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 | 12.0 |
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 demonstrate superiority of CHF5188 pMDI 400/4µg administered once-a-day in the morning over budesonide extrafine pMDI on trough FEV1 after 4 weeks of treatment in persistent moderate or severe asthmatic patients partly controlled with ICS or ICS/LABA. |
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E.2.2 | Secondary objectives of the trial |
- To compare the efficacy of CHF5188 given once-a-day with that of Seretide® Evohaler pMDI 50/25µg administered twice-a-day after 4 weeks of treatment - To assess the occurrence of tolerance by comparing the effect on trough and peak FEV1 after the first and the last dose of study drug - To monitor 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. Male or female patients aged ≥ 18 years; 3. Patients with moderate or severe asthma partly controlled with ICS or ICS/LABA at a stable dose for at least 8 weeks prior to inclusion, according to the GINA 2008 “Management Approach Based On Control"; 4. Patients with Forced Expiratory Volume in the first second (FEV1) ≥ 60% and ≤ 90% of predicted for the patient normal value; 5. Patients with a documented positive response to the reversibility test, defined as an increase of at least 12% and at least 250mL from pre-dosing values in the measurement of FEV1 within 30 minutes after the inhalation of 400 µg salbutamol pMDI; If the reversibility criteria are not met, the testing can be repeated once. This requirement must be met after re-testing during run-in period at least 24h prior to randomisation. 6. Patients with a co-operative attitude and ability to be trained to correctly use the pMDI.
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E.4 | Principal exclusion 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 : 24 hours, short-acting anticholinergics : 12 hours, leukotriene modifiers : 4 weeks, Fixed combinations of an anti-cholinergic and short-acting β2-agonist (e.g. Duovent® and Berodual®) :12 hours, oral or nebulised bronchodilators : 4 weeks, nebulised corticosteroids : 4 weeks, sodium cromoglycate or nedocromil sodium : 4 weeks; Patients have received live-attenuated virus vaccination within 2 weeks prior to screening (inactivated influenza vaccination is acceptable provided it is not administered 48h prior to screening) 12. 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; 13. Patients presenting with a clinically significant abnormality at a 12-lead ECG or presenting a QTcF interval in ECG > 450msec (males) or > 470msec (females); 14. Patients presenting with serum potassium < 3.5 mmol/L or > 6.0mmol/L; 15. Patients presenting with fasting blood glucose > 8 mmol/L; 16. 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; 17. 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; 18. Pregnant or lactating females or females at risk of pregnancy, i.e. those not making use of an effective contraceptive method (oral contraception, UID, double barrier method (spermicide + condoms or spermicide + diaphragm), tubal ligature). A pregnancy test will be performed at screening in women of childbearing potential; 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 4 weeks.
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E.5 End points |
E.5.1 | Primary end point(s) |
Trough FEV1 (mean 23h-24h FEV1) after day 28 dose |
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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 | 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) | 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) | 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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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 | 12 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 12 |