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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00245570

Enrollment

Registered

2005-10-28

Start date

2005-12-31

Completion date

2006-09-30

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

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.

Interventions

DRUGComparator: Montelukast

1 dose montelukast 10 mg tablet given orally in one of three treatment periods

DRUGComparator: Salmeterol

1 dose of 50 ug salmeterol given by inhalation in one of three treatment periods

DRUGComparator: Placebo (montelukast)

1 dose matching-image placebo to montelukast tablet in two of three treatment periods

DRUGComparator: Placebo (salmeterol)

1 dose matching-image placebo of salmeterol 50 ug inhalation in two of three treatment periods

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

* 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.

Design outcomes

Primary

Measure	Time frame	Description
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)	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 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 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	0-60 minutes after the exercise challenge performed 8.5 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 (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.
Maximum Percent Fall in FEV1 After Exercise Challenge at 24 Hours Post-dose in Patients With EIB	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.
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	0-60 minutes after the exercise challenge at 2 hours postdose	The measure included only the area below the pre-exercise baseline
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	—
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	0-60 minutes after the exercise challenge 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 after exercise challenge 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 8.5 Hours Postdose	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.
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.
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	0-60 minutes after the exercise challenge at 8.5 hours postdose	The measure included only the area below the pre-exercise baseline

Participant flow

Recruitment details

Patients were randomized at 5 sites (4 in the US and 1 in Peru). Primary therapy period: December 2005 to August 2006

Pre-assignment details

Patients who required excluded medications, or did not meet FEV1 criteria during the prestudy period were excluded from randomization.

Participants by arm

Arm	Count
Overall Study Population All randomized patients	47
Total	47

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005
Washout Between Periods III and IV	Adverse Event	0	1	0	0	0	0

Baseline characteristics

Characteristic	Overall Study Population
Age, Continuous	26.0 years STANDARD_DEVIATION 7.92
Area under the FEV1 percent change from baseline time curve for 0-60 mins after exercise challenge	957.46 % * minutes STANDARD_DEVIATION 518.69
Maximum percent fall in forced expiratory volume in 1 second (FEV1) post-exercise challenge	27.75 Percent Change from Baseline STANDARD_DEVIATION 6.26
Need for β-agonist rescue medication following exercise challenge No	31 participants
Need for β-agonist rescue medication following exercise challenge Yes	16 participants
Sex: Female, Male Female	24 Participants
Sex: Female, Male Male	23 Participants
Time to recovery from maximal percent fall	55.03 Minutes STANDARD_DEVIATION 32.62

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	0 / 7	0 / 8	0 / 8	0 / 8	0 / 8	0 / 8
serious Total, serious adverse events	0 / 7	0 / 8	0 / 8	0 / 8	0 / 8	0 / 8

Outcome results

Primary

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.

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

Population: 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	Measure	Value (MEAN)	Dispersion
Montelukast 10 mg	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)	13.15 Percent Change from Baseline	Standard Deviation 10.28
Salmeterol 50-μg	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)	10.46 Percent Change from Baseline	Standard Deviation 9.95
Placebo	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)	21.86 Percent Change from Baseline	Standard Deviation 13.44

Secondary

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

Time frame: 0-60 minutes after the exercise challenge at 24 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
Montelukast 10 mg	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	231.09 Percent * minutes	Standard Deviation 413.73
Salmeterol 50-μg	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	554.93 Percent * minutes	Standard Deviation 649.52
Placebo	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	395.96 Percent * minutes	Standard Deviation 464.92

Secondary

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

Time frame: 0-60 minutes after the exercise challenge at 2 hours postdose

Arm	Measure	Value (MEAN)	Dispersion
Montelukast 10 mg	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	254.60 Percent * minutes	Standard Deviation 241.17
Salmeterol 50-μg	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	293.05 Percent * minutes	Standard Deviation 362.33
Placebo	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	710.43 Percent * minutes	Standard Deviation 529.91

Secondary

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

Time frame: 0-60 minutes after the exercise challenge at 8.5 hours postdose

Arm	Measure	Value (MEAN)	Dispersion
Montelukast 10 mg	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	191.01 Percent * minutes	Standard Deviation 166.24
Salmeterol 50-μg	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	276.26 Percent * minutes	Standard Deviation 226.37
Placebo	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	511.28 Percent * minutes	Standard Deviation 566.3

Secondary

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.

Time frame: 0-60 minutes after the exercise challenge performed 24 hours after a single oral dose

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

Arm	Measure	Value (MEAN)	Dispersion
Montelukast 10 mg	Maximum Percent Fall in FEV1 After Exercise Challenge at 24 Hours Post-dose in Patients With EIB	10.09 Percent Change from Baseline	Standard Deviation 11.1
Salmeterol 50-μg	Maximum Percent Fall in FEV1 After Exercise Challenge at 24 Hours Post-dose in Patients With EIB	16.22 Percent Change from Baseline	Standard Deviation 13.09
Placebo	Maximum Percent Fall in FEV1 After Exercise Challenge at 24 Hours Post-dose in Patients With EIB	13.64 Percent Change from Baseline	Standard Deviation 9.67

Secondary

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.

Time frame: 0-60 minutes after the exercise challenge performed 8.5 hours after a single oral dose

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

Arm	Measure	Value (MEAN)	Dispersion
Montelukast 10 mg	Maximum Percent Fall in FEV1 After Exercise Challenge at 8.5 Hours Post-dose in Patients With EIB	11.60 Percent Change from Baseline	Standard Deviation 9.64
Salmeterol 50-μg	Maximum Percent Fall in FEV1 After Exercise Challenge at 8.5 Hours Post-dose in Patients With EIB	11.01 Percent Change from Baseline	Standard Deviation 7.56
Placebo	Maximum Percent Fall in FEV1 After Exercise Challenge at 8.5 Hours Post-dose in Patients With EIB	16.65 Percent Change from Baseline	Standard Deviation 12.76

Secondary