severe uncontrolled asthma MedDRA version: 14.0 Level: LLT Classification code 10003555 Term: Asthma bronchial System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Trade Name: Daxas
Product Name: roflumilast
Product Code: BY217
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ROFLUMILAST
CAS Number: 162401-32-3
Current Sponsor code: BY217
Concentrat
Sponsors
Nycomed GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Written informed consent. - Age 18 years or above. - Documented physician diagnosis of severe asthma consistent with the Global Initiative for Asthma (GINA) clinical features (step 4) for at least 6 months. - Treated with a fixed or free combination of at least medium-dose ICS plus LABA for at least 3 months prior to baseline period with stable treatment for at least 4 weeks before Visit (V2). - GINA-defined uncontrolled asthma or an asthma control questionnaire (ACQ-7) score = 1.5 despite at least medium dose ICS/LABA therapy within 4 weeks prior to baseline (V0). - Pre-bronchodilator forced expiratory volume in 1 second (FEV1) 40–85% of predicted at V0. For subjects participating in the sputum sub-study only: FEV1 > 55% of predicted and > 1 Litre. - Non-smokers or ex-smokers (defined as: smoking cessation at least 1 year ago) with a smoking history of =10 pack years. - Airway obstruction proven to be reversible by an improvement of FEV1 of at least 12% and 200 ml after inhalation of a short-acting bronchodilator. This can be either documented in the medical history (with supporting spirometry recordings) in the previous 12 months or demonstrated during screening. - Subjects who, with the exception of asthma, are in good health. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 110 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Severe asthma exacerbation2 not resolved 4 weeks prior to baseline visit V0. - Lower respiratory tract infection not resolved 4 weeks prior to baseline visit V0. - A diagnosis of Chronic Obstructive Pulmonary Disease (COPD) based on GOLD criteria and/or other relevant forms of lung disease (e.g. history of primary bronchiectasis, cystic fibrosis, idiopathic (pan)bronchiolitis or bronchiolitis obliterans, bronchopulmonary allergic aspergillosis, Churg-Strauss Syndrome, paradoxical vocal cord closure, lung resection, lung cancer, interstitial lung disease [e.g. fibrosis, silicosis, sarcoidosis], or active tuberculosis) that may interfere with the evaluation of a treatment response. - Current participation in a pulmonary rehabilitation program or completion of a pulmonary rehabilitation program within 3 months preceding V0. - History of clinically significant allergies or idiosyncrasies to roflumilast, or any inactive ingredient(s) of these products. - History of severe allergy to any drugs, food or beverages. - Females of childbearing potential3 not willing to use acceptable contraceptive methods such as hormonal contraceptives (oral, injection or implant) or intrauterine contraceptive devices or who started such methods less than 2 months prior to screening or who are not willing to use a double barrier method of contraception (diaphragm plus condom). - Lactating or pregnant females. A positive pregnancy test before the first administration of investigational medicinal product or breastfeeding. - Male subjects planning to father during clinical trial conduct or within 3 months after the last planned dose of trial treatment. - Planned donation of germ cells, blood, organs or bone marrow during the course of the trial. - Subjects previously enrolled in the current clinical trial (see Section 5.7 of the protocol: Replacement and re-enrolment policy for replacement and re-enrolment policy). - Suffering from concomitant disease or condition including those that might interfere with trial procedures or evaluations. - Use of disallowed drugs listed in Section 6.8.2 of the protocol: Disallowed medication.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Evaluation from visit V2 (end of baseline) and visit V4 (end of washout), to the last post-randomisation measurement of the respective treatment period;Main Objective: The main objective of the trial is to investigate the effect of 500 µg roflumilast tablets taken once-daily, versus placebo, on pulmonary function in subjects with asthma not adequately controlled with a combination of at least medium dose inhaled corticosteroids/long-acting inhaled beta2-agonist (ICS/LABA) maintenance therapy.;Primary end point(s): Change in morning pre-dose (trough) FEV1 (L) from visit V2 (end of baseline) and visit V4 (end of washout), to the last post-randomisation measurement of the respective treatment period.;Secondary Objective: Secondary objectives are to investigate the effect of 500 µg roflumilast tablets taken once-daily, versus placebo, on asthma symptoms, inflammatory markers, safety and tolerability. In addition, the effect on fractioned exhaled nitric oxide (FeNO) and on inflammatory markers in induced sputum will be investigated in selected trial centres as exploratory objectives in a sub-study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Change from visit V2 (end of baseline) and visit V4 (end of washout period) to the last post-randomisation measurement of the respective treatment period in: • Forced vital capacity (FVC [L]), forced expiratory flow 25-75% (FEF25-75% [L/s]) and peak expiratory flow (PEF [L/min]) • Morning PEF from home PEF measurements • Asthma symptoms, i.e. day- and night-time asthma symptom score • Rescue medication (salbutamol) usage • Asthma exacerbations (severity, frequencies, number of days, duration) Exploratory endpoints • Inflammatory markers in blood: o Total and differential white blood cell (WBC) counts (absolute [cells/VOL and percentage]) o Inflammatory mediators (Human InflammationMAP® v.1; Rules Based Medicine [RBM]) Further exploratory endpoints from sub-study only • Differential inflammatory cell count in induced sputum (eosinophils, neutrophils, macrophages, lymphocytes, epithelial cells) • Molecular markers of inflammation in induced sputum supernatant, including for example Interleukin (IL)- 5, IL-8, matrix metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinase (TIMP), myeloperoxidase (MPO) • Fractioned exhaled Nitric Oxide (FeNO) ;Timepoint(s) of evaluation of this end point: Evaluation from visit V2 (end of baseline) and visit V4 (end of washout period) to the last post-randomisation measurement of the respective treatment period | — |
Countries
Bulgaria, Germany, South Africa
Contacts
Public ContactSusanne Wolf
Nycomed GmbH
Outcome results
None listed