment: 934
Study Start Date: May 2012
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01574651

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Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01574651     History of Changes
Other Study ID Numbers: CQVA149ADE01, 2011-004870-26
Study First Received: April 6, 2012
Results First Received: March 27, 2014
Last Updated: May 19, 2014
Health Authority: Germany: Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM)

Keywords provided by Novartis:
QVA149
Health related quality of life
Formoterol
Tiotropium
COPD

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Formoterol
Tiotropium
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Parasympatholytics
Cholinergic Antagonists
Cholinergic Agents

ClinicalTrials.gov processed this record on September 15, 2014