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

Phase 3

Completed

Conditions: Chronic Obstructive Pulmonary Disease (COPD)

Interventions: Drug: QVA149
Drug: Tiotropium
Drug: Placebo to tiotropium
Drug: Formoterol
Drug: Placebo to QVA149
Drug: Placebo to formoterol

Registration Number: NCT01574651

Lead Sponsor: Novartis Pharmaceuticals

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 934

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

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
QVA149 plus placebo to tiotropium and placebo to formoterol	QVA149	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.
Tiotropium plus Formoterol and placebo to QVA149	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.
QVA149 plus placebo to tiotropium and placebo to formoterol	Placebo to tiotropium	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.
QVA149 plus placebo to tiotropium and placebo to formoterol	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.
Tiotropium plus Formoterol and placebo to QVA149	Tiotropium	Tiotropium 18µg, once daily for inhalation use plus Formoterol 12µg, twice daily for inhalation use and placebo to QVA149, once daily for inhalation use.
Tiotropium plus Formoterol and placebo to QVA149	Formoterol	Tiotropium 18µg, once daily for inhalation use plus Formoterol 12µg, twice daily for inhalation use and placebo to QVA149, once daily for inhalation use.

Primary Outcome Measures

Name	Time	Method
St. George's Respiratory Questionnaire (SGRQ-C) Total Score After 26 Weeks of Treatment (Non-inferiority Analysis).	Baseline, week 26	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

Name	Time	Method
St. George's Respiratory Questionnaire (SGRQ-C) Total Score After 26 Weeks of Treatment (Superiority Analysis).	Baseline, week 26	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.	Week 26	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	Week 26	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	Week 26	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	Week 26	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	Baseline, 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.
FEV1 30 Min After the Morning Dose at Baseline and Week 26	Baseline, Week 26	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	Baseline, Week 26	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.