* To investigate the effect of roflumilast 500 µg tablets once daily versus placebo on exacerbation rate, and pulmonary function and major adverse cardiovascular events (MACE) in COPD patients who are concomitantly treated with a fixed combination…
ID
Source
Brief title
Condition
- Respiratory disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint:
Rate of moderate or severe COPD exacerbations per patient per year. Moderate
exacerbations are defined as requiring oral or parental glucocorticosteroids,
severe as requiring hospitalisation and/or leading to death.
Secondary outcome
Key-secondary endpoints:
- Change from randomisation (V2) over 52 weeks of treatment in
post-bronchodilator FEV1.
- Rate of severe COPD exacerbations per patient per year.
Other secondary endpoints are described in protocol section 11.
Background summary
Roflumilast (DAXAS®) was approved in the European Union for the maintenance
treatment of sever COPD associated with chronic bronchitis in adult patients
with a history of frequent exacerbations as add on to bronchodilator treatment.
The use of fixed combinations of LABAs and ICS is recommended by international
COPD treatment guidelines. Roflumilast was shown to be effective and safe when
combined with either LABA or ICS. However, no trials have been performed so far
to demonstrate benefits of roflumilast when added on to fixed combinations of
LABA and ICS, which will be investigated in this trial.
Study objective
* To investigate the effect of roflumilast 500 µg tablets once daily versus
placebo on exacerbation rate, and pulmonary function and major adverse
cardiovascular events (MACE) in COPD patients who are concomitantly treated
with a fixed combination of long-acting β2-agonists (LABA) and inhaled
glucocorticosteroids (ICS)
* To obtain data on safety and tolerability of roflumilast in COPD patients
concomitantly treated with a fixed combination of LABA and ICS.
* To further characterise the population pharmacokinetic profile of roflumilast
and roflumilast N-oxide.
* To further characterise the pharmacokinetics/pharmacoynamics (PK/PD)
relationship of roflumilast, roflumilast N-oxide and 'total phosphodiesterase 4
inhibitory' activity (tPDE4i) in terms of efficacy and relevant safety aspects.
Study design
Phase III / IV, randomised, double-blind, placebo controlled study.
Intervention
Roflumilast 500 µg tablets, once daily or placebo tablets, once daily.
Study burden and risks
Roflumilast can have the following side-effects:
Common (less than 10%): Weigh decrease, decreased appetite, sleeplessness,
headache, diarrhoea, nausea, stomach ache.
Uncommon (less than 1%) : Hypersensitivity, feeling anxious, trembling,
sensation of spinning head (vertigo), dizziness, sensation of rapid or
irregular heartbeat (palpitations), gastritis, vomiting, reflux of stomach acid
to the gullet (acid regurgitations), indigestion, rash, muscle pain or cramps,
back pain, feeling of weakness or tiredness, feeling unwell.
Rare (less than 0.1%): Male breast enlargement, feeling nervous or depressed,
decreased sense of taste, respiratory tract infections (excluding pneumonia),
bloody stools, constipation, elevation of liver or muscle enzymes in blood
tests, wheals (urticaria).
Procedures when completing the entire research:
2 x Chest X-ray or CT-scan, if not performed within the last 3 months
1 x MRC dyspnoe scale
1 x HADS questionnaire
9 x questionnaire COPD assessment
2 x physical exam
2 x lenght
9 x weight
10 x pulmonary function test
2 x ECG
Langebjerg 1
Roskilde 4000
DK
Langebjerg 1
Roskilde 4000
DK
Listed location countries
Age
Inclusion criteria
2. History of COPD (according to GOLD 2009) for at least 12 months prior to baseline Visit V0 associated with chronic productive cough for 3 months in each of the 2 years prior to baseline Visit V0 (with other causes of productive cough excluded).
3. Age >= 40 years
4. Forced expiratory volume after one second (FEV1) / forced vital capacity (FVC) ratio (post-bronchodilator) < 70%
5. FEV1 (post-bronchodilator) <= 50% of predicted
6. At least two documented moderate or severe COPD exacerbations, separated by at least 10 days, within one year prior to baseline visit V0.
7. Patients must be pre-treated with LABA and ICS for at least 12 months before baseline Visit V0. Up to 3 months before baseline Visit V0 free or fixed combinations of LABA and ICS are allowed, including changes in dose, active substances, and brands. In the last 3 months before baseline Visit V0 patients must be pre-treated with fixed combinations of LABA and ICS at a constant dose (maximum approved dosage strength of the combination)
8. Former smoker (defined as smoking cessation at least one year ago) or current smoker both with a smoking history of at least 20 pack years.
Exclusion criteria
1. Moderate or severe COPD exacerbations and/or COPD exacerbations treated with antibiotics ongoing at the baseline visit V0
2. Lower respiratory tract infection not resolved 4 weeks prior to the baseline visit V0
3. Diagnosis of asthma and/or other relevant lung disease
4. Current participation in a pulmonary rehabilitation program or completion of a pulmonary rehabilitation program within 3 months preceding the baseline visit V0. However, physical exercise maintenance following the completion of the initial pulmonary rehabilitation program and which is continuously performed within 3 months preceding baseline Visit V0 and during the complete trial is allowed.
5.Known alpha-1-antitrypsin deficiency.;Exclusion criteria within ethical considerations in terms of general health are listed in the protocol, section 6.2.2.
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 |
|---|---|
| EudraCT | EUCTR2010-019685-87-NL |
| ClinicalTrials.gov | NCT01329029 |
| CCMO | NL35334.094.11 |