Pulmonary Function, Asthma Symptoms and Inflammatory Markers in Subjects with Severe Asthma MedDRA version: 15.1 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Trade Name: Daxas
Product Name: Roflumilast 500µg film-coated tablet
Product Code: BY217
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ROFLUMILAST
CAS Number: 162401-32-3
Current Sponso
Sponsors
Takeda Pharma A/S
Eligibility
Sex/Gender
All
Inclusion criteria
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. 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 55 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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).;Secondary Objective: 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. ;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. ;Timepoint(s) of evaluation of this end point: Day 1, Day 28, Day 56, Day 84 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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. ;Timepoint(s) of evaluation of this end point: Day 1, Day 28, Day 56, Day 84 | — |
Countries
Germany, Hungary, South Africa
Contacts
Public ContactClinical Trial Manager
Takeda Pharma A/S
Outcome results
None listed