Comparing the Efficacy of Bricanyl M2 and Bricanyl M3 at 0.5 and 1.5 mg Dose Levels, to Allow for a Switch From Bricanyl Turbuhaler M2 to Bricanyl Turbuhaler M3

Study Overview
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Brief Summary
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A randomised, double-blind, double-dummy, multi-site, phase III, single dose, 4-way cross-over pharmacodynamic study evaluating the efficacy of Bricanyl Turbuhaler M3 compared to Bricanyl Turbuhaler M2 by studying the protective effect on methacholine induced bronchoconstriction in patients with stable, mild to moderate asthma

Detailed Description
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The study will include female and male patients, between 18 and 65 years old, with stable, mild to moderate asthma who are on short acting β2-agonist (SABA) alone, on low dose inhaled corticosteroid (ICS) (200-400 µg budesonide or corresponding) or on a combination of low dose ICS and long acting β2-agonists (LABA). Approximately 60 patients will be randomised in order to have 49 completed. The primary objective is to demonstrate therapeutic equivalence between Bricanyl Turbuhaler M3 and Bricanyl Turbuhaler M2 using bronchoprotective effect. Outcome measure: PC20 (Methacholine provocative concentration causing a 20% drop in FEV1). The safety objective is to compare safety of Bricanyl Turbuhaler M2 and Bricanyl Turbuhaler M3. Outcome measure Adverse Events/Serious. Study period Q1 2015 - Q1 2016.

Official Title
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A Randomised, Double-blind, Double-dummy, Multi-site, Phase III, Single Dose, 4-way Cross-over Pharmacodynamic Study Evaluating the Efficacy of Bricanyl Turbuhaler M3 Compared to Bricanyl Turbuhaler M2 by Studying the Protective Effect on Methacholine Induced Bronchoconstriction in Patients With Stable, Mild to Moderate Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: Terbutaline sulphate
* Drug: Terbutaline sulphate
* Drug: Placebo for terbutaline sulphate
* Drug: Placebo for terbutaline sulphate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Female and male aged 18 and 65 years. At least 6 months of documented clinical diagnosis of asthma as defined by GINA 2012 or American Thoracic Society (Expert Panel Report 3 2007) prior to visit 1 Stable asthmatics on SABA alone, on low dose ICS (200-400 µg budesonide corresponding) or on fixed combination of low ICS/LABA At the enrolment visit 1a, the visit baseline FEV1 must be ≥80 % of that predicted normal (NHANES III). For LABA patients the visit baseline FEV1 must be ≥80 % of that predicted normal (NHANES III) at both visit 1a and visit 1b. If not, the patient will be withdrawn from the study At the enrolment visits 1a or 1b (LABA patients only) and at the end of run-in period, visit 2, eligible patients should demonstrate an airway responsiveness to methacholine PC20 <8 mg/mL. If not, the patient will be withdrawn from the study Capable of using Turbuhaler inhalation device as judged by investigator. Exclusion Criteria: Diagnosed with COPD or history of cystic fibrosis, bronchiectasis or other respiratory diseases Pregnancy, breast-feeding, lactation, or planned pregnancy during the study. Fertile women not using acceptable contraceptive measures Conditions which could alter airway reactivity to methacholine (e.g. pneumonia, upper respiratory tract infection, viral bronchitis and/or sinobronchitis) within past six weeks Exacerbation due to asthma or change in asthma medication during the last 3 months prior to enrolment Night time awakenings due to asthma symptoms on 2 consecutive nights during the last 4 weeks prior to enrolment Smokers 6 months prior to the study start or with a history of smoking of more than 10 pack years (e.g. 20 cigarettes/day for at least 10 years, or 10 cigarettes/day for at least 20 years, or equal).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Bricanyl Turbuhaler M2, Active<br>Terbutaline sulphate powder for inhalation, 0.5 mg terbutaline per inhalation | Drug: Terbutaline sulphate<br>* Bricanyl Turbuhaler M2<br>* Other names: Terbutaline sulphate powder for inhalation, 0.5 mg (metered dose) terbutaline per inhalation;|
| Active Comparator: Bricanyl Turbuhaler M3, Active<br>Terbutaline sulphate powder for inhalation, 0.4 mg terbutaline per inhalation | Drug: Terbutaline sulphate<br>* Bricanyl Turbuhaler M3<br>* Other names: Terbutaline sulphate powder for inhalation, 0.4 mg (delivered dose) terbutaline per inhalation;|
| Placebo Comparator: Turbuhaler M2, Placebo<br>Placebo powder for inhalation | Drug: Placebo for terbutaline sulphate<br>* Placebo Turbuhaler M2<br>* Other names: Placebo powder for inhalation;|
| Placebo Comparator: Turbuhaler M3, Placebo<br>Placebo powder for inhalation | Drug: Placebo for terbutaline sulphate<br>* Placebo Turbuhaler M3<br>* Other names: Placebo powder for inhalation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Provocative Concentration of Methacholine Which Produces a 20% Fall in FEV1 (PC20) |  | 4 cross-over treatments (<1 day each) with 2-10 days between treatment washout periods | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Inhalation, Pharmacodynamic, Patients,