Montelukast Compared With Placebo and Salmeterol in Exercise-Induced Bronchoconstriction (0476-316)

Study Overview
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Brief Summary
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To determine the effect of an approved medication being studied in support of a new approach in the prevention of exercise-induced asthma (a worsening of asthma caused by exercise, also known as exercise-induced bronchospasm), in patients who have a history of worsening asthma after exercise.

Official Title
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A Double-Blind, Randomized Multicenter, 3-Period, Crossover Study to Evaluate the Effects of a Single Dose of Montelukast Compared With Placebo and Salmeterol on Exercise-Induced Bronchoconstriction

Conditions
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Asthma, Exercise-Induced

Intervention / Treatment
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* Drug: Comparator: Montelukast
* Drug: Comparator: Salmeterol
* Drug: Comparator: Placebo (montelukast)
* Drug: Comparator: Placebo (salmeterol)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Physician-diagnosed exercise-induced bronchospasm Exclusion Criteria: Patient is, other than asthma, not in good, stable health. The Primary Investigator will evaluate whether there are other reasons why the patient may not participate.

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 45 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: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Montelukast - Salmeterol - Placebo | Drug: Comparator: Montelukast<br>* 1 dose montelukast 10 mg tablet given orally in one of three treatment periods<br>Drug: Comparator: Salmeterol<br>* 1 dose of 50 ug salmeterol given by inhalation in one of three treatment periods<br>Drug: Comparator: Placebo (montelukast)<br>* 1 dose matching-image placebo to montelukast tablet in two of three treatment periods<br>Drug: Comparator: Placebo (salmeterol)<br>* 1 dose matching-image placebo of salmeterol 50 ug inhalation in two of three treatment periods<br>|
| Experimental: 2<br>Montelukast - Placebo - Salmeterol | Drug: Comparator: Montelukast<br>* 1 dose montelukast 10 mg tablet given orally in one of three treatment periods<br>Drug: Comparator: Salmeterol<br>* 1 dose of 50 ug salmeterol given by inhalation in one of three treatment periods<br>Drug: Comparator: Placebo (montelukast)<br>* 1 dose matching-image placebo to montelukast tablet in two of three treatment periods<br>Drug: Comparator: Placebo (salmeterol)<br>* 1 dose matching-image placebo of salmeterol 50 ug inhalation in two of three treatment periods<br>|
| Experimental: 3<br>Salmeterol - Montelukast - Placebo | Drug: Comparator: Montelukast<br>* 1 dose montelukast 10 mg tablet given orally in one of three treatment periods<br>Drug: Comparator: Salmeterol<br>* 1 dose of 50 ug salmeterol given by inhalation in one of three treatment periods<br>Drug: Comparator: Placebo (montelukast)<br>* 1 dose matching-image placebo to montelukast tablet in two of three treatment periods<br>Drug: Comparator: Placebo (salmeterol)<br>* 1 dose matching-image placebo of salmeterol 50 ug inhalation in two of three treatment periods<br>|
| Experimental: 4<br>Salmeterol - Placebo - Montelukast | Drug: Comparator: Montelukast<br>* 1 dose montelukast 10 mg tablet given orally in one of three treatment periods<br>Drug: Comparator: Salmeterol<br>* 1 dose of 50 ug salmeterol given by inhalation in one of three treatment periods<br>Drug: Comparator: Placebo (montelukast)<br>* 1 dose matching-image placebo to montelukast tablet in two of three treatment periods<br>Drug: Comparator: Placebo (salmeterol)<br>* 1 dose matching-image placebo of salmeterol 50 ug inhalation in two of three treatment periods<br>|
| Experimental: 5<br>Placebo - Montelukast - Salmeterol | Drug: Comparator: Montelukast<br>* 1 dose montelukast 10 mg tablet given orally in one of three treatment periods<br>Drug: Comparator: Salmeterol<br>* 1 dose of 50 ug salmeterol given by inhalation in one of three treatment periods<br>Drug: Comparator: Placebo (montelukast)<br>* 1 dose matching-image placebo to montelukast tablet in two of three treatment periods<br>Drug: Comparator: Placebo (salmeterol)<br>* 1 dose matching-image placebo of salmeterol 50 ug inhalation in two of three treatment periods<br>|
| Experimental: 6<br>Placebo - Salmeterol - Montelukast | Drug: Comparator: Montelukast<br>* 1 dose montelukast 10 mg tablet given orally in one of three treatment periods<br>Drug: Comparator: Salmeterol<br>* 1 dose of 50 ug salmeterol given by inhalation in one of three treatment periods<br>Drug: Comparator: Placebo (montelukast)<br>* 1 dose matching-image placebo to montelukast tablet in two of three treatment periods<br>Drug: Comparator: Placebo (salmeterol)<br>* 1 dose matching-image placebo of salmeterol 50 ug inhalation in two of three treatment periods<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Percent Fall in Forced Expiratory Volume in 1 Second (FEV1) After Exercise Challenge at 2 Hours Post-dose in Patients With Exercise-Induced Bronchoconstriction (EIB) | In patients with EIB, the percent change from pre-exercise baseline FEV1 to the lowest FEV1 within 60 minutes after exercise challenge (2 hours post-dose). The FEV1 measurement obtained 5 minutes before the exercise challenge was the baseline, and was specific to each exercise challenge. | 0-60 minutes after the exercise challenge performed 2 hours after a single oral dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Requiring β-Agonist Rescue Medication After Exercise Challenge at 2 Hours Postdose |  | 0-90 minutes after the exercise challenge performed at 2 hours postdose | 
| Number of Patients Requiring β-Agonist Rescue Medication After Exercise Challenge at 8.5 Hours Postdose |  | 0-90 minutes after the exercise challenge performed at 8.5 hours postdose | 
| Number of Patients Requiring β-Agonist Rescue Medication After Exercise Challenge at 24 Hours Postdose |  | 0-90 minutes after the exercise challenge performed at 24 hours postdose | 
| Maximum Percent Fall in FEV1 After Exercise Challenge at 8.5 Hours Post-dose in Patients With EIB | In patients with EIB, the percent change from pre-exercise baseline FEV, to the lowest FEV1 within 60 minutes after exercise challenge (8.5 hours post-dose). The FEV1 measurement obtained 5 minutes before the exercise challenge was the baseline, and was specific to each exercise challenge. | 0-60 minutes after the exercise challenge performed 8.5 hours after a single oral dose | 
| Maximum Percent Fall in FEV1 After Exercise Challenge at 24 Hours Post-dose in Patients With EIB | In patients with EIB, the percent change from pre-exercise baseline FEV, to the lowest FEV1 within 60 minutes after exercise challenge (24 hours post-dose). The FEV1 measurement obtained 5 minutes before the exercise challenge was the baseline, and was specific to each exercise challenge. | 0-60 minutes after the exercise challenge performed 24 hours after a single oral dose | 
| Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60 Min) at 2 Hours Postdose | The measure included only the area below the pre-exercise baseline | 0-60 minutes after the exercise challenge at 2 hours postdose | 
| Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60 Min) at 8.5 Hours Postdose | The measure included only the area below the pre-exercise baseline | 0-60 minutes after the exercise challenge at 8.5 hours postdose | 
| Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60 Min) at 24 Hours Postdose | The measure included only the area below the pre-exercise baseline | 0-60 minutes after the exercise challenge at 24 hours postdose | 
| Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 2 Hours Postdose | The time to recovery from maximum percent fall is the duration between the time at which the maximum percent fall in FEV1 after exercise challenge occurs and the time when FEV1 returns to within 5% of the preexercise baseline for the first time. | Exercise challenge at 2 hours postdose | 
| Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 8.5 Hours Postdose | The time to recovery from maximum percent fall is the duration between the time at which the maximum percent fall in FEV1 after exercise challenge occurs and the time when FEV1 returns to within 5% of the preexercise baseline for the first time. | Exercise challenge at 8.5 hours postdose | 
| Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 24 Hours Postdose | The time to recovery from maximum percent fall is the duration between the time at which the maximum percent fall in FEV1 after exercise challenge occurs and the time when FEV1 returns to within 5% of the preexercise baseline for the first time. | Exercise challenge at 24 hours postdose |