Montelukast in Exercise-Induced Bronchospasm - 2004 (0476-275)

• Sponsor: Organon and Co (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00090142
• Collaborator: (none)
• Enrollment: 62
• Arms: 2
• Duration (Months): 5

Study Details

Study Description

Brief Summary

The purpose of this study is 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.

Condition or Disease	Intervention/Treatment	Phase
Asthma, Exercise-Induced	Drug: Comparator: Montelukast; Drug: Comparator: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 62 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: A Double-Blind, Randomized, Placebo-Controlled, Multicenter, 2-Period, Crossover Study to Evaluate the Effects of a Single Dose of Montelukast on Exercise-Induced Bronchospasm
• Study Start Date: May 1, 2004
• Actual Primary Completion Date: Oct 1, 2004
• Actual Study Completion Date: Oct 1, 2004

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Montelukast - Placebo	Drug: Comparator: Montelukast; Montelukast 10 mg tablet administered orally as a single witnessed dose before exercise challenge; Drug: Comparator: Placebo; Placebo tablet administered orally as a single witnessed dose before exercise challenge
Experimental: 2 Placebo - Montelukast	Drug: Comparator: Montelukast; Montelukast 10 mg tablet administered orally as a single witnessed dose before exercise challenge; Drug: Comparator: Placebo; Placebo tablet administered orally as a single witnessed dose before exercise challenge

Outcome Measures

Primary Outcome Measures

1. Maximum Percent Fall in FEV1 After Exercise Challenge at 2 Hours Post-dose Compared With Pre-exercise Baseline in Patients With Exercise-induced Bronchospasm (EIB) [Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed 2 hours after a single oral dose]

   In patients with EIB, the percent change from pre-exercise baseline FEV, 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.

Secondary Outcome Measures

1. Number of Patients Requiring ß-Agonist Rescue Medication After Exercise Challenge at 2 Hours Postdose [0-90 minutes after the exercise challenge performed at 2 hours postdose]

2. Number of Patients Requiring ß-Agonist Rescue Medication After Exercise Challenge at 12 Hours Postdose [0-90 minutes after the exercise challenge performed at 12 hours postdose]

3. Number of Patients Requiring ß-Agonist Rescue Medication After Exercise Challenge at 24 Hours Postdose [0-90 minutes after the exercise challenge performed at 24 hours postdose]

4. Maximum Percent Fall in FEV1 After Exercise Challenge at 12 Hours Postdose Compared With Pre-exercise Baseline in Patients With EIB [Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed 12 hours after a single oral dose]

   In patients with EIB, the percent change from pre-exercise baseline FEV, to the lowest FEV1 within 60 minutes after exercise challenge (12 hours post-dose). The FEV1 measurement obtained 5 minutes before the exercise challenge was the baseline, and was specific to each exercise challenge.

5. Maximum Percent Fall in FEV1 After Exercise Challenge at 24 Hours Postdose Compared With Pre-exercise Baseline in Patients With EIB [Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed 24 hours after a single oral dose]

   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.

6. 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 [Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed at 2 hours postdose]

   The measure included only the area below the pre-exercise baseline.

7. Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60 Min) at 12 Hours Postdose [Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed at 12 hours postdose]

   The measure included only the area below the pre-exercise baseline.

8. Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60min) at 24 Hours Postdose [Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed at 24 hours postdose]

   The measure included only the area below the pre-exercise baseline.

9. Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 2 Hours Postdose [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.

10. Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 12 Hours Postdose [Exercise challenge at 12 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.

11. Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 24 Hours Postdose [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 15 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with mild-to-moderate asthma

Exclusion Criteria:

• Medical history of a lung disorder (other than asthma) or a recent upper respiratory tract infection

• 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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Organon and Co

Investigators

• Study Director: Medical Monitor, Merck Sharp & Dohme Corp.

Study Documents (Full-Text)

None provided.

More Information

Publications

• Philip G, Villarán C, Pearlman DS, Loeys T, Dass SB, Reiss TF. Protection against exercise-induced bronchoconstriction two hours after a single oral dose of montelukast. J Asthma. 2007 Apr;44(3):213-7.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT00090142
• Other Study ID Numbers: 0476-275; 2004_009
• First Posted: Aug 26, 2004
• Last Update Posted: Feb 2, 2022
• Last Verified: Jan 1, 2022

• Additional relevant MeSH terms: Bronchial Spasm; Asthma, Exercise-Induced; Montelukast

Study Results

Participant Flow

Recruitment Details	Patients were randomized at 8 sites (7 in the US and 1 in Peru). Primary therapy period: May to October 2004.
Pre-assignment Detail	Patients who required excluded medications, or did not meet FEV1 criteria during the prestudy period were excluded from randomization. Patients who required a β-agonist after the exercise challenge and did not meet FEV1 criteria within 30 minutes of treatment were also excluded.

Arm/Group Title	Montelukast 10 mg in Period I Then Placebo in Period II	Placebo in Period I Then Montelukast 10 mg in Period II
Arm/Group Description	A montelukast 10-mg tablet (Treatment Period I) was taken orally in the morning as a single witnessed dose. This was followed by a 3-7 day washout period and then a montelukast matching-image placebo tablet (Treatment Period II) was taken orally in the morning as a single witnessed dose.	A montelukast matching-image placebo tablet (Treatment Period I) was taken orally in the morning as a single witnessed dose. This was followed by a 3-7 day washout and then a montelukast 10-mg tablet (Treatment Period II) was taken orally in the morning as a single witnessed dose.
Period Title: Treatment Period I
STARTED	31	31
COMPLETED	26	28
NOT COMPLETED	5	3
Period Title: Treatment Period I
STARTED	26	28
COMPLETED	25	28
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Overall Study Population
Arm/Group Description	All randomized patients
Overall Participants	62
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	24.4 (6.9)
Sex: Female, Male (Count of Participants)
Female	29 46.8%
Male	33 53.2%
Need for β-agonist rescue medication following exercise challenge (Number) [Number]
No	47 75.8%
Yes	15 24.2%
AUC for percent change from pre-exercise measurement FEV1 in L 0-60 mins after exercise challenge ((percent change) *minutes) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [(percent change) *minutes]	815.27 (516.83)
Maximum percent fall in Forced Expiratory Volume in 1 second (FEV1) post-exercise challenge (percent change from pre-exercise measure) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent change from pre-exercise measure]	26.86 (7.04)
Time to recovery from maximal percent fall (Minutes) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Minutes]	44.73 (32.23)

Outcome Measures

1. Primary Outcome

Title	Maximum Percent Fall in FEV1 After Exercise Challenge at 2 Hours Post-dose Compared With Pre-exercise Baseline in Patients With Exercise-induced Bronchospasm (EIB)
Description	In patients with EIB, the percent change from pre-exercise baseline FEV, 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.
Time Frame	Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed 2 hours after a single oral dose

Outcome Measure Data

Analysis Population Description

The primary efficacy analysis used the modified intention-to-treat (MITT) approach. Patients with data from only one period were not included in the analysis.

Arm/Group Title	Placebo	Montelukast 10 mg
Arm/Group Description	All Placebo patients from Treatment Periods I and II	All Montelukast 10 mg patients from Treatment Periods I and II
Measure Participants	54	54
Mean (Standard Deviation) [Percent Change]	17.50 (13.82)	11.70 (10.80)

2. Secondary Outcome

Title	Number of Patients Requiring ß-Agonist Rescue Medication After Exercise Challenge at 2 Hours Postdose
Time Frame	0-90 minutes after the exercise challenge performed at 2 hours postdose

Outcome Measure Data

Analysis Population Description

The secondary efficacy analysis used a modified intention-to-treat (MITT) approach. Patients with data from only one period were not included in the analysis.

Arm/Group Title	Placebo	Montelukast 10 mg
Arm/Group Description	All Placebo patients from Treatment Periods I and II	All Montelukast 10 mg patients from Treatment Periods I and II
Measure Participants	54	54
Patients requiring rescue medication	7 11.3%	2 NaN
Patients not requiring rescue medication	47 75.8%	52 NaN

3. Secondary Outcome

Title	Number of Patients Requiring ß-Agonist Rescue Medication After Exercise Challenge at 12 Hours Postdose
Time Frame	0-90 minutes after the exercise challenge performed at 12 hours postdose

Outcome Measure Data

Analysis Population Description

The secondary efficacy analysis used a modified intention-to-treat (MITT) approach. Patients with data from only one period were not included in the analysis.

Arm/Group Title	Placebo	Montelukast 10 mg
Arm/Group Description	All Placebo patients from Treatment Periods I and II	All Montelukast 10 mg patients from Treatment Periods I and II
Measure Participants	52	52
Patients requiring rescue medication	4 6.5%	2 NaN
Patients not requiring rescue medication	48 77.4%	50 NaN

4. Secondary Outcome

Title	Number of Patients Requiring ß-Agonist Rescue Medication After Exercise Challenge at 24 Hours Postdose
Time Frame	0-90 minutes after the exercise challenge performed at 24 hours postdose

Outcome Measure Data

Analysis Population Description

The secondary efficacy analysis used a modified intention-to-treat (MITT) approach. Patients with data from only one period were not included in the analysis.

Arm/Group Title	Placebo	Montelukast 10 mg
Arm/Group Description	All Placebo patients from Treatment Periods I and II	All Montelukast 10 mg patients from Treatment Periods I and II
Measure Participants	52	52
Patients requiring rescue medication	2 3.2%	2 NaN
Patients not requiring rescue medication	50 80.6%	50 NaN

5. Secondary Outcome

Title	Maximum Percent Fall in FEV1 After Exercise Challenge at 12 Hours Postdose Compared With Pre-exercise Baseline in Patients With EIB
Description	In patients with EIB, the percent change from pre-exercise baseline FEV, to the lowest FEV1 within 60 minutes after exercise challenge (12 hours post-dose). The FEV1 measurement obtained 5 minutes before the exercise challenge was the baseline, and was specific to each exercise challenge.
Time Frame	Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed 12 hours after a single oral dose

Outcome Measure Data

Analysis Population Description

The primary efficacy analysis used the modified intention-to-treat (MITT) approach. Patients with data from only one period were not included in the analysis.

Arm/Group Title	Placebo	Montelukast 10 mg
Arm/Group Description	All Placebo patients from Treatment Periods I and II	All Montelukast 10 mg patients from Treatment Periods I and II
Measure Participants	52	52
Mean (Standard Deviation) [Percent Change]	11.73 (11.64)	9.87 (11.43)

6. Secondary Outcome

Title	Maximum Percent Fall in FEV1 After Exercise Challenge at 24 Hours Postdose Compared With Pre-exercise Baseline in Patients With EIB
Description	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.
Time Frame	Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed 24 hours after a single oral dose

Outcome Measure Data

Analysis Population Description

The primary efficacy analysis used the modified intention-to-treat (MITT) approach. Patients with data from only one period were not included in the analysis.

Arm/Group Title	Placebo	Montelukast 10 mg
Arm/Group Description	All Placebo patients from Treatment Periods I and II	All Montelukast 10 mg patients from Treatment Periods I and II
Measure Participants	52	52
Mean (Standard Deviation) [Percent Change]	10.69 (12.31)	7.95 (10.80)

7. Secondary Outcome

Title	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
Description	The measure included only the area below the pre-exercise baseline.
Time Frame	Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed at 2 hours postdose

Outcome Measure Data

Analysis Population Description

The secondary efficacy analysis used a MITT approach. If a patient received β-agonist rescue medication during the 60 minutes following exercise challenge, then the last pre-rescue FEV1 measurement was carried forward to 60 minutes. Patients with data from only one period were not included in the analysis.

Arm/Group Title	Placebo	Montelukast 10 mg
Arm/Group Description	All Placebo patients from Treatment Periods I and II	All Montelukast 10 mg patients from Treatment Periods I and II
Measure Participants	54	54
Mean (Standard Deviation) [(percent change) *minutes]	582.6 (759.1)	284.7 (426.9)

8. Secondary Outcome

Title	Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60 Min) at 12 Hours Postdose
Description	The measure included only the area below the pre-exercise baseline.
Time Frame	Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed at 12 hours postdose

Outcome Measure Data

Analysis Population Description

The secondary efficacy analysis used a MITT approach. If a patient received β-agonist rescue medication during the 60 minutes following exercise challenge, then the last pre-rescue FEV1 measurement was carried forward to 60 minutes. Patients with data from only one period were not included in the analysis.

Arm/Group Title	Placebo	Montelukast 10 mg
Arm/Group Description	All Placebo patients from Treatment Periods I and II	All Montelukast 10 mg patients from Treatment Periods I and II
Measure Participants	52	52
Mean (Standard Deviation) [(percent change) *minutes]	314.0 (417.7)	241.7 (545.9)

9. Secondary Outcome

Title	Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60min) at 24 Hours Postdose
Description	The measure included only the area below the pre-exercise baseline.
Time Frame	Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed at 24 hours postdose

Outcome Measure Data

Analysis Population Description

The secondary efficacy analysis was an MITT approach. If a patient received β-agonist rescue medication during the 60 minutes following exercise challenge, then the last pre-rescue FEV1 measurement was carried forward to 60 minutes. Patients with data from only one period were not included in the analysis.

Arm/Group Title	Placebo	Montelukast 10 mg
Arm/Group Description	All Placebo patients from Treatment Periods I and II	All Montelukast 10 mg patients from Treatment Periods I and II
Measure Participants	52	52
Mean (Standard Deviation) [(percent change) *minutes]	269.6 (507.8)	223.1 (527.1)

10. Secondary Outcome

Title	Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 2 Hours Postdose
Description	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.
Time Frame	Exercise challenge at 2 hours postdose

Outcome Measure Data

Analysis Population Description

The secondary efficacy analysis used a modified intention-to-treat (MITT) approach. Patients with data from only one period were not included in the analysis.

Arm/Group Title	Placebo	Montelukast 10 mg
Arm/Group Description	All Placebo patients from Treatment Periods I and II	All Montelukast 10 mg patients from Treatment Periods I and II
Measure Participants	54	54
Mean (Standard Deviation) [Minutes]	34.23 (36.01)	15.87 (25.29)

11. Secondary Outcome

Title	Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 12 Hours Postdose
Description	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.
Time Frame	Exercise challenge at 12 hours postdose

Outcome Measure Data

Analysis Population Description

The secondary efficacy analysis used a modified intention-to-treat (MITT) approach. Patients with data from only one period were not included in the analysis.

Arm/Group Title	Placebo	Montelukast 10 mg
Arm/Group Description	All Placebo patients from Treatment Periods I and II	All Montelukast 10 mg patients from Treatment Periods I and II
Measure Participants	52	52
Mean (Standard Deviation) [Minutes]	23.40 (32.20)	9.42 (18.27)

12. Secondary Outcome

Title	Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 24 Hours Postdose
Description	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.
Time Frame	Exercise challenge at 24 hours postdose

Outcome Measure Data

Analysis Population Description

The secondary efficacy analysis used a modified intention-to-treat (MITT) approach. Patients with data from only one period were not included in the analysis.

Arm/Group Title	Placebo	Montelukast 10 mg
Arm/Group Description	All Placebo patients from Treatment Periods I and II	All Montelukast 10 mg patients from Treatment Periods I and II
Measure Participants	52	52
Mean (Standard Deviation) [Minutes]	13.81 (22.80)	9.47 (19.52)

Adverse Events

Time Frame	Adverse events (AEs) were collected during Period I and Period II, and up to and including 14 days after the last dose of study therapy
Adverse Event Reporting Description	The number of participants listed in the AE table (58 montelukast & 57 placebo) is the number that received treatment. Although a participant may have 2 or more AEs they are counted only once in a category. The same participant may appear in other categories.
Arm/Group Title	Montelukast 10 mg		Placebo
Arm/Group Description
All Cause Mortality
	Montelukast 10 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Montelukast 10 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/58 (0%)		0/57 (0%)
Other (Not Including Serious) Adverse Events
	Montelukast 10 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/58 (1.7%)		3/57 (5.3%)
Nervous system disorders
Headache	1/58 (1.7%)		3/57 (5.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.