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

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

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.

Study Overview

• Status: Completed
• Conditions: Asthma, Exercise-Induced
• Intervention / Treatment: Drug: Comparator: Montelukast; Drug: Comparator: Salmeterol; Drug: Comparator: Placebo (montelukast); Drug: Comparator: Placebo (salmeterol)

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Organon and Co

Publications and helpful links

General Publications

• Philip G, Pearlman DS, Villaran C, Legrand C, Loeys T, Langdon RB, Reiss TF. Single-dose montelukast or salmeterol as protection against exercise-induced bronchoconstriction. Chest. 2007 Sep;132(3):875-83. doi: 10.1378/chest.07-0550. Epub 2007 Jun 15.

Study record dates

Study Major Dates

• Study Start: December 1, 2005
• Primary Completion (Actual): September 1, 2006
• Study Completion (Actual): September 1, 2006

Study Registration Dates

• First Submitted: October 26, 2005
• First Submitted That Met QC Criteria: October 27, 2005
• First Posted (Estimate): October 28, 2005

Study Record Updates

• Last Update Posted (Actual): February 2, 2022
• Last Update Submitted That Met QC Criteria: January 31, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Asthma, Exercise-Induced; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Leukotriene Antagonists; Hormone Antagonists; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Montelukast; Salmeterol Xinafoate
• Other Study ID Numbers: 0476-316; MK0476-316; 2005_043