E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic obstructive pulmonary disease (COPD) = EPOC (Enfermedad Pulmonar Obstructiva Crónica) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | llt |
E.1.2 | Classification code | 10010952 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the effect of 500µg roflumilast versus placebo once daily in COPD patients treated with salmeterol
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E.2.2 | Secondary objectives of the trial |
To investigate the safety and tolerability of roflumilast in COPD patients treated with salmeterol
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
· Written informed consent · Age > or = 40 years · History of chronic obstructive pulmonary disease for at least 12 months prior to baseline visit V0 (ATS/ERS 2005) · FEV1/FVC ratio (post-bronchodilator) < or = 70% · FEV1 (post-bronchodilator) between > or = 40% and < or = 70% of predicted · Fixed airway obstruction (defined as an FEV1 increase of < or = 12% or < or = 200 ml after receiving 400 µg salbutamol) · Not suffering from any concomitant disease that might interfere with study procedures or evaluation · Current smoker with a smoking history of at least 10 pack years OR · Former smoker (defined as: smoking cessation at least one year ago) that has a smoking history of at least 10 pack years · Availability of a chest x-ray or CT scan dated a maximum of 6 months prior to study baseline visit V0 or willingness to have a chest x-ray performed at visit V0
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E.4 | Principal exclusion criteria |
· COPD exacerbation indicated by a treatment with systemic glucocorticosteroids and/or antibiotics not stopped at least 4 weeks prior to the baseline visit V0 · Lower respiratory tract infection not resolved 4 weeks prior to the baseline visit V0 · Diagnosis of asthma and/or other relevant lung disease (e.g. history of bronchiectasis, cystic fibrosis, bronchiolitis, lung resection, lung cancer, interstitial lung disease [e.g. fibrosis, silicosis, sarcoidosis], and active tuberculosis) · Current participation in a pulmonary rehabilitation program or completion of a pulmonary rehabilitation program within 3 months preceding the baseline visit V0 · Known alpha-1-antitrypsin deficiency · Clinically relevant abnormal laboratory values suggesting an unknown disease and requiring further clinical evaluation (as assessed by the investigator) · Known infection with HIV and/or active hepatitis · Diagnosis or history of cancer (other than basal cell carcinoma) within 5 years prior to study start · Clinically significant cardiopulmonary abnormalities (diagnosed clinically or by x-ray / CT-scan / ECG) that are not related to COPD and that require further evaluation · Pregnancy, breast feeding, oocyte donation or oocyte implantation planned during the trial · Female patients of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, unless they are surgically sterilized/hysterectomized or post-menopausal > 2 years or who are not using any other method of contraception considered sufficiently reliable by the investigator in individual cases · Participation in another study (use of investigational product) within 30 days preceding the baseline visit V0 or re-entry of patients already enrolled in this trial · Suspected inability or unwillingness to comply with study procedures · Alcohol or drug abuse · Inability to follow study procedures due to e.g. language problems, psychological disorders · Use of not allowed drugs · Suspected hypersensitivity to the study medication (roflumilast or salmeterol) or rescue medication, or any other contraindication for the use of salmeterol
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary variable · Mean change from randomization V2 in pre-dose study medication pre-bronchodilator FEV1
Secondary variables · Mean change from randomization V2 in spirometry parameters · Use of rescue medication (diary cards) and · Symptoms of cough and sputum · BDI/TDI · SOBQ · Exacerbations
Safety: · Adverse events · Changes in laboratory values · Changes in vital signs including blood pressure (BP), heart rate (HR) and electrocardiograms (ECG)
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 18 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 18 |