Clinical Pharmacology of CHF 1535 50/6 ug Next DPI in Children 5-11 Years Old

Study Overview
=================
Brief Summary
-----------------
This is a pharmacokinetic comparison of CHF 1535 50/6 NEXT DPI versus the free combination of Beclomethasone DPI and Formoterol DPI in children (5 to 11 years old) of a formulation already approved in adults.

Detailed Description
-----------------
Pharmacokinetic study in asthmatic children 5 to 11 years old treated with either a fixed combination of beclomethasone 50 ug/unit dose plus formoterol fumarate 6 ug/unit dose via the NEXT DPI dry powder inhaler or a free combination of Beclomethasone 100 ug DPI and Formoterol 6 ug DPI according to a cross-over design.

Official Title
-----------------
A Single-dose,Open-label,Randomized,2-way Cross-over,Clinical Pharmacology Study of CHF1535 50/6 NEXT DPI® Fixed Combination of Beclomethasone Dipropionate 50µg Plus Formoterol Fumarate 6µg)Versus the Free Combination of Licensed Beclomethasone DPI and Formoterol DPI in Asthmatic Children

Conditions
-----------------
Asthma in Children

Intervention / Treatment
-----------------
* Drug: free comb. beclomethasone DPI and formoterol DPI
* Drug: CHF 1535 50/6 NEXT DPI


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male/Female children aged 5 -11y 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 Children with 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-agonists treatment for a minimum of 4 h prior to each study treatment. A cooperative attitude and ability to be trained about the proper use of DPI 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 screening (visit 1) Lower respiratory tract infection within 1 month prior to screening (visit 1) 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
-----------------
Minimum Age: 5 Years
Maximum Age: 11 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: reference treatment<br>Free combination of Beclomethasone dipropionate DPI and Formoterol fumarate DPI | Drug: free comb. beclomethasone DPI and formoterol DPI<br>* free combination of beclomethasone dipropionate 100 ug/unit DPI (two inhalations, total dose 200 ug), and formoterol fumarate 6 ug/unit DPI (four inhalations, total dose 24 ug).<br>|
| Experimental: CHF 1535 NEXT DPI<br>CHF 1535 50/6 NEXT DPI | Drug: CHF 1535 50/6 NEXT DPI<br>* four inhalations of CHF 1535 50/6 NEXT DPI, a fixed combination of beclomethasone dipropionate 50 ug plus formoterol fumarate 6 ug (TOTAL DOSE:BDP/FF 200/24 ug)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| B17MP (active metabolite of BDP) Area Under Curve (AUC) | B17MP: Profile of Pharmacokinetics | predose, 15,30min, 1,2,4,6,8 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| B17MP Cmax,Tmax,T1/2 | BDP: profile of pharmacokinetics. | predose, 15min,30min,1,2,4,6,8 hours post dose | 
| BDP Area Under Curve (AUC), Cmax, Tmax, T1/2 | BDP: profile of Pharmacokinetics | predose, 15min,30min,1,2,4,6,8 hours postdose | 
| Formoterol Area Under Curve (AUC), Cmax, Tmax, T1/2 | Formoterol: profile of pharmacokinetics | predose, 15min, 30 min, 1,2,4,6,8 hours postdose | 
| plasma potassium Area Under Curve (AUC), Cmin, Tmin | plasma potassium to evaluate drug systemic effect | predose, 15min, 30min, 1, 2, 4, 6, 8 hours postdose | 
| Heart Rate: Time averaged Heart Rate value: AUC0-t/t | Heart Rate to evaluate drug systemic effect | predose, 15min, 30min, 1, 2, 4, 6, 8 hours postdose | 
| Urinary Cortisol: Amount excreted in 0-8hours (Ae),8h cortisol urinary excretion normalized for 8h creatinine excretion (Ae/Aecreat). | Urinary cortisol to evaluate drug systemic effect | from predose up to 8 hours postdose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
asthma children NEXT DPI LABA ICS inhalation