Lung Bioavailability and Total Systemic Exposure to Beclomethasone17MonoPropionate and Formoterol Across Two Strengths of NEXThaler Inhalation Powder

Study Overview
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Brief Summary
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The study is aimed to assess the dose proportional total systemic exposure (when the administration is without the activated charcoal) to B17MP (active metabolite of BDP) and its lung bioavailability (when the administration is with the activated charcoal) after single inhalation of CHF 1535 NEXThaler DPI at two dose strengths. At the same time, the study will assess if the lung deposition and the total systemic exposure to Formoterol is affected by increasing doses of BDP.

Official Title
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A Phase II, Monocentric, Open, Randomized, 6-way Cross-over Clinical Pharmacology Study to Evaluate the Lung Bioavailability of BDP/B17MP and Formoterol and the Total Systemic Exposure Across Two Different Strengths of CHF 1535 NEXThaler Dry Powder Inhaler (Fixed Combination of Beclomethasone Dipropionate Plus Formoterol Fumarate 100/6 mcg and 200 mcg) Administered With and Without Activated Charcoal in Adult Asthmatic Patients.

Conditions
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Asthmatic

Intervention / Treatment
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* Drug: NEXThaler 100/6 mcg DPI
* Drug: Flixotide Accuhaler 500 mcg
* Drug: NEXThaler 200/6 mcg DPI
* Drug: NEXThaler placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of asthma as defined by Global Initiative for Asthma (GINA) 2011 Asthmatic patients already treated with low daily doses of Inhaled Corticosteroids (ICS) (eg budesonide or equivalent lower than 400 mcg/day) or low dose of ICS/Long Acting Beta2 Agonists (LABA) fixed combinations. Patients with Forced Expiratory Volume in 1 sec (FEV1) >= 70 % of predicted values Non or ex-smokers Body Mass Index (BMI) >= 18.5 and <= 32 kg/m2 Exclusion Criteria: Pregnant or lactating women unless using acceptable methods of contraception Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) History of near fatal asthma Patients with abnormal QTcF at screening Visit Hospitalization due to asthma exacerbation within 4 weeks prior to the screening visit or during the run-in period. Lower respiratory tract infection within 4 weeks prior to the screening visit or during the run-in period. History of drug addiction or excessive use of alcohol ; Diagnosis of restrictive lung disease. Patients treated with oral or parenteral corticosteroids in the previous 2 months before the screening visit (3 months for parenteral depot corticosteroids) Significant medical history or any laboratory abnormality indicative of a significant underlying condition

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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 100/6 mcg DPI<br>Single dose (4 inhalations)of NEXThaler 100/6 mcg DPI: total dose 400/24 mcg | Drug: NEXThaler 100/6 mcg DPI<br> <br> * Other names: Fixed combination of BDP plus formoterol fumarate;|
| Experimental: NEXThaler 200/6 mcg DPI<br>Single dose (4 inhalations)of NEXThaler 200/6 mcg DPI: total dose: 800/24 mcg | Drug: NEXThaler 200/6 mcg DPI<br> <br> * Other names: Fixed combination of BDP plus formoterol fumarate;|
| Placebo Comparator: NEXThaler placebo<br>Single dose (4 inhalations) | Drug: NEXThaler placebo<br>* Placebo comparator<br>|
| Experimental: NEXThaler 100/6 mcg plus CB<br>Single dose (4 inhalations) NEXThaler 100/6 mcg administered with activated charcoal (Charcoal Block): total dose 400/24 mcg | Drug: NEXThaler 100/6 mcg DPI<br> <br> * Other names: Fixed combination of BDP plus formoterol fumarate;|
| Experimental: NEXThaler 200/6 mcg plus CB<br>Single dose (4 inhalations) NEXThaler 200/6 mcg administered with activated charcoal (Charcoal Block): total dose 800/24 mcg | Drug: NEXThaler 200/6 mcg DPI<br> <br> * Other names: Fixed combination of BDP plus formoterol fumarate;|
| Active Comparator: Flixotide Accuhaler 500 mcg<br>Single dose (2 inhalations) of fluticasone propionate | Drug: Flixotide Accuhaler 500 mcg<br>* Active comparator<br>* Other names: Fluticasone Propionate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Formoterol AUC0-t and B17MP AUC0-t |  | from predose until 12 hr post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BDP pharmacokinetic (PK) parameters | The following parameters will be evaluated: AUC0-t, AUC0-12h, AUC0-inf, Cmax, tmax, t1/2 | from predose until 12 hr post dose | 
| Other PK parameter of B17MP and formoterol | the following pharmacokinetic parameters will be evaluated: AUC0-12, AUCinf, Cmax, tmax, t1/2 | from predose until 12 hours postdose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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patients, Adult