A Study to Evaluate the Onset of Relief From Methacholine-induced Bronchoconstriction With CHF1535 NEXThaler in Asthmatic Patients.

Study Overview
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Brief Summary
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The clinical trial is designed to evaluate the non-inferiority of CHF1535 100/6 µg NEXThaler versus CHF1535 100/6 µg pMDI on the onset of relief from methacholine-induced bronchospasm, in terms of pulmonary function (i.e. change in Forced Expiratory Volume in the 1st second, FEV1, from baseline to 5 min after study drug intake) in asthmatic patients.

Official Title
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A Single Dose, Randomised, Double Blind, Double Dummy, Placebo Controlled, 3-way Crossover Clinical Study, Comparing the Onset of Relief From Methacholine-induced Bronchoconstriction With CHF1535 100/6 µg NEXThaler® Versus CHF1535 100/6 µg pMDI in Asthmatic Patients.

Conditions
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Asthma

Intervention / Treatment
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* Drug: CHF1535 NEXThaler
* Drug: CHF1535 pMDI
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent form obtained Minimum required Peak Inspiratory Flow (PIF) to activate NEXThaler Pre-bronchodilator FEV1 of at least 65% Positive response to methacholine challenge test Previous treatment with low-medium doses of Inhaled Corticosteroids (ICS) or ICS/Long-acting beta2-agonist (LABA) as per Global Initiative for Asthma (GINA) 2016 guidelines For females: non-pregnant, non-lactacting and using highly effective contraceptive methods. Exclusion Criteria: Clinically relevant and uncontrolled concomitant diseases Abnormal clinically relevant ECG Presence of aortic aneurism Uncontrolled hypertension Intake of non-permitted concomitant medications Participation in another clinical trials in the previous 8 weeks Seasonal variation in asthma Recent occurrence of asthma exacerbations Hypersensitivity to any product used in the trial, including excipients Heavy caffeine drinkers History of alcohol/drug abuse Smokers

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CHF1535 NEXThaler<br>CHF1535 100/6 NEXThaler (Beclometasone dipropionate 100 µg + formoterol fumarate 6 µg) | Drug: CHF1535 NEXThaler<br>* Rescue treatment<br>* Other names: Foster NEXThaler;|
| Active Comparator: CHF1535 pMDI<br>CHF1535 100/6 pMDI (Beclometasone dipropionate 100 µg + formoterol fumarate 6 µg) | Drug: CHF1535 pMDI<br>* Rescue treatment<br>* Other names: Foster;|
| Placebo Comparator: Placebo<br>Double dummy study: placebo is for both CHF1535 pMDI and CHF1535 NEXThaler | Drug: Placebo<br>* Rescue treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in FEV1 5-min post-dose | Change in FEV1 from baseline (baseline is the post-diluent value, before methacholine challenge test) | 5 min post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in FEV1 other time points | Change in FEV1 from baseline (baseline is the post-diluent value, before methacholine challenge test) | Up to 30 min post-dose | 
| FEV1 AUC0-10min | FEV1 area under the curve from dosing to 10 min post-dose | From dosing to 10 min post-dose | 
| Time to recovery in FEV1 | Time to return to 85% of baseline value | From dosing to 30 min post-dose | 
| Change in Borg scale | Change in Borg scale from the end of the methacholine challenge test | Up to 30 min post-dose | 
| Time to recovery in Borg scale | 50% decrease from the post-methacholine challenge value | Up to 30 min post-dose |