E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate persistent asthma sub optimally controlled on existing therapy. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003553 |
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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 |
Primary:
To demonstrate the non inferiority in terms of morning PEF of the "free combination" of CHF 4226 HFA pMDI + extrafine budesonide HFA pMDI given once daily in the evening (2µg + 200µg qd) versus CHF 4226 HFA pMDI + extrafine budesonide HFA pMDI given twice daily (1µg + 100µg bid).
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E.2.2 | Secondary objectives of the trial |
Secondary:
To demonstrate the superiority of both "free combination" regimens over the Inhaled CorticoSteroid [ICS] monotherapy [Budesonide Turbuhaler];
Evaluation of the other lung function endpoints (FEV1, FCV, FEF25-75), effect on asthma symptoms, rescue salbutamol use;
To monitor for safety and tolerability. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Patients will be enrolled at Visit 1 into the run-in period if they meet all of the following criteria:
Written informed consent obtained;
Male or female patients aged > or equal to 18 years;
Moderate persistent asthma according to the GINA 2004 “Classification of Asthma Severity by Daily Medication Regimen and Response to Treatment”, sub-optimally controlled on existing therapy;
Patients free of long-acting beta2 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 asthma severity (GINA 2004) (up to 500µg BDP CFC or equivalent);
Asthma not adequately controlled on existing therapy, defined as presence of asthma symptoms > once a week and nocturnal asthma symptoms > twice a month. These findings are to be confirmed at the end of the run-in period, taking into consideration the patient's recent medical history;
Forced expiratory volume in the first second (FEV1) > or equal to 60% and < 80% of predicted for the patient normal value;
Positive FEV1 reversibility test at the screening visit, defined as an increase of at least 15% and at least 200 mL from pre-dose value in FEV1 30 minutes following 4 puffs (4 x 100 µg) of inhaled salbutamol pMDI;
A documented FEV1 positive reversibility test as above, is acceptable if performed within 6 months of the screening visit ;
Non-smokers or ex-smokers with cumulative tobacco exposure < 5 pack-years [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 who have stopped smoking for at least 1 year;
A co-operative attitude and ability to be trained to correctly use the pMDI and 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 one or more of the following criteria:
Inability to carry out pulmonary function testing;
Diagnosis of COPD as defined by the current GOLD guidelines;
History of near fatal asthma;
History of significant seasonal variation of asthma;
Asthma exacerbation or symptomatic infection of the airways in the previous 4 weeks or during the run-in period (e.g. oral corticosteroids intake, antibiotics);
Patients presenting with 3 or more asthma exacerbations in the previous 6 months; Hospitalization due to asthma during the previous 8 weeks;
Patients who have been treated with oral or intravenous corticosteroids in the past 4 weeks or depot injectable corticosteroids in the past 8 weeks or during the run-in period;
Patients who have changed their dose or formulation of their inhaled corticosteroids during the previous 4 weeks or during the run-in period;
Patients who have been treated with a short-acting β2-agonist in the past 8 hours;
Patients who have been treated with an oral β2-agonist in the past 4 weeks;
Patients who have been treated with nebulized β2-agonists, nebulized corticosteroids, inhaled anticholinergics, leukotriene modifiers, xanthine derivatives (e.g. theophylline any formulation) in the past 4 weeks or during the run-in period;
Patients who have been treated with sodium cromoglycate or nedocromil sodium in the past 12 hours or during the run-in period;
Patients who have been treated with an inhaled combination drug (eg Seretide®, Symbicort®, Duovent®, Berodual®) in the past 4 weeks or during the run-in period; History or current evidence of heart failure, coronary artery disease, myocardial infarction, severe uncontrolled hypertension, cardiac arrhythmias or any other significant cardiovascular disease;
Patients with a QTc interval (Bazett’s formula) in the ECG test > 450 msec in males or > 470 msec in females;
Patients with serum potassium < 3.5mEq/L or > 6.0mEq/L;
Clinically significant or unstable 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;
Cancer or any other chronic disease with poor prognosis and /or affecting patient status;
Pregnant or lactating females or females at risk of pregnancy, who are not making use of an effective contraceptive method. A pregnancy test will be performed at screening in women of childbearing potential;
Patients who have been treated with monoamine oxidase inhibitors, tricyclic antidepressants, Selective Serotonin Re Uptake Inhibitors (SSRIs), long-acting antihistamines or beta-blockers in the past 48 hours or during the run-in period (if the patient is on a short acting antihistamine or SSRI treatment, she/he can be included in the study under the following 2 conditions : (i) a recent ECG while patient was on therapy with these medications demonstrate that the QTc interval is in normal range;(ii) these therapies are taken in an unchanged dose throughout the duration of the study);
Allergy, sensitivity or intolerance to study drug formulation or excipients;
Patients unlikely to comply with the protocol or unable to understand the nature, scope of the study but also the possible benefits or unwanted effects of the study treatments;
Patients who received any investigational new drug, or participated in a clinical study within the last 8 weeks;
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary variables:
Morning PEF (L/min) measured daily with the electronic peak flow meter (mean of at least 7 values obtained during the last 14 days of the treatment period).
Secondary variables:
Morning and evening PEF (L/min) measured with the electronic peak flow meter in the last 14 days before each clinic visit;
FEV1 (L) , FVC (L), FEF25-75 (L/s) measured at clinic at each visit; Day and night asthma symptoms scores;
Percentage of nights and / or days free of symptoms;
Salbutamol rescue use;
Asthma control.
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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 | 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 | No |
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 | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
double-dummy, open label active treatment |
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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
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 | 7 |
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 | 7 |