Trial Outcomes & Findings for Montelukast in Exercise-Induced Bronchospasm - 2003 (0476-270) (NCT NCT00092131)

NCT ID: NCT00092131

Last Updated: 2022-02-02

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 51 participants
• Primary outcome timeframe: Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed 2 hours after a single oral dose
• Results posted on: 2022-02-02

Participant Flow

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

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.

Participant milestones

Measure	Montelukast 10 mg in Period I Then Placebo in Period II A montelukast 10-mg tablet (Treatment Period I) was taken orally as a single witnessed dose followed by a 3-7 day washout. Then a montelukast matching-image placebo tablet (Treatment Period II) was taken orally as a single witnessed dose.	Placebo in Period I Then Montelukast 10 mg in Period II A montelukast matching-image placebo tablet (Treatment Period I) was taken orally as a single witnessed dose followed by a 3-7 day washout. Then a montelukast 10-mg tablet (Treatment Period II) was taken orally as a single witnessed dose.
Treatment Period I STARTED	25	26
Treatment Period I COMPLETED	24	26
Treatment Period I NOT COMPLETED	1	0
Treatment Period II STARTED	24	26
Treatment Period II COMPLETED	24	25
Treatment Period II NOT COMPLETED	0	1

Reasons for withdrawal

Measure	Montelukast 10 mg in Period I Then Placebo in Period II A montelukast 10-mg tablet (Treatment Period I) was taken orally as a single witnessed dose followed by a 3-7 day washout. Then a montelukast matching-image placebo tablet (Treatment Period II) was taken orally as a single witnessed dose.	Placebo in Period I Then Montelukast 10 mg in Period II A montelukast matching-image placebo tablet (Treatment Period I) was taken orally as a single witnessed dose followed by a 3-7 day washout. Then a montelukast 10-mg tablet (Treatment Period II) was taken orally as a single witnessed dose.
Treatment Period I Adverse Event	1	0
Treatment Period II Adverse Event	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Overall Study Population n=51 Participants All randomized patients
Age, Continuous	24.5 years STANDARD_DEVIATION 5.9 • n=5 Participants
Sex: Female, Male Female	27 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants
Need for β-agonist rescue medication following exercise challenge No	47 Participants n=5 Participants
Need for β-agonist rescue medication following exercise challenge Yes	4 Participants n=5 Participants
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 • n=5 Participants
Maximum Percent Fall in forced expiratory volume in 1 second (FEV1) post-exercise challenge	27.63 Percent change from pre-exercise measure STANDARD_DEVIATION 5.60 • n=5 Participants
Time to recovery from maximal percent fall in FEV1 after exercise challenge	45.15 Minutes STANDARD_DEVIATION 29.70 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Placebo n=49 Participants All Placebo patients from Treatment Periods I and II	Montelukast 10 mg n=49 Participants All Montelukast 10 mg patients from Treatment Periods I and II
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 13.10	10.80 Percent Change Standard Deviation 7.88

SECONDARY outcome

Timeframe: 0-90 minutes after the exercise challenge performed at 2 hours postdose

Population: 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.

Outcome measures

Measure	Placebo n=49 Participants All Placebo patients from Treatment Periods I and II	Montelukast 10 mg n=49 Participants All Montelukast 10 mg patients from Treatment Periods I and II
Number of Participants Requiring ß-Agonist Rescue Medication After Exercise Challenge at 2 Hours Postdose Number of Patients Requiring Rescue Medication	7 Participants	1 Participants
Number of Participants Requiring ß-Agonist Rescue Medication After Exercise Challenge at 2 Hours Postdose Number of Patients Not Requiring Rescue Medication	42 Participants	48 Participants

SECONDARY outcome

Timeframe: 0-90 minutes after the exercise challenge performed at 12 hours postdose

Population: 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.

Outcome measures

Measure	Placebo n=48 Participants All Placebo patients from Treatment Periods I and II	Montelukast 10 mg n=48 Participants All Montelukast 10 mg patients from Treatment Periods I and II
Number of Participants Requiring ß-Agonist Rescue Medication After Exercise Challenge at 12 Hours Postdose Number of Patients Requiring Rescue Medication	5 Participants	1 Participants
Number of Participants Requiring ß-Agonist Rescue Medication After Exercise Challenge at 12 Hours Postdose Number of Patients Not Requiring Rescue Medication	43 Participants	47 Participants

SECONDARY outcome

Timeframe: 0-90 minutes after the exercise challenge performed at 24 hours postdose

Population: 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.

Outcome measures

Measure	Placebo n=46 Participants All Placebo patients from Treatment Periods I and II	Montelukast 10 mg n=46 Participants All Montelukast 10 mg patients from Treatment Periods I and II
Number of Participants Requiring ß-Agonist Rescue Medication After Exercise Challenge at 24 Hours Postdose Number of Patients Requiring Rescue Medication	3 Participants	1 Participants
Number of Participants Requiring ß-Agonist Rescue Medication After Exercise Challenge at 24 Hours Postdose Number of Patients Not Requiring Rescue Medication	43 Participants	45 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Placebo n=48 Participants All Placebo patients from Treatment Periods I and II	Montelukast 10 mg n=48 Participants All Montelukast 10 mg patients from Treatment Periods I and II
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	8.35 Percent Change Standard Deviation 7.50

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Placebo n=46 Participants All Placebo patients from Treatment Periods I and II	Montelukast 10 mg n=46 Participants All Montelukast 10 mg patients from Treatment Periods I and II
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	8.33 Percent Change Standard Deviation 7.34

SECONDARY outcome

Timeframe: Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed at 2 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.

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

Outcome measures

Measure	Placebo n=49 Participants All Placebo patients from Treatment Periods I and II	Montelukast 10 mg n=49 Participants All Montelukast 10 mg patients from Treatment Periods I and II
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	182.46 (percent change) *minutes Standard Deviation 235.94

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Placebo n=48 Participants All Placebo patients from Treatment Periods I and II	Montelukast 10 mg n=48 Participants All Montelukast 10 mg patients from Treatment Periods I and II
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	152.27 (percent change) *minutes Standard Deviation 179.49

SECONDARY outcome

Timeframe: Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed 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.

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

Outcome measures

Measure	Placebo n=46 Participants All Placebo patients from Treatment Periods I and II	Montelukast 10 mg n=46 Participants All Montelukast 10 mg patients from Treatment Periods I and II
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	120.06 (percent change) *minutes Standard Deviation 119.77

SECONDARY outcome

Timeframe: Exercise challenge at 2 hours postdose

Population: 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.

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.

Outcome measures

Measure	Placebo n=49 Participants All Placebo patients from Treatment Periods I and II	Montelukast 10 mg n=49 Participants All Montelukast 10 mg patients from Treatment Periods I and II
Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 2 Hours Postdose	37.67 Minutes Standard Deviation 32.44	10.82 Minutes Standard Deviation 16.43

SECONDARY outcome

Timeframe: Exercise challenge at 12 hours postdose

Population: 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.

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.

Outcome measures

Measure	Placebo n=48 Participants All Placebo patients from Treatment Periods I and II	Montelukast 10 mg n=48 Participants All Montelukast 10 mg patients from Treatment Periods I and II
Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 12 Hours Postdose	24.50 Minutes Standard Deviation 25.71	7.97 Minutes Standard Deviation 12.68

SECONDARY outcome

Timeframe: Exercise challenge at 24 hours postdose

Population: 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.

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.

Outcome measures

Measure	Placebo n=46 Participants All Placebo patients from Treatment Periods I and II	Montelukast 10 mg n=46 Participants All Montelukast 10 mg patients from Treatment Periods I and II
Time to Recovery From Maximum Percentage Decrease in FEV1 After Exercise Challenge at 24 Hours Postdose	23.14 Minutes Standard Deviation 26.13	5.74 Minutes Standard Deviation 8.36

Adverse Events

Montelukast 10 mg in Period I Then Placebo in Period II

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo in Period I Then Montelukast 10 mg in Period II

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER