E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Uncontrolled asthma according to GINA 2006 definition |
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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 the test treatment BDP 250 mcg/salbutamol 100 mcg HFA pMDI fixed combination is non-inferior to BDP 250 mcg/salbutamol 100 mcg pMDI fixed combination given with the conventional CFC propellant (Clenil® Compositum 250, Chiesi Farmaceutici) in terms of Pulmonary Function (morning PEF). |
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E.2.2 | Secondary objectives of the trial |
To assess the efficacy of the two investigational study drugs on pulmonary function parameters, asthma symptoms, use of relief medications and frequency of asthma exacerbations;
To assess the safety of the two investigational study drugs as regards frequency of adverse events, laboratory parameters (potassium, glucose, 12-hour overnight cortisol/creatinine ratio), ECG (with QTc interval) and vital signs (heart rate and blood pressure) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Written informed consent obtained; - Male or female out-patients aged ≥ 18 and < 65 years; - Uncontrolled asthma defined according to the GINA 2006 “Classification of Levels of Asthma Control” (to be confirmed in the 2-weeks run-in period); - Forced expiratory volume in the first second (FEV1) ≥ 60% and < 80% of the predicted normal value; - Positive response to the reversibility test in the screening visit, defined as an increase of at least 12% (or, alternatively, of 200 mL) from pre-bronchodilator value in the measurement of FEV1 30 minutes following 4 puffs (4 x 100 µg) of inhaled salbutamol administered via pMDI; - Non-smokers or ex-smokers with a cumulative tobacco exposure less than 5 pack-years and who have stopped smoking since more than 1 year; - A co-operative attitude and ability to be trained to correctly use the pMDIs; - At the end of the 2-week run-in period, the condition of uncontrolled asthma is to be confirmed by reviewing the diary cards for run-in |
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E.4 | Principal exclusion criteria |
- Inability to carry out pulmonary function testing; - Diagnosis of Chronic Obstructive Pulmonary Disease (COPD); - History of near fatal asthma; - Evidence of severe asthma exacerbation or symptomatic infection of the airways in the previous 4 weeks; - Three or more courses of oral corticosteroids or hospitalisation due to asthma during the previous 6 months; - Patients who have been treated with an inhaled corticosteroid in the previous 4 weeks; - Patients who have been treated with nebulized, oral, intravenous or intramuscular corticosteroids in the past 8 weeks or depot injectable corticosteroids in the past 12 weeks; - Patients who have been treated with a long-acting β2-agonist (LABA) in the past 2 weeks; - Patients who have been treated with an oral β2-agonist in the past 48 hours; - Patients who have been treated with a short-acting β2-agonist (SABA) in the past 6 hours; - Patients who have been treated with nebulized bronchodilators in the past 2 weeks; - Patients who have been treated with anticholinergic medications (by any route) in the past 2 weeks; - Patients who have been treated with a xanthine derivative (by any route) in the past 4 weeks; - Patients who have been treated with an inhaled cromone or a leukotriene modifier in the past 4 weeks; - History or current evidence of heart failure, coronary artery disease, myocardial infarction, severe hypertension, cardiac arrhythmias; - Diabetes mellitus; - Percutaneous transluminal coronary angioplasty (PTCA) or coronary artery by-pass graft (CABG) during the previous six months; - Patients with an abnormal QTc interval value in the ECG test, defined as > 450 msec in males or > 470 msec in females; - Patients with a serum potassium value ≤ 3.5 mEq/L (or 3.5 mmol/L) and/or fasting serum glucose value ≥ 140 mg/dL (or 7.77 mmol/L); - Other haemodynamic relevant rhythm disturbances (including atrial flutter or atrial fibrillation with ventricular response, bradycardia (≤ 55 bpm), evidence of atrial-ventricular (AV) block on ECG of more than 1st degree; - Clinically significant or unstable concurrent diseases: uncontrolled hyperthyroidism, significant hepatic impairment, poorly controlled pulmonary (tuberculosis, active mycotic infection of the lung), gastrointestinal (e.g. active peptic ulcer), neurological or haematological autoimmune diseases; - Cancer or any chronic diseases with prognosis < 2 years; - Pregnant or lactating females or females at risk of pregnancy, i.e. those not demonstrating adequate contraception (i.e. barrier methods, intrauterine devices, hormonal treatment or sterilization); - History of alcohol or drug abuse; - Patients treated with monoamine oxidase inhibitors, tricyclic antidepressants or beta-blockers as regular use; - Allergy, sensitivity or intolerance to study drugs and/or study drug formulation ingredients; - Patients unlikely to comply with the protocol or unable to understand the nature, scope and possible consequences of the study; - Patients who received any investigational new drug within the last 12 weeks; - Patients who have been previously enrolled in this study; - At the end of the run-in period, patients will not be admitted to the treatment period in the case of an increase of FEV1 measured at the clinics at the end of the run-in period ≥ 15% in respect of the pre-bronchodilator value measured at the start of the run-in period; - Patients with asthma exacerbations during the run-in period will also be excluded from the study; - |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the present study is morning PEF (mean value of the last two weeks) daily measured by patients. |
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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 | 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) | 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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
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 | |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 9 |