E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with moderate to severe persistent asthma. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049106 |
E.1.2 | Term | Asthma chronic |
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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 therapeutic efficacy in a non-inferiority model of 12 weeks course of SMB BUDESONIDE-SALMETEROL DPI capsule 150/25μg delivered by AXAHALER®, taken BID, versus SYMBICORT® TURBUHALER® 200/12μg BID, taken by inhalation, in patients with moderate to severe persistent asthma.
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E.2.2 | Secondary objectives of the trial |
- To compare the safety of SMB BUDESONIDE-SALMETEROL DPI capsule 150/25μg taken BID versus SYMBICORT® TURBUHALER® 200/12μg BID taken by inhalation, in patients with moderate to severe persistent asthma over 12 weeks. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients must satisfy the following criteria before entering the study: - Male or female, aged between 18 and 65 years of age inclusive; - History of moderate to severe persistent asthma for at least 6 months prior to the screening visit; - Reversibility of at least 12% in FEV1 and 200 ml following inhalation of 400μg salbutamol at screening; - FEV1 more than or equal to 50% (upper limit 80%) of predicted at screening and baseline (prior to dosing with study medication); - Already treated with ICS at a stable daily dose < or = 1000 μg beclomethasone dipropionate-equivalent (estimated according to GINA guidelines) for at least 4 weeks prior to the screening visit and having asthma symptoms partly controlled or uncontrolled; - Able to comply with all study procedures, including the use of study inhalers, spirometer and peak flow meter; - Willing to withhold the use of short acting β-agonists for at least 6 hours prior to each clinic visit; - Provide written, informed consent to participate in the study, indicated by a personal signature and date on the patient consent form; - If the patient is a female and of childbearing potential, she must be using an efficient means of birth control, as determined by the investigator and provide a negative urine dipstick pregnancy test (to be confirmed by a blood test) at the screening visit and a negative urine dipstick pregnancy test at the randomization visit.
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E.4 | Principal exclusion criteria |
- Severe life-threatening asthma or hospitalization for an asthma exacerbation within 3 months prior to the screening visit and hospitalization for a related disorder (pneumothorax, bronchopneumonia, etc.) in the past 3 months before screening visit; - Evidence of any unstable or untreated clinically significant immunological, neoplastic, endocrine, haematological, hepatic, renal, gastrointestinal, neurological or psychiatric abnormalities or medical disease; - Presence or history of any significant cardiac arrhythmia or diagnosed cardiac disease including coronary artery disease, congestive heart failure and uncontrolled hypertension; - Respiratory tract infection requiring treatment with antibiotics within 8 weeks prior to the screening visit; - Any significant respiratory disorder other than asthma; - Smokers of more than 10 cigarettes/day (or equivalent) or a smoking history of more than 10 pack years; - Pure seasonal asthma and/or a history of seasonal exacerbation of asthma; - Use of any of the prohibited medication as detailed in the concomitant medication section; - Participation in any other clinical trial within 2 months of the screening visit; - Presence of any other condition or illness, which, in the opinion of the investigator would interfere with optimal participation in the study; - Patients with any sensitivity or allergy to any of the products used within this clinical trial; - Patients with diabetes mellitus; - History of drug and/or alcohol abuse; - Incompliance to PEF tests and study medication (more than 20% of PEF tests or study medication intake missing) during the run-in period; - Patients with asthma exacerbations during the run-in period; - Patients with known history of hepatitis and/or AIDS or patients with positive virology laboratory tests (HBsAg, HCV Ab, HIV 1+2 Ab)
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy variable: - Mean change over the weeks from baseline to the final visit (week 12) in the morning pre-dose PEF
Secondary efficacy variables (PFT will be performed at each visit before study drug intake at least 12h after the previous dose) :
- Mean Change over the weeks from baseline to week 12 in evening pre-dose PEF - Mean Change over the weeks from baseline to week 12 in FEV1 - Mean Change over the weeks from baseline to week 12 in FEV1% of predicted - Mean Change over the weeks from baseline to week 12 in FVC - Asthma symptoms score (mean change over the weeks from baseline to week 12) - Sleep disturbance score (subset of the asthma symptom score) (mean change over the weeks from baseline to week 12) - Number of asthma exacerbations - Number of bronchodilator rescue inhalations
Safety profile will be compared using: Adverse events, Physical examination, Vital signs, 12-lead ECG, Laboratory data, Withdrawals or drop-out rate due to Adverse Events .
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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 | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
open with randomized treatment assignment |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 | 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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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 | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |