E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pulmonary Function, Asthma Symptoms and Inflammatory Markers in Subjects with Severe Asthma |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 15.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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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 assess the effect of roflumilast 500 µg QD plus montelukast 10 mg QD versus 10 mg montelukast QD alone on pre-dose (trough) pre-bronchodilator forced expiratory volume in 1 second (FEV1). |
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E.2.2 | Secondary objectives of the trial |
To assess the effect of roflumilast 500 µg QD plus montelukast 10 mg QD versus 10 mg montelukast QD alone on further spirometry parameters, including:
• Forced Vital Capacity (FVC); expiratory, pre-bronchodilator
• Forced Expiratory Flow 25-75% (FEF 25-75), pre-bronchodilator
• Peak Expiratory Flow Rate (PEF), pre-bronchodilator
Additional Objective:
To assess the Safety and tolerability of roflumilast 500 µg QD and montelukast 10mg QD versus 10 mg montelukast QD alone.
To assess the effect of roflumilast 500 µg QD plus montelukast 10 mg QD versus montelukast 10 mg QD alone on:
• The level of Inflammatory Biomarkers in blood and induced sputum/ sputum supernatant.
• Fractioned exhaled nitric oxide.
• Short-acting Beta Agonist (SABA) use.
• Asthma Control Questionnaire (ACQ).
• Asthma Exacerbations.
• Drop-outs due to Adverse Events.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The subject has a documented physician diagnosis of severe asthma consistent with Global Initiative for Asthma (GINA 2011) step 4 clinical features for at least 6 months prior to Visit 1.
2. The subject has been treated with a fixed or free combination of at least medium-dose ICS (ie, ≥250 µg fluticasone propionate daily or equivalent ICS) plus LABA for at least 3 months prior to Baseline Visit 1 and a stable ICS dose for at least 4 weeks before Visit 2.
3. The subject shows 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 at both Visit 1 and Visit 2.
4. The subject shows a pre-bronchodilator forced expiratory volume in 1 second (FEV1) of >55% and ≤ 85% of predicted at Visit 1. For subjects performing induced sputum FEV1 must be in addition >1 liter.
5. Subject has 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 may be documented either in the medical history (with supporting spirometry recordings) in the previous 12 months or demonstrated during Screening.
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E.4 | Principal exclusion criteria |
1. Severe asthma exacerbation not resolved 4 weeks prior to Baseline Visit 1, (defined by the need for oral or parenteral glucocorticosteroid intake for at least 3 days and/or hospitalization or emergency room visit with the need for oral or parenteral corticosteroid use).
2. Lower respiratory tract infection not resolved 4 weeks prior to Baseline Visit 1.
3. A diagnosis of chronic obstructive pulmonary disease (based on GOLD criteria) and/or other relevant forms of lung disease (eg, 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 [eg, fibrosis, silicosis, sarcoidosis], or active tuberculosis) that may interfere with the evaluation of a treatment response.
4. Current participation in a pulmonary rehabilitation program or completion of a pulmonary rehabilitation program within 3 months preceding Visit 1.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from Visit 2 (end of Baseline) and Visit 4 (end of Washout Period) to the Week 4 measurement of the respective Treatment Period in pre-dose (trough) FEV1. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 1, Day 28, Day 56, Day 84 |
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E.5.2 | Secondary end point(s) |
• Change from Visit 2 (end of Baseline) and Visit 4 (end of Washout Period) to the Week 4 measurement of the respective Treatment Period in
- FVC.
- FEF25-75%.
- PEF.
• Change from Visit 2 (end of Baseline) and Visit 4 (end of Washout Period) to the Week 4 measurement of the respective Treatment Period in Morning PEF from home PEF measurements and day- and nighttime asthma symptoms.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day 1, Day 28, Day 56, Day 84 |
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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 | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Biomarkers will be investigated in an exploratory manner |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.1.6 | Cross over | Yes |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 | No |
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 | 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
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End of the trial is defined as last visit of the last subject (LVLS) + 30 days for AE follow-up. |
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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 | |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 12 |