Exercise Induced Bronchoconstriction (0476-359)

A 3 Period, Double-Blind, Randomized Crossover Study to Evaluate the Effects of a Single Dose of Montelukast Compared With Placebo on Exercise-Induced Bronchoconstriction as Assessed by Hyperpolarized Gas Magnetic Resonance Imaging.

Exercise-induced bronchoconstriction (EIB) is a condition where airways tighten when you exercise and may cause coughing, wheezing, or shortness of breath. In many patients, this condition can cause lung function to drop making it harder to breath. An instrument called a spirometer is commonly used to measure lung function. This traditional means of assessing lung function in asthma is limited in its ability to provide information as to where in the lung the tightness is. Hyperpolarized helium magnetic resonance imaging (3He MRI) is a novel way to see the where air is going in the lungs using an MRI and special gas. The ability to see where the air can and cannot reach in the lungs may help show more accurately if a medication is working to make the asthma better. The purpose of this study is to examine patients with EIB in order to see if 3He MRI provides a better way to measure lung function. Patients will be given either montelukast sodium, a drug to improve the ability to breath with EIB, or placebo and then put on a treadmill to induce an occurrence of airway constriction. The patient's lung function will be measured more than once using both the spirometer and the 3He MRI.

Study Overview

• Status: Completed
• Conditions: Asthma, Exercise-induced
• Intervention / Treatment: Drug: montelukast sodium; Drug: Comparator: placebo (unspecified)

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient is a man or woman who is between the ages of 18 and 55 years of age at Visit 1
• Female patients of that are of childbearing potential must show they are not pregnant either by blood test Visit 1 and agree to use appropriate single barrier or hormonal contraception during the course of the study and continuing for at least 14 days following the patient's last study visit
• The patient has stable asthma without any worsening (e.g., requiring unscheduled visit to a physician, hospital or other healthcare resource, new medications or change in dose or frequency of current medications) within 4 weeks of Visit 1 and Visit 2
• Patient is a current non-smoker and if has a history of smoking, has not smoked for at least 6 months and has a smoking history of no more than 15 pack-years (i.e., 1 pack per day for 15 years)

Exclusion Criteria:

• Patient has donated a unit of blood within 4 weeks prior to Visit 1 or anticipates donating blood at any time during this study
• Patient has participated in a clinical trial involving an investigational or marketed medication within the 4 weeks prior to Visit 1 or anticipates participating in any other clinical trial during this study. Patient is currently a regular user, or a recent past abuser (within the past 5 years), of alcohol or illicit drugs
• Patient is a female who has given birth in the last 8 weeks of Visit 1 or breast feeding an infant
• Patient is pregnant, or intends to become pregnant during the time course of the study. Patient is hospitalized or has had a major surgical procedure, major trauma requiring medical attention, or significant illness requiring medical attention within 4 weeks of Visit 1
• Patient does not agree to limit caffeinated beverages and/or chocolate within 8 hours of study visits. Patient has had a worsening of their asthma within 4 weeks of Visit 1 or Visit 2 (i.e., requiring change in type, dose or frequency of medications and/or an unscheduled visit to a health care provider, including emergency room or hospital). Patient has unresolved signs and/or symptoms of an upper respiratory tract infection within 4 weeks of Visit 1 or Visit 2
• Patient is unwilling to restrict vigorous exercise (e.g., weight lifting or long distance running) or abstain from performing strenuous activity within 18 hours of any visit
• Patient has an implanted mechanically, electrically or magnetically activated device or any metal in their body which cannot be removed, including but not limited to: pacemakers, neurostimulators, biostimulators, implanted insulin pumps, aneurysm clips, bioprosthesis, artificial limb, metallic fragment or foreign body, shunt, surgical staples (including clips or metallic sutures) and/or ear implants

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: I; Three period crossover study, 7 week duration: During periods I-III patients will receive oral medication as a single dose before exercise challenge. For the three periods of this study patients will receive in a randomized sequence one dose of montelukast 10mg and a matching placebo during the other 2 periods.	Drug: montelukast sodium; single oral dose, before exercise challenge, of montelukast 10mg; 7 week duration.; Other Names: Singulair®; MK0476; Drug: Comparator: placebo (unspecified); single oral dose, before exercise challenge, of Pbo; 7 week duration.
Placebo Comparator: II; Three period crossover study, 7 week duration: During periods I-III patients will receive oral medication as a single dose before exercise challenge. For the three periods of this study patients will receive in a randomized sequence one dose of montelukast 10mg and a matching placebo during the other 2 periods.	Drug: montelukast sodium; single oral dose, before exercise challenge, of montelukast 10mg; 7 week duration.; Other Names: Singulair®; MK0476; Drug: Comparator: placebo (unspecified); single oral dose, before exercise challenge, of Pbo; 7 week duration.
Placebo Comparator: III; Three period crossover study, 7 week duration: During periods I-III patients will receive oral medication as a single dose before exercise challenge. For the three periods of this study patients will receive in a randomized sequence one dose of montelukast 10mg and a matching placebo during the other 2 periods.	Drug: montelukast sodium; single oral dose, before exercise challenge, of montelukast 10mg; 7 week duration.; Other Names: Singulair®; MK0476; Drug: Comparator: placebo (unspecified); single oral dose, before exercise challenge, of Pbo; 7 week duration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Ventilation volume by 3He MRI, ventilation volume defects by 3He MRI, pulmonary lung function by spirometer	5 minutes to 1 hour after exercise challenege

Secondary Outcome Measures

Outcome Measure	Time Frame
Reproducability of ventilation volume and ventilation volume defects as measured by 3He MRI	3-7 days apart.

Collaborators and Investigators

• Sponsor: Organon and Co

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: April 22, 2008
• First Submitted That Met QC Criteria: April 22, 2008
• First Posted (Estimate): April 23, 2008

Study Record Updates

• Last Update Posted (Actual): February 14, 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; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Asthmatic Agents; Respiratory System Agents; Leukotriene Antagonists; Hormone Antagonists; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers; Montelukast
• Other Study ID Numbers: 0476-359; MK0476-359; 2008_502

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

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