E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate or 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 | 10003555 |
E.1.2 | Term | Asthma bronchial |
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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 demonstrate that CHF 5188, given once daily in the morning to moderate or severe asthmatic patients, maintains the bronchodilatator effect over the 24 hours interval |
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E.2.2 | Secondary objectives of the trial |
- to compare the efficacy of CHF 5188 with that of Symbycort 200/6 mcg given twice daily (TDD 400/12 mcg) - to monitor safey 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. Male or female patients aged > or = 18 years 3. Patients with moderate or severe asthma not optimally controlled according to the GINA 2005 classification of asthma severity by daily medication regimen and response to treatment 4. Patients already treated with inhaled cortiscosteroids at stable dose for at least 4 weeks prior to inclusion 5. Patients with Forced Expiratory Volume in the first second (FEV1) ≥ 50% and ≤ 90% of predicted for the patient normal value and not less than 0.9 L in absolute value 6. Patients with a documented positive response to the reversibility test, defined as an increase of at least 12% and at least 200 mL from pre-dosing values in the measurement of FEV1 within 30 minutes after the inhalation of 400 µg salbutamol pMDI 7. Patients with a co-operative attitude and ability to be trained to correctly use the pMDI and the Turbuhaler®. |
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E.4 | Principal exclusion criteria |
Patients will not be enrolled at Visit 1 into the run-in period if they meet any of the following criteria: 1. Inability to carry out pulmonary function testing; 2. Diagnosis of COPD as defined by the current GOLD guidelines; 3. Current smokers or ex-smokers with total cumulative exposure equal or more than 5 pack-years and/or having stopped smoking one year or less prior to study start; 4. History of near fatal asthma or of a past hospitalisation for asthma in ICU; 5. Evidence of severe asthma exacerbation or symptomatic infection of the airways in the previous 4 weeks (e.g. oral corticosteroids intake); 6. Patients presenting with 3 or more asthma exacerbations in the previous year; 7. Hospitalisation due to asthma during the previous 8 weeks; 8. History of significant seasonal variation of asthma; 9. Patients treated with oral or intravenous corticosteroids in the past 4 weeks or depot injectable corticosteroids in the past 8 weeks; 10.Patients had used any of the following medications prior to screening and has not met the specified minimum wash-out period: -short-acting β2-agonists : 6 hours, -long-acting β2-agonists : 1 week, -short-acting anticholinergics : 12 hours, -long-acting anticholinergics (i.e. tiotropium bromide): 1 week, -leukotriene modifiers : 4 weeks, -fixed combinations of an anti-cholinergic and short-acting β2 agonist (e.g. Duovent® and Berodual®) :12 hours, -fixed combinations of an inhaled corticosteroid and long-acting β2-agonist (e.g. Seretide®, Symbicort®) : 1 week, -oral or nebulised bronchodilators : 4 weeks, -nebulised corticosteroids : 4 weeks, -xanthine derivative (e.g. theophylline) any formulation: 4 weeks, -sodium cromoglycate or nedocromil sodium : 4 weeks; 11. Patients with a history or current evidence of heart failure, coronary artery disease, myocardial infarction, severe uncontrolled hypertension, cardiac arrhythmias or any other significant cardiovascular disease; 12. Patients presenting with a clinically significant abnormality at a 12-lead ECG or presenting a QTcB interval in ECG > 450msec (males) or > 470msec (females); 13. Patients presenting with serum potassium < 3.5 mmol/L or > 6.0mmol/L; 14. Patients presenting with fasting serum glucose > 8 mmol/L; 15. Patients with a clinically significant or uncontrolled concomitant disease: e.g. uncontrolled hyperthyroidism, uncontrolled diabetes mellitus or other endocrine disease; significant hepatic impairment; significant pulmonary disease (e.g. tuberculosis, lung cancer or other), gastrointestinal disease (e.g. active peptic ulcer or other), neurological disease, haematological disease, autoimmune disorders or other; 16. Patients with active cancer or a history of cancer with less than 5 years disease free survival time or any other chronic disease with poor prognosis and /or affecting patient status; 17. Pregnant or lactating females or females at risk of pregnancy, i.e. those not making use of an effective contraceptive method (oral contraception, IUD, double barrier method (spermicide + condoms or spermicide + diaphragm), tubal ligature). A pregnancy test will be performed at screening in women of childbearing potential; 18. Post-menopausal female not having amenorrhoea for at least 1 year; 19. Patients with a history of alcohol or drug abuse; 20. Patients with a known intolerance/hypersensitivity to beta2-aderenergic agonists, propellant gases/excipients; 21. Patients unlikely to comply with the protocol or unable to understand the nature, scope and possible consequences of the study; 22. Patients who received any investigational new drug within the last 8 weeks
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E.5 End points |
E.5.1 | Primary end point(s) |
- Through FEV1 (mean 23h-24h FEV1) |
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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 | No |
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 | 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 | 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 | Yes |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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
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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 | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 6 |