A 64-week Treatment, Multi-center, Randomized, Double-blind, Parallel-group, Active Controlled Study to Evaluate the Effect of QVA149 (110/50 μg o.d.) vs NVA237 (50 μg o.d.) and Open-label Tiotropium (18 μg o.d.) on COPD Exacerbations in Patients With Severe to Very Severe Chronic Obstructive Pulmonary Disease (COPD)
Overview
- Phase
- Phase 3
- Intervention
- QVA149
- Conditions
- Chronic Obstructive Pulmonary Disease
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 2224
- Locations
- 1
- Primary Endpoint
- Rate of Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations in QVA149 and NVA237 Treatment Arms During the Treatment Period.
- Status
- Completed
- Last Updated
- 12 years ago
Overview
Brief Summary
This study is designed to assess the effect of once-daily QVA149 on COPD exacerbations in patients with severe to very severe COPD.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- •Pregnant women or nursing mothers (pregnancy confirmed by positive urine pregnancy test).
- •Women of child-bearing potential
- •Patients requiring long term oxygen therapy (\> 15 h a day) on a daily basis for chronic hypoxemia.
- •Patients who had a COPD exacerbation that required treatment with antibiotics, systemic steroids (oral or intravenous) or hospitalization in the 6 weeks prior to visit 1 or between visit 1 (Day -21) and Visit 3 (Day 1).
- •Patients who developed a COPD exacerbation during a period between visit 1 and 3 were ineligible but were permitted to be re-screened after a minimum of 6 weeks after the resolution of the COPD exacerbation.
- •Patients who had a respiratory tract infection within 4 weeks prior to visit 1 (Day -21)
- •Patients who developed an upper or lower respiratory tract infection during the screening period (up to visit 3 (Day 1) were not eligible, but were permitted to be re-screened 4 weeks after the resolution of the respiratory tract infection
- •Patients with concomitant pulmonary disease, e.g. pulmonary tuberculosis (unless confirmed by chest x-ray to be no longer active), clinically significant bronchiectasis, sarcoidosis, interstitial lung disorder or pulmonary hypertension.
- •Patients with lung lobectomy, or lung volume reduction or lung transplantation.
- •Patients who, in the judgment of the investigator, have a clinically relevant laboratory abnormality or a clinically significant condition such as (but not limited to):
Arms & Interventions
QVA149
QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
Intervention: QVA149
QVA149
QVA149 110/50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
Intervention: Salbutamol/albuterol
NVA237
NVA237 50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
Intervention: NVA237
NVA237
NVA237 50 μg capsules for inhalation, once daily delivered via Novartis Single Dose Dry Powder Inhaler (SDDPI) for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
Intervention: Salbutamol/albuterol
open-label tiotropium
Open-label tiotropium bromide 18 μg capsules for inhalation once daily delivered via HandiHaler® device for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
Intervention: tiotropium
open-label tiotropium
Open-label tiotropium bromide 18 μg capsules for inhalation once daily delivered via HandiHaler® device for at least 64 weeks of double blind treatment period (study duration was up to 76 weeks). Salbutamol/albuterol was available for rescue medication use throughout the study.
Intervention: Salbutamol/albuterol
Outcomes
Primary Outcomes
Rate of Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations in QVA149 and NVA237 Treatment Arms During the Treatment Period.
Time Frame: 64 weeks
A Chronic Obstructive Pulmonary Disease (COPD) exacerbation was defined as a worsening of two or more of the following major symptoms for at least 2 consecutive days: dyspnea, sputum volume or sputum purulence OR a worsening of any 1 major symptom together with an increase in any 1 of the following minor symptoms for at least 2 consecutive days: sore throat, colds (nasal discharge and/or nasal congestion), fever without other cause, cough or wheezing. A COPD exacerbation was considered of moderate severity if treatment with systemic glucocorticosteroids or antibiotics or both was required and severe if hospitalization was required. An emergency room (ER) visit of longer than 24 hours was considered a hospitalization. Rate of moderate or severe exacerbations per year = total number of moderate or severe exacerbations / total number of treatment years
Secondary Outcomes
- Rate of Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations in QVA149 and Open-label Tiotropium Treatment Arms During the Treatment Period.(76 weeks)
- Time to First Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Between QVA149, NVA237 and Open Label Tiotropium During the Treatment Period(64 weeks)
- Rate of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Requiring the Use of Both Systemic Glucocorticosteroids and Antibiotics(64 weeks)
- Number of Days With Moderate or Severe Exacerbation That Required Treatment With Systemic Corticosteroids and Antibiotics(64 weeks)
- Time to Study Withdrawal or Premature Discontinuation for Any Reason Between QVA149 (110/50 µg q.d.), NVA237 (50 µg q.d.) and Open Label Tiotropium (18 µg q.d.) During the Treatment Period.(64 weeks)
- Percentage of Patients With Study Withdrawal or Premature Discontinuation for Any Reason Between QVA149 (110/50 µg q.d.), NVA237 (50 µg q.d.) and Open Label Tiotropium (18 µg q.d.)During the Treatment Period(64 weeks)
- Cumulative Rates of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations for Multiple COPD Exacerbation at Different Time Points(26, 52, 64, 76 weeks)
- Pre-dose Forced Expiratory Volume in 1 Second (FEV-1) After 4, 12, 26, 38, 52 and 64 Weeks of Treatment Between QVA149, NVA237 and Open Label Tiotropium(4, 12, 26, 38, 52 and 64 weeks)
- Pre-dose Forced Vital Capacity (FVC)After 4, 12, 26, 38, 52 and 64 Weeks of Treatment Between QVA149, NVA237 and Open Label Tiotropium(4, 12, 26, 38, 52 and 64 weeks)
- Change in Mean Daily Use (Number of Puffs) of Rescue Therapy Between QVA149, NVA237 and Open Label Tiotropium From Baseling Over the 64 Week Treatment Period(Baseline (14 day run-in), 64 weeks)
- Change From Baseline of Percentage of Days Without Rescue Therapy Use Between QVA149,NVA237 and Open Label Tiotropium Over the 64 Week Treatment Period(Baseline (14 day run-in), 64 weeks)
- St. George's Respiratory Questionnaire (SGRQ) Scores Between QVA149, NVA237 and Open Label Tiotropium Over 12, 26, 38, 52 and 64 Weeks of Treatment(12, 26, 38, 52 and 64 weeks)