Primary objective: To demonstrate the superiority of QVA 110/50 µg compared to both QAB149 150 µg and NVA237 50 µg in terms of trough FEV1 (mean of 23 h 15 min and 23 h 45 min post-dose) following 26 weeks of treatment in patients with moderate to…
ID
Source
Brief title
Condition
- Respiratory disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Trough FEV1 after 26 weeks.
Secondary outcome
Breathlessness, quality of life, use of rescue medication.
Background summary
Morbidity and mortality caused by COPD is increasing. COPD leads to a
progressive and irreversible decrease of pulmonary function and to
exacerbations (more symptoms, decreased pulmonary function, decrease in quality
of life and increased risk of complications), which increase in frequency when
disease progresses.
Long-acting beta agonists combined with corticosteroids or long-acting
muscarinic antagonists reduce the rate of COPD exacerbations. They are
effective as monotherapy in providing long-term bronchodilation.
QVA149 is a fixed dose combination of a long-acting beta agonists (indacaterol)
and a long-acting muscarinic antagonists (glycopyrronium bromide - NVA237).
In the current placebocontrolled study, the efficacy of the combination QVA149
is compared to that of each of its components. The long-acting muscarinic
antagonist tiotropium, the golden standard at the time, serves as positive
control. This is one of the studies designed to show that the combination has
advantages in comparison with the individual components in patients with
moderate to severe COPD.
Study objective
Primary objective: To demonstrate the superiority of QVA 110/50 µg compared to
both QAB149 150 µg and NVA237 50 µg in terms of trough FEV1 (mean of 23 h 15
min and 23 h 45 min post-dose) following 26 weeks of treatment in patients with
moderate to severe COPD.
Secondary objectives: level of breathlessness using the Transitional Dyspnea
Index, quality of life using the St. George*s Respiratory Questionnaire, rescue
medication use.
Study design
Randomized double blind placebo controlled parallel group phase III study.
Double blind comparison QVA149-NVA237-indacaterol-placebo. Unblinded comparison
with tiotropium. Pre-screening, s.n. adjustment current COPD medication,
followed by 2nd screening and 2 week run-in period. Thereafter randomisation
(2:2:2:2:1) to treatment of 26 weeks with:
6. QVA149 110/50 mcg o.d.
7. NVA237 50 mcg o.d.
8. Indacaterol 150 mcg o.d.
9. tiotropium 18 mcg o.d
10. placebo.
via dry powder inhaler.
Salbutamol rescue medication.
Total study duration approx. * year.
Approx. 2100 patients.
Intervention
Treatment with QVA149, NVA237, indacaterol, tiotropium or placebo.
Study burden and risks
Risk: Adverse effects of study medication. Changes in current COPD medication.
Belasting: 14 visits in approx. * year.
Daily electronic diary (signs, symptoms, rescue medication). Vital signs 6x,
physical exam 3x, blood tests (safety) 3x (ca. 10 ml blood/visit, total amount
ca. 30 ml), pregnancy test 2x, 3x ECG, 3x COPD questionnaire.
1x pulmonary function test with reversibility. Multiple pulmonary function
tests during visits 3-13: 3x 3 in * h, 4x 5 in 2 h, 1x 5 in 2 h, 3x 11 in 5* h.
Optional: pharmacogenetic research (1x 10 ml blood), PK sampling (5 blood
samples of 3 ml in 4* h during pulmonary function tests), longer lasting
pulmonary function tests (normal 5* h, now 1x 12 and 1x 24 h, so 1x incl.
overnight stay, hotel).
Raapopseweg 1
6834 DP Arnhem
NL
Raapopseweg 1
6834 DP Arnhem
NL
Listed location countries
Age
Inclusion criteria
• Male or female adults aged >=40 years.
• Patients with moderate to severe COPD (Stage II or III) according to the (GOLD Guidelines, 2008).
• Current or ex-smokers who have a smoking history of at least 10 pack years.
• Patients with a post-bronchodilator FEV1 30-80% of the predicted normal value
• Postbronchodilator FEV1/FVC < 0.70.
• Symptomatic patients (run-in period).
Exclusion criteria
• Longterm oxygen therapy.
• Patients who have had a COPD exacerbation in the 6 weeks prior to Visit 1. Patients who develop a COPD exacerbation during a period between Visit 1 and 3 will not be eligible but will be permitted to be re-screened after a minimum of 6 weeks after the resolution of the COPD exacerbation.
• Patients who have had a respiratory tract infection within 4 weeks prior to Visit 1. Patients who develop an upper or lower respiratory tract infection during the screening period (up to Visit 3 (Day 1) will not be eligible, but will be permitted to be re-screened 4 weeks after the resolution of the respiratory tract infection.
• Other pulmonary diseases, incl. bronchial asthma (see protocol for details).
• Type I and uncontrolled type II diabetes.
• α 1-antitrypsin deficiency.
• Contra-indications for longacting beta2 agonists and/or anticholinergics.
• Use of certain COPD and other medications (see protocol for details).
• Vaccination with live or inactivated vaccines in the past 30 and 2 days resp.
• Pregnancy and breast feeding. Inadequate contraception, if relevant.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | clinicaltrials.gov registratienummer n.n.b. |
| EudraCT | EUCTR2009-017772-25-NL |
| CCMO | NL34327.060.10 |