Clinical Pharmacology Study of CHF1535 pMDI 50/6 µg Versus The Free Combination In Asthmatic Children 5-11 Years Old

Study Overview
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Brief Summary
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The rationale is to investigate the systemic availability of BDP/B17MP and formoterol after single oral inhalation of CHF 1535 50/6 pMDI vs the free combination of approved BDP and Formoterol pMDIs, in asthmatic children (5 to 11 years old).

Official Title
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A Single-dose, Open-Label, 2-Way Cross-Over, Clinical Pharmacology Study Of Chf 1535 50/6 HFA pMDI (Fixed Combination Of Beclomethasone Dipropionate 50µg Plus Formoterol Fumarate 6 µg) Using The Aerochamber Plus™ Spacer Device Versus The Free Combination Of Beclomethasone HFA pMDI And Formoterol HFA pMDI Available On The Market Using The Aerochamber Plus™ Spacer Device In Asthmatic Children

Conditions
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Asthma

Intervention / Treatment
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* Drug: CHF1535 pMDI + AC Plus
* Drug: BDP + AC Plus
* Drug: Formoterol + AC Plus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male/Female children aged 5-11 years Written informed consent obtained by parents/legal representative (according to local regulation) and by the minor (age and local regulation permitting). children with stable asthma on regular treatment with ICS or using short-acting inhaled beta2-agonists as reliever to control asthma symptoms Forced expiratory volume in one second (FEV1) > 70% of predicted values (% pred) after withholding beta2-agonist treatment for a minimum of 4 h prior to each dose period. 6. A cooperative attitude and ability to be trained about the proper use of pMDI with a spacer device and compliant to study procedures. Exclusion Criteria: Past or present diagnoses of cardiovascular, renal or liver disease Known hypersensitivity to the active treatments Exacerbation of asthma symptoms within the previous 4 weeks Inability to perform the required breathing technique and blood sampling Hospitalization due to exacerbation of asthma within 1 month prior to inclusion Lower respiratory tract infection within 1 month prior to inclusion Disease (other than asthma) which might influence the outcome of the study Obesity, i.e. > 97% weight percentile by local standards

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CHF1535 pMDI + AC Plus<br>Fixed combination of Beclomethasone Dipropionate and Formoterol 50/6 mcg with Aerochamber Plus spacer device | Drug: CHF1535 pMDI + AC Plus<br>* Four inhalations for a total dose of BDP/FF 200/24 mcg<br>* Other names: Fixed combination of BDP and FF 50/6 mcg;|
| Active Comparator: BDP and Formoterol + AC Plus<br>Beclomethasone Dipropionate 50 mcg and Formoterol 6 mcg with Aerochamber Plus spacer device | Drug: BDP + AC Plus<br>* Four inhalations for a total dose of BDP 200 mcg<br>* Other names: Beclomethasone Dipropionate 50 mcg with Aerochamber Plus;Drug: Formoterol + AC Plus<br>* Four inhalations for a total dose of Formoterol 24 mcg<br>* Other names: Formoterol 6 mcg with Aerochamebr Plus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| B17MP AUC0-t | B17MP (active metabolite of BDP) systemic exposure as AUC0-t | pre-dose until 8hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| B17MP PK profile |  | pre-dose until 8 hours post-dose | 
| BDP PK prolile |  | Pre-dose until 8 hours post-dose | 
| Formoterol PK profile |  | Pre-dose until 8 hours post-dose | 
| Plasma potassium AUC, Cmin, tmin | Plasma potassium to evaluate drug systemic effect | Pre-dose until 8 hours post-dose | 
| Urinary Cortisol excretion | 8h urinary excretion of cortisol and 8h urinary excretion of cortisol normalized for 8h creatinine excretion to evaluate dru systemic effects | Pre-dose until 8 hours post-dose | 
| Glucose in urine | Glucose to evaluate the drug systemic effects | Pre-dose until 8 hours post-dose | 
| Heart rate Time averaged heart rate value (AUC0-t)/t | Heart rate to evaluate the drug systemic effects | Pre-dose until 8 hours post-dose | 
| Spirometry: PEF | Peak respiratory flow as a measure of drug efficacy | Pre-dose until 8 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, ICS+LABA, Children, Inhalation, pMDI