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 | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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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 characterise the mean trough 23-24 hrs FEV1 following 4 weeks of treatment (Visit 6/Day 28) of CHF 4226 2µg given q.d. in the evening and to compare it with placebo. |
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E.2.2 | Secondary objectives of the trial |
- to compare the mean trough 23-24h FEV1 observed with CHF 4226 2 mcg q.d. with the one observed with formoterol 12 mcg bid after 4 weeks of dosing; - to compare the average (AUC standardised for time) FEV1, FVC, FEF25-75 0-3h post evening dose administration and the peak FEV1, FVC, FEF25-75 observed with CHF 4226 with the one observed with placebo and formoterol after the first dose, 1 day, 7 days, 14 days and 4 weeks of dosing; - to compare the mean trough FEV1, FVC, FEF25-75 observed with CHF 4226 with the one observed with placebo and formoterol after 1 day, 7 days, 14 days and 4 weeks of dosing; - to compare the average FEV1, FVC, FEF25-75 12-24h observed with CHF 4226 with the one observed with placebo and formoterol following the last dosing of test treatments on the evening of day 28; - to characterise FEV1, FVC, FEF25-75 following the last dose at 1, 2, 3 hrs and at 12, 13, 15, 15, 16, 18, 20, 22, 23, 24 time points; - to monitor for safety and tolerability. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients will be enrolled at Visit 1 into the run-in period if they meet all the following criteria: Written informed consent obtained; Male or female patients aged 15 years and over; Moderate or severe persistent asthma according to the GINA 2005 “Classification of Asthma Severity by Daily Medication Regimen and Response to Treatment”; Patients free of long-acting ß2 agonists treatment (LABAs) at least for 4 weeks before the screening visit and already treated for at least 1 month with inhaled corticosteroids at a stable dose corresponding to mild-medium asthma severity (GINA 2005) (up to 1000 µg BDP CFC or equivalent); Level of asthma control on existing therapy, defined as presence of day-time asthma symptoms > once a week and nocturnal asthma symptoms > twice a month. These findings are to be based on recent medical history and are to be confirmed at the end of the run-in period; Forced expiratory volume in the first second (FEV1) less or equal to 90% of predicted for the patient normal value and not less than 0.9 L in absolute value; Positive response to the reversibility test in the screening visit, defined as an increase of at least 12% and at least 250 mL from pre-dosing value in the measurement of FEV1 30 minutes following 2 puffs (2 x 100 µg) of inhaled salbutamol pMDI; Non-smokers or ex-smokers < 5 pack-year [e.g. less than 1 pack cigarettes (i.e. 20 cigarettes) per day for 5 years or 2 packs cigarettes per day for 2.5 years] and having stopped smoking > 1 year; A co-operative attitude and ability to be trained to correctly use the pMDI and the Aerolizer® inhaler; At the end of the run-in period, the presence of day-time asthma symptoms > once a week (but not every day) and nocturnal asthma symptoms > twice a month is to be confirmed by means of patient interview by the investigator. |
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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: Inability to carry out pulmonary function testing; Diagnosis of COPD as defined by the current GOLD guidelines; Current smoker or ex-smoker with total cumulative exposure equal or more than 5 pack-years and/or having stopped smoking one year or less prior to study start; History of near fatal asthma or of a past hospitalisation for asthma in an intensive care unit; History of significant seasonal variation of asthma; Evidence of severe asthma exacerbation or symptomatic infection of the airways in the previous 4 weeks (e.g. oral corticosteroids intake); Hospitalisation due to asthma during the previous 8 weeks; Patients treated with oral or intravenous corticosteroids in the past 4 weeks or depot injectable corticosteroids in the past 8 weeks; Patients treated with short-acting β2-agonists in the past 8 hours, short-acting anticholinergics in the past 12 hours, long-acting anticholinergics (i.e. tiotropium bromide) in the past 48 hours, leukotriene modifiers in the past 2 weeks; Patients treated with oral or nebulized bronchodilators in the 4 weeks prior to study start; Patients treated with nebulized corticosteroids in the 4 weeks prior to study start; Patients who have changed their dose or formulation of inhaled or nasal corticosteroids during the previous 4 weeks; Patients treated with fixed combination of inhaled corticosteroids and β2-agonists (e.g. Seretide®, Symbicort®) during the previous 4 weeks prior to study start; Patients undergoing immunotherapy; Patients treated with a xanthine derivative (e.g. theophylline) any formulation in the 4 weeks prior to study start; Patients treated with sodium cromoglycate or nedocromil sodium in the 4 weeks prior to study start; History or current evidence of heart failure, coronary artery disease, myocardial infarction, severe uncontrolled hypertension, cardiac arrhythmias or any other significant cardiac disease; Patients with a QTc interval (Bazett’s formula) in the ECG test > 450 msec in males or > 470 msec in females; Serum potassium < 3.5 mmol/L or > 6.0mmol/L; Clinically significant or unstable concurrent disease, e.g. uncontrolled diabetes mellitus; uncontrolled hyperthyroidism, significant hepatic impairment, significant pulmonary disease other than asthma (e.g. tuberculosis, lung cancer), gastrointestinal disease (e.g. active peptic ulcer), neurological or haematological autoimmune disorders; Cancer or any other chronic disease with poor prognosis and/or affecting patient status; Pregnant or lactating females or females at risk of pregnancy, i.e. those not making use of an effective contraceptive method (oral contraception, IUD, tubal ligature, double barrier method). A pregnancy test will be performed at screening in women of childbearing potential; History of alcohol or drug abuse; Patients treated with monoamine oxidase inhibitors, tricyclic antidepressants or beta-blockers; Allergy, sensitivity or intolerance to beta2-adrenergic agonists 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 8 weeks. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Trough FEV1 (L) (mean of 23 and 24 hours) at Day 28 (Visit 6) after 4 weeks of dosing. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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 | Yes |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 4 |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |
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 | 5 |