E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
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 demonstrate the non-inferiority in terms of bronchodilator effect of single administration of CHF 1535 50/6 pMDI (fixed combination of extrafine beclomethasone dipropionate 50 µg + formoterol fumarate 6 µg/metered dose, 2 inhalations, total dose 100/12 µg) given with spacer vs. free combination of extrafine beclomethasone dipropionate 50 µg/metered dose pMDI (2 inhalations, total dose 100 µg) given with spacer plus formoterol 6 µg/metered dose pMDI (2 inhalations, total dose 12 µg) given with spacer in terms of FEV1 AUC 0-12 hours corrected by time for the 12 hours study period in asthmatic children |
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E.2.2 | Secondary objectives of the trial |
-to compare the effect of the fixed combination CHF 1535 (total dose: BDP 100 µg / FF 12 µg) and of the free combination, both given with spacer, over placebo;
-to explore the dose-related efficacy of the fixed combination CHF 1535;
-to evaluate the safety profile of the study treatments
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Written informed consent obtained from the parents/legal representatives and/or the subject (if and when appropriate)
2.Prepuberal male and female outpatients, aged ≥ 5 and < 12 years (Tanner stage I and II)
3.Clinical diagnosis of asthma according to Global Strategy for Asthma Management and Prevention (GINA) revised version 2009 at least six months prior to screening visit.
4.Already treated with inhaled beclomethasone dipropionate up to 400 µg or equivalent at stable dose for at least 4 weeks prior to screening visit and inhaled short acting β2-agonists on an as needed basis.
5.Forced Expiratory Volume during the first second (FEV1) ≥ 60% and ≤ 95% of predicted normal values at the screening visit.
6.A documented positive response to the reversibility test at the screening visit, defined as ΔFEV1 ≥ 12% over baseline, 15 minutes after 200 μg salbutamol pMDI (ATS/ERS taskforce 2005).
7.A cooperative attitude and ability to use a pMDI and a spacer (AeroChamber Plus™).
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E.4 | Principal exclusion criteria |
1.Endocrinological diseases or other chronic diseases.
2.Known sensitivity to the components of study medication.
3.Any concomitant disease requiring additional treatment with topic or systemic glucocorticosteroids.
4.Allergy to one component of medications used.
5.Intolerance or contra-indication to treatment with 2-agonists and/or inhaled corticosteroids.
6.Having received an investigational drug within 2 months before the current study.
7.Inability to comply to study procedures or to study treatment intake.
8.Occurrence of acute asthma exacerbations or respiratory tract infections in the 4 weeks preceding the screening visit.
9.Significant seasonal variation in asthma or asthma occurring only during episodic exposure to an allergen or a chemical sensitizer.
10.History of cystic fibrosis, bronchiectasis or alpha-1 antitrypsin deficiency.
11.History of near fatal asthma (e.g. brittle asthma, hospitalisation for asthma exacerbation in Intensive Care Unit).
12.Diagnosis of restrictive lung disease.
13.Significant medical history and/or treatments for cardiac, renal, neurological, hepatic, endocrine diseases, or any laboratory abnormality indicative of a significant underlying condition, that may interfere with patient’s safety, compliance, or study evaluations, according to the investigator’s opinion.
14.QTc interval (Fridericia’s formula) higher than 450 msec at screening visit
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E.5 End points |
E.5.1 | Primary end point(s) |
FEV1 AUC corrected by time measured over 12 hours (15 min pre-dose and 10 min, 30 min, 1, 2, 4, 6, 8, 10, 12 hours post-dose) following the morning dose of study medication |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
-Peak FEV1
-FEV1 at 12h post-dose
-Adverse events and adverse drug reactions.
-Heart rate, systolic and diastolic blood pressure in sitting position, pre-dose and 30 min post-dose at each treatment visit.
-12-lead ECG (including QTc interval corrected by Fridericia’s formula), 15 min pre-dose and 30 min, 1, 2, 6, 12 hours post-dose
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
V2(W1),V3(W2),V4(W3),V5(W4),V6(W5) |
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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) | 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.8.2.4 | Number of treatment arms in the trial | 5 |
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 | No |
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 | No |
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 | Yes |
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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The end of the trial is defined as the last follow-up of the last subject on the trial, as the follow-up by phone is the last contact with the patient for the study.
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |