Trial Outcomes & Findings for Montelukast in Exercise-Induced Bronchospasm - 2004 (0476-275) (NCT NCT00090142)
NCT ID: NCT00090142
Last Updated: 2022-02-02
Results Overview
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.
COMPLETED
PHASE3
62 participants
Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed 2 hours after a single oral dose
2022-02-02
Participant Flow
Patients were randomized at 8 sites (7 in the US and 1 in Peru). Primary therapy period: May to October 2004.
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.
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 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.
|
Placebo in Period I Then Montelukast 10 mg in Period II
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.
|
|---|---|---|
|
Treatment Period I
STARTED
|
31
|
31
|
|
Treatment Period I
COMPLETED
|
26
|
28
|
|
Treatment Period I
NOT COMPLETED
|
5
|
3
|
|
Treatment Period II
STARTED
|
26
|
28
|
|
Treatment Period II
COMPLETED
|
25
|
28
|
|
Treatment Period II
NOT COMPLETED
|
1
|
0
|
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 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.
|
Placebo in Period I Then Montelukast 10 mg in Period II
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.
|
|---|---|---|
|
Treatment Period I
Lost to Follow-up
|
1
|
2
|
|
Treatment Period I
Protocol Violation
|
2
|
0
|
|
Treatment Period I
Withdrawal by Subject
|
2
|
0
|
|
Treatment Period I
Other
|
0
|
1
|
|
Treatment Period II
Other
|
1
|
0
|
Baseline Characteristics
Montelukast in Exercise-Induced Bronchospasm - 2004 (0476-275)
Baseline characteristics by cohort
| Measure |
Overall Study Population
n=62 Participants
All randomized patients
|
|---|---|
|
Age, Continuous
|
24.4 years
STANDARD_DEVIATION 6.9 • n=99 Participants
|
|
Sex: Female, Male
Female
|
29 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
33 Participants
n=99 Participants
|
|
Need for β-agonist rescue medication following exercise challenge
No
|
47 Participants
n=99 Participants
|
|
Need for β-agonist rescue medication following exercise challenge
Yes
|
15 Participants
n=99 Participants
|
|
AUC for percent change from pre-exercise measurement FEV1 in L 0-60 mins after exercise challenge
|
815.27 (percent change) *minutes
STANDARD_DEVIATION 516.83 • n=99 Participants
|
|
Maximum percent fall in Forced Expiratory Volume in 1 second (FEV1) post-exercise challenge
|
26.86 percent change from pre-exercise measure
STANDARD_DEVIATION 7.04 • n=99 Participants
|
|
Time to recovery from maximal percent fall
|
44.73 Minutes
STANDARD_DEVIATION 32.23 • n=99 Participants
|
PRIMARY outcome
Timeframe: Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed 2 hours after a single oral dosePopulation: 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.
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.
Outcome measures
| Measure |
Placebo
n=54 Participants
All Placebo patients from Treatment Periods I and II
|
Montelukast 10 mg
n=54 Participants
All Montelukast 10 mg patients from Treatment Periods I and II
|
|---|---|---|
|
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)
|
17.50 Percent Change
Standard Deviation 13.82
|
11.70 Percent Change
Standard Deviation 10.80
|
SECONDARY outcome
Timeframe: 0-90 minutes after the exercise challenge performed at 2 hours postdosePopulation: 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=54 Participants
All Placebo patients from Treatment Periods I and II
|
Montelukast 10 mg
n=54 Participants
All Montelukast 10 mg patients from Treatment Periods I and II
|
|---|---|---|
|
Number of Patients Requiring ß-Agonist Rescue Medication After Exercise Challenge at 2 Hours Postdose
Patients requiring rescue medication
|
7 Participants
|
2 Participants
|
|
Number of Patients Requiring ß-Agonist Rescue Medication After Exercise Challenge at 2 Hours Postdose
Patients not requiring rescue medication
|
47 Participants
|
52 Participants
|
SECONDARY outcome
Timeframe: 0-90 minutes after the exercise challenge performed at 12 hours postdosePopulation: 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=52 Participants
All Placebo patients from Treatment Periods I and II
|
Montelukast 10 mg
n=52 Participants
All Montelukast 10 mg patients from Treatment Periods I and II
|
|---|---|---|
|
Number of Patients Requiring ß-Agonist Rescue Medication After Exercise Challenge at 12 Hours Postdose
Patients requiring rescue medication
|
4 Participants
|
2 Participants
|
|
Number of Patients Requiring ß-Agonist Rescue Medication After Exercise Challenge at 12 Hours Postdose
Patients not requiring rescue medication
|
48 Participants
|
50 Participants
|
SECONDARY outcome
Timeframe: 0-90 minutes after the exercise challenge performed at 24 hours postdosePopulation: 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=52 Participants
All Placebo patients from Treatment Periods I and II
|
Montelukast 10 mg
n=52 Participants
All Montelukast 10 mg patients from Treatment Periods I and II
|
|---|---|---|
|
Number of Patients Requiring ß-Agonist Rescue Medication After Exercise Challenge at 24 Hours Postdose
Patients requiring rescue medication
|
2 Participants
|
2 Participants
|
|
Number of Patients Requiring ß-Agonist Rescue Medication After Exercise Challenge at 24 Hours Postdose
Patients not requiring rescue medication
|
50 Participants
|
50 Participants
|
SECONDARY outcome
Timeframe: Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed 12 hours after a single oral dosePopulation: 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.
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.
Outcome measures
| Measure |
Placebo
n=52 Participants
All Placebo patients from Treatment Periods I and II
|
Montelukast 10 mg
n=52 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 EIB
|
11.73 Percent Change
Standard Deviation 11.64
|
9.87 Percent Change
Standard Deviation 11.43
|
SECONDARY outcome
Timeframe: Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed 24 hours after a single oral dosePopulation: 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.
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.
Outcome measures
| Measure |
Placebo
n=52 Participants
All Placebo patients from Treatment Periods I and II
|
Montelukast 10 mg
n=52 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 EIB
|
10.69 Percent Change
Standard Deviation 12.31
|
7.95 Percent Change
Standard Deviation 10.80
|
SECONDARY outcome
Timeframe: Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed at 2 hours postdosePopulation: 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=54 Participants
All Placebo patients from Treatment Periods I and II
|
Montelukast 10 mg
n=54 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 0-60 Min) at 2 Hours Postdose
|
582.6 (percent change) *minutes
Standard Deviation 759.1
|
284.7 (percent change) *minutes
Standard Deviation 426.9
|
SECONDARY outcome
Timeframe: Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed at 12 hours postdosePopulation: 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=52 Participants
All Placebo patients from Treatment Periods I and II
|
Montelukast 10 mg
n=52 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 0-60 Min) at 12 Hours Postdose
|
314.0 (percent change) *minutes
Standard Deviation 417.7
|
241.7 (percent change) *minutes
Standard Deviation 545.9
|
SECONDARY outcome
Timeframe: Pre-exercise baseline measurement and 0-60 minutes after the exercise challenge performed at 24 hours postdosePopulation: 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.
The measure included only the area below the pre-exercise baseline.
Outcome measures
| Measure |
Placebo
n=52 Participants
All Placebo patients from Treatment Periods I and II
|
Montelukast 10 mg
n=52 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
|
269.6 (percent change) *minutes
Standard Deviation 507.8
|
223.1 (percent change) *minutes
Standard Deviation 527.1
|
SECONDARY outcome
Timeframe: Exercise challenge at 2 hours postdosePopulation: 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 after exercise challenge occurs and the time when FEV1 returns to within 5% of the preexercise baseline for the first time.
Outcome measures
| Measure |
Placebo
n=54 Participants
All Placebo patients from Treatment Periods I and II
|
Montelukast 10 mg
n=54 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
|
34.23 Minutes
Standard Deviation 36.01
|
15.87 Minutes
Standard Deviation 25.29
|
SECONDARY outcome
Timeframe: Exercise challenge at 12 hours postdosePopulation: 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 after exercise challenge occurs and the time when FEV1 returns to within 5% of the preexercise baseline for the first time.
Outcome measures
| Measure |
Placebo
n=52 Participants
All Placebo patients from Treatment Periods I and II
|
Montelukast 10 mg
n=52 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
|
23.40 Minutes
Standard Deviation 32.20
|
9.42 Minutes
Standard Deviation 18.27
|
SECONDARY outcome
Timeframe: Exercise challenge at 24 hours postdosePopulation: 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 after exercise challenge occurs and the time when FEV1 returns to within 5% of the preexercise baseline for the first time.
Outcome measures
| Measure |
Placebo
n=52 Participants
All Placebo patients from Treatment Periods I and II
|
Montelukast 10 mg
n=52 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
|
13.81 Minutes
Standard Deviation 22.80
|
9.47 Minutes
Standard Deviation 19.52
|
Adverse Events
Montelukast 10 mg
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Montelukast 10 mg
n=58 participants at risk
|
Placebo
n=57 participants at risk
|
|---|---|---|
|
Nervous system disorders
Headache
|
1.7%
1/58 • 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
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.
|
5.3%
3/57 • 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
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.
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp
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