Montelukast in Exercise-Induced Bronchospasm - 2003 (0476-270)

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00092131

Enrollment

Registered

2004-09-24

Start date

2003-06-30

Completion date

2003-11-30

Last updated

2022-02-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Asthma, Exercise-Induced

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 participants who have a history of worsening asthma after exercise.

Interventions

DRUGComparator: Montelukast

Montelukast 10 mg tablet administered orally as a single witnessed dose before exercise challenge

DRUGComparator: Placebo

Placebo tablet administered orally as a single witnessed dose before exercise challenge

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

PREVENTION

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

15 Years to 45 Years

Healthy volunteers

Inclusion criteria

* Participants with mild-to-moderate asthma

Exclusion criteria

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

Design outcomes

Primary

Measure	Time frame	Description
Maximum Percent Fall in FEV1 After Exercise Challenge at 2 Hours Postdose 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 Participants 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.

Secondary

Measure	Time frame	Description
Number of Participants Requiring ß-Agonist Rescue Medication After Exercise Challenge at 12 Hours Postdose	0-90 minutes after the exercise challenge performed at 12 hours postdose	—
Number of Participants Requiring ß-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 12 Hours Postdose 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 12 hours after a single oral dose	In patients with EIB, the percent change from pre-exercise baseline FEV1 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.
Maximum Percent Fall in FEV1 After Exercise Challenge at 24 Hours Postdose 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 24 hours after a single oral dose	In patients with EIB, the percent change from pre-exercise baseline FEV1 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.
Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60min) 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.
Number of Participants Requiring ß-Agonist Rescue Medication After Exercise Challenge at 2 Hours Postdose	0-90 minutes after the exercise challenge performed at 2 hours postdose	—
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.
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 occurs and the time when FEV1 returns to within 5% of the preexercise baseline for the first time.
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 occurs and the time when FEV1 returns to within 5% of the preexercise baseline for the first time.
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 occurs and the time when FEV1 returns to within 5% of the preexercise baseline for the first time.
Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60min) 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.

Participant flow

Recruitment details

Patients were randomized at 9 sites. Primary therapy period: July to November 2003

Pre-assignment details

Patients who required excluded medications, or did not meet forced expiratory volume in 1 second (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.

Participants by arm

Arm	Count
Overall Study Population All randomized patients	51
Total	51

Withdrawals & dropouts

Period	Reason	FG000	FG001
Treatment Period I	Adverse Event	1	0
Treatment Period II	Adverse Event	0	1

Baseline characteristics

Characteristic	Overall Study Population
Age, Continuous	24.5 years STANDARD_DEVIATION 5.9
AUC for percent change from pre-exercise measurement FEV1 in L 0-60 mins after exercise challenge	762.59 (percent change) *minutes STANDARD_DEVIATION 380.34
Maximum Percent Fall in forced expiratory volume in 1 second (FEV1) post-exercise challenge	27.63 Percent change from pre-exercise measure STANDARD_DEVIATION 5.6
Need for β-agonist rescue medication following exercise challenge No	47 Participants
Need for β-agonist rescue medication following exercise challenge Yes	4 Participants
Sex: Female, Male Female	27 Participants
Sex: Female, Male Male	24 Participants
Time to recovery from maximal percent fall in FEV1 after exercise challenge	45.15 Minutes STANDARD_DEVIATION 29.7

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	0 / 25	0 / 26
serious Total, serious adverse events	0 / 25	0 / 26

Outcome results

Primary

Maximum Percent Fall in FEV1 After Exercise Challenge at 2 Hours Postdose Compared With Pre-exercise Baseline in Patients With Exercise-induced Bronchospasm (EIB)

In Participants 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.

Time frame: Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed 2 hours after a single oral dose

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

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Maximum Percent Fall in FEV1 After Exercise Challenge at 2 Hours Postdose Compared With Pre-exercise Baseline in Patients With Exercise-induced Bronchospasm (EIB)	22.33 Percent Change	Standard Deviation 13.1
Montelukast 10 mg	Maximum Percent Fall in FEV1 After Exercise Challenge at 2 Hours Postdose Compared With Pre-exercise Baseline in Patients With Exercise-induced Bronchospasm (EIB)	10.80 Percent Change	Standard Deviation 7.88

Secondary

Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60min) at 12 Hours Postdose

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

Population: 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	Measure	Value (MEAN)	Dispersion
Placebo	Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60min) at 12 Hours Postdose	389.55 (percent change) *minutes	Standard Deviation 317.09
Montelukast 10 mg	Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60min) at 12 Hours Postdose	152.27 (percent change) *minutes	Standard Deviation 179.49

Secondary

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

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

Arm	Measure	Value (MEAN)	Dispersion
Placebo	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	409.50 (percent change) *minutes	Standard Deviation 426.55
Montelukast 10 mg	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	120.06 (percent change) *minutes	Standard Deviation 119.77

Secondary

Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60min) at 2 Hours Postdose

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

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60min) at 2 Hours Postdose	702.13 (percent change) *minutes	Standard Deviation 674.98
Montelukast 10 mg	Area Under the Curve for FEV1 Percent Change From Preexercise Baseline During the 60 Minutes Following Exercise Challenge (AUC 0-60min) at 2 Hours Postdose	182.46 (percent change) *minutes	Standard Deviation 235.94

Secondary

Maximum Percent Fall in FEV1 After Exercise Challenge at 12 Hours Postdose Compared With Pre-exercise Baseline in Patients With Exercise-induced Bronchospasm (EIB)

In patients with EIB, the percent change from pre-exercise baseline FEV1 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

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

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Maximum Percent Fall in FEV1 After Exercise Challenge at 12 Hours Postdose Compared With Pre-exercise Baseline in Patients With Exercise-induced Bronchospasm (EIB)	16.12 Percent Change	Standard Deviation 10.23
Montelukast 10 mg	Maximum Percent Fall in FEV1 After Exercise Challenge at 12 Hours Postdose Compared With Pre-exercise Baseline in Patients With Exercise-induced Bronchospasm (EIB)	8.35 Percent Change	Standard Deviation 7.5

Secondary

Maximum Percent Fall in FEV1 After Exercise Challenge at 24 Hours Postdose Compared With Pre-exercise Baseline in Patients With Exercise-induced Bronchospasm (EIB)

In patients with EIB, the percent change from pre-exercise baseline FEV1 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

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

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Maximum Percent Fall in FEV1 After Exercise Challenge at 24 Hours Postdose Compared With Pre-exercise Baseline in Patients With Exercise-induced Bronchospasm (EIB)	16.86 Percent Change	Standard Deviation 11.69
Montelukast 10 mg	Maximum Percent Fall in FEV1 After Exercise Challenge at 24 Hours Postdose Compared With Pre-exercise Baseline in Patients With Exercise-induced Bronchospasm (EIB)	8.33 Percent Change	Standard Deviation 7.34

Secondary