The Effect of Montelukast on Difficulty in Breathing After Exercise in Pediatric Patients (MK0476-377)(COMPLETED)

A Double-Blind, Placebo-Controlled, Multicenter, Crossover Study to Evaluate the Effects of a Single Oral Dose of Montelukast, Compared With Placebo, on Exercise-Induced Bronchoconstriction (EIB) in Pediatric Patients Aged 4 to 14 Years

This study will see if there is a change in breathing after exercising when the child receives study drug ( montelukast or placebo). Breathing will be measured by a spirometer before exercising and measured again several times after exercising.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 364
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The child is 4 years to 14 years of age
• The child is a non smoker
• The child has exercise-induced bronchoconstriction (EIB)

Exclusion Criteria:

• The child has active or chronic breathing disease, other than asthma
• The child has required insertion of a breathing tube for asthma
• The child had major surgery within the last 4 weeks
• The child is currently in the hospital
• The child has or had an upper respiratory tract infection within the last 2 weeks
• The child has been hospitalized or visited the emergency room or had a change in their medication for asthma within the last 4 weeks
• The child has been in a research study in the last 4 weeks
• The child has stomach, brain, heart, kidney or liver disease
• The child drinks more that 4 caffeinated drinks a day

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Montelukast Sodium; Participants 4-5 years: A single dose of 4 mg Montelukast chewable tablet daily, crossing over to matching placebo (Pbo) after a 3- to 7-day washout period (no participants 4-5 years were enrolled) Participants 6-14 years: A single dose of 5 mg Montelukast chewable tablet daily, crossing over to matching Pbo after a 3- to 7-day washout period	Drug: Comparator: montelukast sodium; Patients 4-5 years: 4 mg Montelukast chewable tablet daily Patients 6-14 years: 5 mg chewable tablet daily
Experimental: Placebo; Participants 4-5 years: A single dose of 4 mg Pbo chewable tablet daily, crossing over to Montelukast 4 mg chewable tablet after a 3- to 7-day washout period (no participants 4-5 years of age were enrolled) Participants 6-14 years: A single dose of 5 mg Pbo chewable tablet daily, crossing over to Montelukast 5 mg chewable tablet after a 3- to 7-day washout period	Drug: Comparator: Comparator: placebo (unspecified); Patients 4-5 years: 4 mg Pbo chewable tablet daily Patients 6-14 years: 5 mg Pbo chewable tablet daily

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 Postdose	Maximum Percent Fall in FEV1 was defined as the % change from pre-exercise baseline FEV1 to the lowest FEV1 within 60 mins (minutes) after exercise. Spirometry measurements were taken 5 mins prior to each exercise challenge and immediately, 5, 10, 15, 30, 45, & 60 mins after each exercise challenge. The 2-hour exercise challenges occurred 2 hours after the witnessed dose of study medication. The calculation used to produce the results was [100*(1-(X/Y))] where X= the lowest FEV1 within 60 mins after exercise & Y= pre-exercise baseline FEV1. Smaller values mean greater response to therapy.	Pre-exercise baseline and 0-60 minutes after the exercise challenge performed 2 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Percent Fall in FEV1 After Exercise Challenge at 24 Hours Post-dose	Maximum Percent Fall in FEV1 was defined as the % change from pre-exercise baseline FEV1 to the lowest FEV1 within 60 mins after exercise. Spirometry measurements were taken 5 mins prior to each exercise challenge and immediately, 5, 10, 15, 30, 45, & 60 mins after each exercise challenge. The 24-hour exercise challenges occurred 20-24 hours after the witnessed dose of study medication. The calculation used to produce the resulted results was [100*(1-(X/Y))] where X= the lowest FEV1 within 60 mins after exercise & Y= pre-exercise baseline FEV1. Smaller values mean greater response to therapy.	Pre-exercise baseline and 0-60 minutes after the exercise challenge performed 24 hours post-dose
Area Under the Curve for FEV1 Percent Fall From Pre-exercise Baseline to 60 Minutes Following Exercise Challenge (AUC0-60 Min) at 2 Hours Post-dose	AUC0-60min was defined as the Area Under the Curve for FEV1 percent change from pre-exercise baseline to the 60 mins following exercise challenge. The area was computed by applying the trapezoidal rule, and including only the area below the pre-exercise baseline. If a participant received β-agonist during the 60 mins after the exercise challenge, the FEV1 measurements obtained after β-agonist administration were excluded and the last pre-rescue FEV1 measurement was carried forward to the 60 mins time point in the calculation of the AUC0-60 min. Smaller values mean greater response to therapy.	Pre-exercise baseline to 60 minutes after the exercise challenge performed 2 hours post-dose
Area Under the Curve for FEV1 Percent Fall From Pre-exercise Baseline to 60 Minutes Following Exercise Challenge (AUC0-60 Min) at 24 Hours Post-dose	AUC0-60min was defined as the Area Under the Curve for FEV1 percent change from pre-exercise baseline to the 60 mins following exercise challenge. The area was computed by applying the trapezoidal rule, and including only the area below the pre-exercise baseline. If a participant received β-agonist during the 60 mins after the exercise challenge, the FEV1 measurements obtained after β-agonist administration were excluded and the last pre-rescue FEV1 measurement was carried forward to the 60 mins time point in the calculation of the AUC0-60 min. Smaller values mean greater response to therapy.	Pre-exercise baseline to 60 minutes after the exercise challenge performed 24 hours post-dose
Time to Recovery From Maximum Percent Fall in FEV1 at 2 Hours Post-dose	This endpoint was defined as the duration between the time at which the maximum percent fall in FEV1 occurred & the time when the percent fall in FEV1 returned to within 5% of the pre-exercise baseline for the first time. Spirometry measurements were taken 5 mins prior to each exercise challenge & immediately, 5, 10, 15, 30, 45, & 60 mins after each exercise challenge. If participant had not returned to within 5% of the pre-exercise FEV1 value by 60 mins, then measurements were obtained at 75 & 90 mins. The 2-hour exercise challenges occurred 2 hours after the witnessed dose of medication.	0-60 minutes and 0-90 minutes after the exercise challenge at 2 hours postdose
Time to Recovery From Maximum Percent Fall in FEV1 at 24 Hours Post-dose	This endpoint was defined as the duration between the time at which the maximum percent fall in FEV1 occurred & the time when the percent fall in FEV1 returned to within 5% of the pre-exercise baseline for the first time. Spirometry measurements were taken 5 mins prior to each exercise challenge & immediately, 5, 10, 15, 30, 45 & 60 mins after each exercise challenge. If participant had not returned to within 5% of the pre-exercise FEV1 value by 60 mins, then measurements were obtained at 75 & 90 mins. The 24-hour exercise challenges occurred 20-24 hours after the witnessed dose of medication.	0-60 minutes and 0-90 minutes after the exercise challenge at 24 hours postdose
Number of Participants Requiring Rescue Medication at 2 Hours Postdose	This endpoint was defined as the number of participants requiring rescue medication with β-agonist within the 90 mins following exercise challenge. The 2-hour exercise challenges occurred 2 hours after the witnessed dose of study medication.	0-90 minutes after the exercise challenge at 2 hours postdose
Number of Participants Requiring Rescue Medication at 24 Hours Postdose	This endpoint was defined as the number of participants requiring rescue medication with β-agonist within the 90 mins following exercise challenge. The 24-hour exercise challenges occurred 20-24 hours after the witnessed dose of study medication.	0-90 minutes after the exercise challenge at 24 hours postdose

Collaborators and Investigators

• Sponsor: Organon and Co

Publications and helpful links

General Publications

• Wasfi YS, Kemp JP, Villaran C, Massaad R, Xin W, Smugar SS, Knorr BA, Philip G. Onset and duration of attenuation of exercise-induced bronchoconstriction in children by single-dose of montelukast. Allergy Asthma Proc. 2011 Nov-Dec;32(6):453-9. doi: 10.2500/aap.2011.32.3482.

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: September 21, 2007
• First Submitted That Met QC Criteria: September 25, 2007
• First Posted (Estimate): September 26, 2007

Study Record Updates

• Last Update Posted (Actual): February 7, 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: 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: 0476-377; 2007_586

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

http://engagezone.msd.com/ds_documentation.php