E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 10003553 |
E.1.2 | Term | Asthma |
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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 evaluate the effect of BDP and Formoterol administered as extrafine fixed combination pMDI (Foster®), in comparison with the fixed combination of Budesonide and Formoterol (Symbicort Turbohaler), on small airways, by measuring alveolar nitric oxide and lung resistance in asthmatic patients. |
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E.2.2 | Secondary objectives of the trial |
• to evaluate the lung reactance (Xrs) • to compare the treatment effects on respiratory functions and nitric oxide and on inflammation biomarkers in sputum • to assess the safety and tolerability |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent obtained 2. Adult male and female (≥18 and ≤65 years) 3. Clinical diagnosis of Asthma according to Global Strategy for Asthma management and Prevention (GINA) revised version 2007 4. Patients treated with inhaled corticosteroids equivalent to Budesonide 200 µg b.i.d. (with or without LABA), including fixed combination 5. FEV1 ≥ 65% of the predicted normal value pre-bronchodilator 6. A documented positive response to the reversibility test, defined as an improvement in FEV1 of at least 12% from baseline value and 200 ml 30 minutes after 4 puffs of inhaled salbutamol pMDI (400 µg) at screening or within a year prior to screening and/or documented hyper-responsiveness to methacholine on bronchial challenge testing 7. FENO > 30 ppb at screening. If this test fails, it can be repeated once (Screening Visit 1 rescheduled within 7 days. In this case, only NO measurement will be re-performed) |
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E.4 | Principal exclusion criteria |
1. Inability to carry out pulmonary function testing and NO testing; 2. Diagnosis of COPD as defined by the current GOLD guidelines (2006); 3. History of near fatal asthma; 4. Evidence of severe asthma exacerbation or symptomatic infection of the airways in the previous 8 weeks; 5. More than two courses of oral corticosteroids or hospitalisation due to asthma during the previous 6 months; 6. Current smokers or recent (less than one year) ex-smokers defined as smoking more than 10 pack-years; 7. Clinically significant or unstable concurrent disease: e.g. uncontrolled hyperthyroidism, uncontrolled diabetes mellitus or other endocrine disease; significant hepatic impairment; significant renal impairment; significant other pulmonary disease; cardiovascular disease; gastrointestinal disease; neurological disease; haematological disease, autoimmune disorders, that may interfere with patient’s safety, compliance, or study evaluations, according to the investigator’s opinion; 8. Cancer or any chronic diseases with prognosis < 2 years; 9. Female subjects: pregnant or with active desire to be pregnant, lactating mother or lack of efficient contraception in a subject with child-bearing potential (i.e. contraceptive methods other than oral contraceptives, IUD, tubal ligature). A pregnancy test in urine is to be carried out in women of a fertile age at screening; 10. Significant alcohol consumption or drug abuse; 11. Patients treated with leukotrien modifiers, inhaled long-acting and shortacting anticholinergics, monoamine oxidase inhibitors or beta-blockers as regular use 12. Patients treated with tricyclic antidepressants or Selective Serotonin Reuptake Inhibitors (SSRIs) unless already taken at stable doses at the screening visit; 13. Patients treated with extrafine formulations of ICS or fixed combinations of ICS and LABA 14. Allergy, sensitivity or intolerance to study drugs and/or study drug formulation ingredients; 15. Patients unlikely to comply with the protocol or unable to understand the nature, scope and possible consequences of the study; 16. Patients who received any investigational new, not yet approved drugs within the last 8 weeks. |
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E.5 End points |
E.5.1 | Primary end point(s) |
After the 4-week treatment the following parameters will be evaluated:
• Alveolar NO concentration (Calv, ppb) • IOS ∆R5-R20 |
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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 | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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 | Information not present in EudraCT |
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
| |
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |