A 26-week Treatment Multi-center, Randomized, Double-blind, Parallel-group, Placebo and Active Controlled (Open Label) Study to Assess the Efficacy, Safety and Tolerability of QVA149 (110/50 μg q.d.) in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)
Overview
- Phase
- Phase 3
- Intervention
- indacaterol and glycopyrronium (QVA149)
- Conditions
- Chronic Obstructive Pulmonary Disease (COPD)
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 2144
- Locations
- 4
- Primary Endpoint
- Trough Forced Expiratory Volume In One Second (FEV1) After 26 Weeks of Treatment
- Status
- Completed
- Last Updated
- 12 years ago
Overview
Brief Summary
The purpose of this study is to provide pivotal efficacy and safety data for QVA149 in patients with moderate to severe COPD.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female adults aged ≥40 yrs
- •Smoking history of at least 10 pack years
- •Diagnosis of COPD (moderate-to-severe as classified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines, 2008)
- •Post-bronchodilator FEV1 \< 80% and ≥ 30% of the predicted normal value and post-bronchodilator FEV1/FVC (forced vital capacity) \<70%
Exclusion Criteria
- •Patients who have had a respiratory tract infection within 4 weeks prior to Visit 1
- •Patients with concomitant pulmonary disease
- •Patients with a history of asthma
- •Any patient with lung cancer or a history of lung cancer
- •Patients with a history of certain cardiovascular co-morbid conditions
- •Patients with a known history and diagnosis of alpha-1 antitrypsin deficiency
- •Patients in the active phase of a supervised pulmonary rehabilitation program
- •Patients contraindicated for inhaled anticholinergic agents and β2 agonists
- •Other protocol-defined inclusion/exclusion criteria may apply
Arms & Interventions
indacaterol and glycopyrronium (QVA149)
QVA149 110/50 μg capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDPPI) for 26 weeks. Participants remained on a stable dose of inhaled corticosteroid (ICS) and salbutamol/albuterol was available for use as rescue medication throughout the study.
Intervention: indacaterol and glycopyrronium (QVA149)
glycopyrronium (NVA237)
NVA237 50 μg capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDDPI) for 26 weeks. Participants remained on a stable dose of inhaled corticosteroid (ICS) and salbutamol/albuterol was available for use as rescue medication throughout the study.
Intervention: glycopyrronium (NVA237)
indacaterol (QAB149)
QAB149 150 μg capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDDPI) for 26 weeks. Participants remained on a stable dose of inhaled corticosteroid (ICS) and salbutamol/albuterol was available for use as rescue medication throughout the study.
Intervention: indacaterol (QAB149)
tiotropium
Tiotropium 18 μg capsules for inhalation delivered once daily via HandiHaler® device for 26 weeks. Participants remained on a stable dose of inhaled corticosteroid (ICS) and salbutamol/albuterol was available for use as rescue medication throughout the study.
Intervention: tiotropium
Placebo
Matching placebo capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDDPI) for 26 weeks. Participants remained on a stable dose of inhaled corticosteroid (ICS) and salbutamol/albuterol was available for use as rescue medication throughout the study.
Intervention: placebo
Outcomes
Primary Outcomes
Trough Forced Expiratory Volume In One Second (FEV1) After 26 Weeks of Treatment
Time Frame: 23 hours 15 minutes and 23 hour 45 minute post-dose Week 26
Spirometry was performed according to internationally accepted standards. Trough FEV1 was defined as the mean of the 23 hour 15 minute and 23 hour 45 minute post-dose values. A mixed model was used with treatment as a fixed effect with baseline FEV1 and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.
Secondary Outcomes
- Transitional Dyspnea Index (TDI) Focal Score at Week 26(Week 26)
- Trough Forced Expiratory Volume In One Second (FEV1) After 26 Weeks of Treatment With QVA149, QAB149 and NVA237 Compared to Placebo(23 hours 15 minutes and 23 hour 45 minute post-dose Week 26)
- Trough Forced Expiratory Volume In One Second (FEV1) After 26 Weeks of Treatment With QVA149 Compared to Tiotropium(23 hours 15 minutes and 23 hour 45 minute post-dose Week 26)
- St. George's Respiratory Questionnaire (SGRQ) Total Score After 12 and 26 Weeks of Treatment(Week 12, Week 26)
- Percentage of Patients With a Clinically Important Improvement of at Least 1 Point in TDI Focal Score After 26 Weeks of Treatment(Baseline, Week 26)
- Percentage of "Days With no Rescue Medication Use" Over 26 Weeks(26 Weeks)
- St. George's Respiratory Questionnaire (SGRQ) Total Score at Week 26(26 weeks)
- Baseline Transitional Dyspnea Index (BDI/TDI) Focal Score at Week 12 and Week 26(Baseline, Week 12, Week 26)
- Percentage of Days With "No Daytime Symptoms" Over 26 Weeks(26 Weeks)
- Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 12 Hours at Day 1 and Week 26(From 5 minutes to 12 hours post-dose Day 1 and Week 26)
- Percentage of Patients With a Clinically Important Improvement From Baseline of at Least 4 Units in the SGRQ Total Score After 26 Weeks of Treatment(Baseline, Week 26)
- Percentage of "Days Able to Perform Usual Daily Activities" Over 26 Weeks(26 Weeks)
- Change From Baseline (BL) in the Daytime and Night Time Rescue Medication Use (Number of Puffs) Over 26 Weeks(Baseline, Week 26)
- Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 23 Hours 45 Minutes at Week 26(From 5 minutes to 23 hours 45 minutes post-dose Week 26)
- Percentage of Patients With at Least One Moderate or Severe COPD Exacerbation Over the 26 Week Treatment Period(26 Weeks)
- Percentage of Participants With COPD Exacerbations Requiring Hospitalization or Treatment With Systemic Corticosteroids and/or Antibiotics But no Hospitalization(26 Weeks)
- Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication Over 26 Weeks(Baseline, Week 26)
- Percentage of Nights With "No Night Time Awakenings" Over 26 Weeks(26 Weeks)
- Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication at Week 12 and Week 26(Baseline, Week 12, Week 26)
- Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours at Day 1 and Week 26(From 5 minutes to 4 hours post-dose Day 1 and Week 26)
- 24 Hour Holter Monitoring in a Subset of Patients(Week 12, Week 26)
- Rate of Moderate or Severe COPD Exacerbation(26 Weeks)