Duration of Long Acting Muscarinic Antagonist (LAMA) Bronchoprotection Against Methacholine Challenge

Study Overview
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Brief Summary
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The study will assess the duration of protection of single doses of 2 different long acting muscarinic antagonists against methacholine induced bronchoconstriction.

Official Title
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Duration of Bronchoprotection of the Long Acting Muscarinic Antagonists Tiotropium and Glycopyrronium Against Methacholine Induced Bronchoconstriction

Conditions
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Asthma

Intervention / Treatment
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* Drug: Tiotropium
* Drug: glycopyrronium
* Device: Respimat
* Device: Breezehaler


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male or female asthmatics > 19 years of age baseline methacholine PC20 less than or equal to 4mg/ml baseline lung function >65% predicted non-smoker and less than 10 pack year smoking history Exclusion Criteria: use of anticholinergic within 30 days of Visit 1 poorly controlled asthma pregnant or nursing respiratory illness within 4 weeks of Visit 1 exposure to an agent that triggered asthma worsening (e.g. allergen) within 4 weeks of Visit 1

Ages Eligible for Study
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Minimum Age: 19 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tiotropium<br>2 inhalations of 2.5mcg/inhalation tiotropium from Respimat inhaler and 1 inhalation of placebo from Breezehaler 1 hour prior to methacholine challenge | Drug: Tiotropium<br>* long acting muscarinic antagonist<br>* Other names: Spiriva;Device: Respimat<br>* inhaler device used to deliver active tiotropium or placebo<br>Device: Breezehaler<br>* inhaler device used to deliver active glycopyrronium or placebo<br>|
| Experimental: glycopyrronium<br>1 inhalation of 50mcg glycopyrronium from Breezehaler and 2 inhalations from placebo Respimat inhaler 1 hour prior to methacholine challenge | Drug: glycopyrronium<br>* long acting muscarinic antagonist<br>* Other names: Seebri;Device: Respimat<br>* inhaler device used to deliver active tiotropium or placebo<br>Device: Breezehaler<br>* inhaler device used to deliver active glycopyrronium or placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline methacholine bronchoprotection at 96 hours | assessed by dose shift of geometric mean methacholine PC20 data | pre treatment versus 96 hour post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline methacholine bronchoprotection at 1 hour | assessed by dose shift of geometric mean methacholine PC20 data | pre treatment versus 1 hour post treatment | 
| Change from baseline methacholine bronchoprotection at 24 hours | assessed by dose shift of geometric mean methacholine PC20 data | pre treatment versus 24 hours post treatment | 
| Change from baseline methacholine bronchoprotection at 48 hours | assessed by dose shift of geometric mean methacholine PC20 data | pre treatment versus 48 hours post treatment | 
| Change from baseline methacholine bronchoprotection at 72 hours | assessed by dose shift of geometric mean methacholine PC20 data | pre treatment versus 72 hours post treatment |