Clinical Pharmacology of 35/4 NEXThaler® in Children 5-11 Years Old

Study Overview
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Brief Summary
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The study will be conducted in asthmatic children aged 5 to 11 years and is based on a single-dose, open-label, randomized, 2-way cross-over design where a Dry Powder Inhaler (DPI) fixed combination of beclometasone dipropionate (BDP) 35 μg plus formoterol fumarate (FF) 4 μg is compared with the free combination of licensed BDP DPI and FF DPI

Detailed Description
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This is a pharmacokinetic comparison of NEXThaler 35/4 μg versus the free combination of Beclomethasone DPI and Formoterol DPI in children (5 to 11 years old) of a formulation already approved in adults.

Official Title
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A Single-dose, Open-label, Randomized, 2-way Cross-over Study of CHF 1535 35/4 NEXThaler® (Fixed Combination of Beclometasone Dipropionate (BDP) 35 μg Plus Formoterol Fumarate (FF) 4 μg Versus the Free Combination of Licensed BDP DPI (Dry Powder Inhaler) and FF DPI in Asthmatic Children

Conditions
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Asthma

Intervention / Treatment
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* Drug: CHF 1535 35/4µg NEXThaler®
* Drug: free comb. beclomethasone DPI and formoterol DPI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male/female children with asthma stable enough, according to paediatrician opinion, to allow a wash out period from steroids of 3 days before study treatments. Male/female children with asthma on regular treatment with ICS or using short-acting inhaled 2-agonist as reliever to control asthma symptoms. Age ≥ 5 < 12 years (8 to 10 children in the age range 5-8 years old). Children with a forced expiratory volume in one second (FEV1)>70% of predicted values (% pred) after withholding 2-agonists treatment for a minimum of 4 h prior to screening and to each study treatment. A cooperative attitude and ability to be trained about the proper use of DPI, ability to use correctly the medical devices and compliant to study procedures Exclusion Criteria: Past or present diagnosis of cardiovascular, renal or liver disease. Known hypersensitivity to the active treatmen Exacerbation of asthma symptoms within 4 weeks prior to screening. 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
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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: NEXThaler® 35/4µg<br>CHF 1535 35/4µg NEXThaler® Dry Powder Inhaler, 4 inhalations. Total Dose: BDP 200µg FF 16µg | Drug: CHF 1535 35/4µg NEXThaler®<br>* 4 (four) inhalations (total dose: BDP/FF 140/16 µg)<br>|
| Active Comparator: Reference treatment<br>Drug: free comb. beclomethasone DPI and formoterol DPI 2 (two) inhalations BDP 100 µg DPI + 4 (four) inhalations FF 6 µg DPI (total dose: BDP 200 µg + FF 24 µg | Drug: free comb. beclomethasone DPI and formoterol DPI<br>* 2 (two) inhalations BDP 100 µg DPI + 4 (four) inhalations FF 6 µg DPI (total dose: BDP 200 µg + FF 24 µg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Area Under Curve (AUC0-t) for B17MP, active metabolite of BDP | 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 | 17MP: profile of pharmacokinetics | predose, 15min,30min,1,2,4,6,8 hours post dose | 
| BDP Area Under Curve (AUC) | BDP: profile of Pharmacokinetics | predose, 15min,30min,1,2,4,6,8 hours post dose | 
| Formoterol Area Under Curve (AUC), Cmax, Tmax, T1/2 [ | Formoterol: profile of pharmacokinetics | predose, 15min, 30 min, 1,2,4,6,8 hours postdose | 
| Formoterol Cmax | Formoterol: profile of pharmacokinetics | predose, 15min, 30 min, 1,2,4,6,8 hours postdose | 
| Formoterol Tmax | Formoterol: profile of pharmacokinetics | predose, 15min, 30 min, 1,2,4,6,8 hours postdose | 
| Formoterol T1/2 | Formoterol: profile of pharmacokinetics | predose, 15min, 30 min, 1,2,4,6,8 hours postdose | 
| plasma potassium Area Under Curve (AUC) | plasma potassium to evaluate drug systemic effect | predose, 15min, 30min, 1, 2, 4, 6, 8 hours postdose | 
| plasma potassium Cmin | plasma potassium to evaluate drug systemic effect | predose, 15min, 30min, 1, 2, 4, 6, 8 hours postdose | 
| plasma potassium Tmin | plasma potassium 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 | 
| B17MP Tmax | BDP: profile of pharmacokinetics | predose, 15min,30min,1,2,4,6,8 hours post dose | 
| B17MP T1/2 | BDP: profile of pharmacokinetics | predose, 15min,30min,1,2,4,6,8 hours post dose | 
| BDP Cmax | BDP: profile of pharmacokinetics | predose, 15min,30min,1,2,4,6,8 hours post dose | 
| BDP Tmax | BDP: profile of pharmacokinetics | predose, 15min,30min,1,2,4,6,8 hours post dose | 
| BDP T1/2 | BDP: profile of pharmacokinetics | predose, 15min,30min,1,2,4,6,8 hours post dose |