Dose-response of Inhaled Formoterol Using Methacholine Challenge as a Bioassay

Study Overview
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Brief Summary
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The purpose of this study is to find out whether a difference between two doses of formoterol can be detected by methacholine challenge.

Detailed Description
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During the screening visit, subjects'vital signs (heart rate, blood pressure and temperature) will be measured and they will perform standard spirometry. If the results of this test are 70% of normal or greater, they will be examined by a physician, and blood (1 teaspoonful) and urine will be collected for routine laboratory tests (CBC and routine urinalysis). If they are a female, a pregnancy test will be performed. During the second visit, subjects will inhale 1 or 2 doses of formoterol, (Foradil Aerolizer 12 mcg/capsule) a long-acting bronchodilator and 1 hour later, perform a methacholine test. At the end of the methacholine test, they will be given albuterol to reverse the effects of methacholine. On the third study day, they will repeat the second visit but with the opposite dose of Foradil.

Official Title
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A Pilot Study to Evaluate the Dose-response of Inhaled Formoterol to Inhibit Airway Responsiveness to Methacholine in Patients With Mild Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: formoterol
* Drug: formoterol
* Device: Dry Powder Inhaler (Twisthaler)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-smoking male or female 18 60 years of age, with a previous diagnosis of asthma that has been stable for at least 4 weeks and which is unlikely to exacerbate during the study because of, for example, seasonal allergen exposure. Women of childbearing age must not be pregnant or nursing, and must be using an acceptable method of contraception. Ability to perform ATS/ERS-acceptable and reproducible spirometry7 Screening FEV1 ≥70% of predicted for height, age, sex, and race when short-acting inhaled bronchodilators are withheld for at least 6 hours At least a 20% decrease in FEV1 after inhaling ≤4 mg/mL of methacholine (i.e., a PC20 FEV1 ≤4 mg/mL) Can be taught to use the dry powder device in accordance with the product's medication guide. If using an oral inhaled or intranasal corticosteroid, dosage must be stable for at least 4 weeks. Exclusion Criteria: Allergy or sensitivity to inhaled methacholine, formoterol or to other β2 agonists Intolerance to other components of the inhaler or sensitivity to milk proteins Cigarette smoking in past year or >10 pack-year smoking history Respiratory tract infection within the last four weeks History of severe asthma attack requiring hospitalization in the previous 12 months Short course of oral and/or systemic corticosteroids in the past 4 weeks Inability to withhold caffeinated beverages for 12 hours or medications for appropriate intervals prior to each methacholine challenge Require treatment with beta-blockers (administered by any route), MAO inhibitors, tricyclic antidepressants, and/or maintenance therapy with systemic corticosteroids History and/or presence of pulmonary conditions (including but not limited to cystic fibrosis and bronchiectasis) other than asthma History of clinically-significant cardiovascular, renal, neurologic, liver or endocrine dysfunction. Patients with well-controlled hypertension, hypercholesterolemia or diabetes will not be excluded. If female, a positive urine β-HCG test Known or suspected substance abuse (e.g., alcohol, marijuana, etc.) and/or any other medical or psychological conditions that in the investigator's opinion should preclude study enrollment.

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

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 2<br>a single dose of 24 mcg of formoterol | Drug: formoterol<br>* a single dose of 24 mcg of formoterol delivered by dry powder inhaler (Twisthaler)<br>Device: Dry Powder Inhaler (Twisthaler)<br>* subjects inhaled deeply and forcefully and held their breath for 10 seconds for each dose<br>|
| Active Comparator: 1<br>a single dose of 12 mcg of formoterol | Drug: formoterol<br>* a single dose of 12 mcg of formoterol delivered by dry powder inhaler (Twisthaler)<br>Device: Dry Powder Inhaler (Twisthaler)<br>* subjects inhaled deeply and forcefully and held their breath for 10 seconds for each dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-dose PC20 | The PC20 is the provocational dose of methacholine causing a 20% drop in forced expiratory volume in the first second. | 3-7 days after visits 1 and 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FEV1 | The forced expiratory volume in the first second, expressed as a percent predicted. | 1 hour after dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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formoterol, methacholine challenge