E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic obstructive pulmonary disease (COPD) |
Enfermedad Pulmonar Obstructiva Crónica (EPOC) |
|
E.1.1.1 | Medical condition in easily understood language |
Chronic obstructive pulmonary disease (COPD) |
Enfermedad Pulmonar Obstructiva Crónica (EPOC) |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010952 |
E.1.2 | Term | COPD |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
|
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 tiotropium |
|
E.2.2 | Secondary objectives of the trial |
To investigate the safety and tolerability of roflumilast in COPD patients treated with tiotropium |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
· Giving written informed consent · Age >= 40 years · History of chronic obstructive pulmonary disease for at least 12 months prior to baseline visit V0 (ATS/ERS 2005) and chronic productive cough for 3 months in each of the 2 years prior to baseline visit V0 (if other causes of productive cough have been excluded) · FEV1/FVC ratio (post-bronchodilator) =< 70% · FEV1 (post-bronchodilator) between >= 40 % and =< 70 % of predicted · Fixed airway obstruction (defined as an FEV1 increase of =< 12 % or =< 200 ml after receiving 400 µg salbutamol) · Patients must be pre-treated with tiotropium for at least 3 months prior to V0. · Not suffering from any concomitant disease that might interfere with study procedures or evaluation · Former smoker (defined as: smoking cessation at least one year ago) or current smoker both with a smoking history of at least 10 pack years · Availability of a High Resolution CT scan dated a maximum of 6 months prior to study baseline visit V0 or willingness to have a High Resolution CT scan performed during baseline, alternatively a CT scan or a x-ray will be accepted |
|
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, treatment or remission of any 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, who are 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, intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases. Please note that female patients who are surgically sterilized/hysterectomized or post-menopausal for longer than 2 years are not considered as being of childbearing potential · Participation in another study (use of investigational product) within 30 days preceding the baseline visit V0 or re-entry if already enrolled in this trial · Alcohol or drug abuse · Inability to follow study procedures due to e.g. language problems, psychological disorders · Use of disallowed drugs · Suspected hypersensitivity and/or contraindication to any ingredients of the study medication (roflumilast or tiotropium) or rescue medication |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Mean change from randomization (V2) over 24 weeks of treatment in pre-dose study medication pre-bronchodilator FEV1 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Mean change from randomization (V2) over 24 weeks of treatment in use of rescue medication Mean TDI Focal Score (i.e. change from BDI at randomization (V2)) over 24 weeks of treatment Mean change from randomization (V2) over 24 weeks of treatment in the SOBQ |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | No |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 20 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 120 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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
|
The end of the study is defined as database lock, as this is the end of clinical data collection. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |