Trial Outcomes & Findings for The Effect of Montelukast on Difficulty in Breathing After Exercise in Pediatric Patients (MK0476-377)(COMPLETED) (NCT NCT00534976)

Results Overview

Maximum Percent Fall in FEV1 was defined as the % change from pre-exercise baseline FEV1 to the lowest FEV1 within 60 mins (minutes) after exercise. Spirometry measurements were taken 5 mins prior to each exercise challenge and immediately, 5, 10, 15, 30, 45, \& 60 mins after each exercise challenge. The 2-hour exercise challenges occurred 2 hours after the witnessed dose of study medication. The calculation used to produce the results was \[100\*(1-(X/Y))\] where X= the lowest FEV1 within 60 mins after exercise \& Y= pre-exercise baseline FEV1. Smaller values mean greater response to therapy.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

364 participants

Primary outcome timeframe

Pre-exercise baseline and 0-60 minutes after the exercise challenge performed 2 hours post-dose

Results posted on

2024-05-13

Participant Flow

Of the 364 participants screened for inclusion, 298 participants were excluded during screening and were not randomized. The remaining 66 participants met inclusion criteria and were randomly allocated to one of the two treatment sequences.

Participant milestones

Participant milestones
Measure	Montelukast/ Placebo In Period I (screening period/ placebo run-in) participants received a single-blind dose of matching-image placebo. In Period II, participants 4-5 years of age were randomized to receive one Montelukast 4-mg chewable tablet (single dose). Period III was the crossover to one matching placebo 4-mg chewable tablet (single dose) after a 3- to 7-day washout period. No participants 4-5 years of age were randomized, so the 4-mg doses were not dispensed. Participants 6-14 years of age were randomized to receive one Montelukast 5-mg chewable tablet (single dose) in Period II, crossing over to one matching placebo 5-mg chewable tablet (single dose) in Period III after a 3- to 7-day washout period.	Placebo/ Montelukast In Period I (screening period/ placebo run-in) participants received a single-blind dose of matching-image placebo. In Period II, participants 4-5 years of age were randomized to receive one placebo 4-mg chewable tablet (single dose). Period III was the crossover to one Montelukast 4-mg chewable tablet (single dose) after a 3- to 7-day washout period. No participants 4-5 years of age were randomized, so the 4-mg doses were not dispensed. Participants 6-14 years of age were randomized to receive one placebo 5-mg chewable tablet (single dose) in Period II, crossing over to one Montelukast 5-mg chewable tablet (single dose) in Period III after a 3- to 7-day washout period.
Period 1: Placebo Run-in STARTED	33	33
Period 1: Placebo Run-in COMPLETED	33	33
Period 1: Placebo Run-in NOT COMPLETED	0	0
Period 2: Treatment Montelukast/ Placebo STARTED	33	33
Period 2: Treatment Montelukast/ Placebo COMPLETED	33	32
Period 2: Treatment Montelukast/ Placebo NOT COMPLETED	0	1
Period 3: Crossover Placebo/ Montelukast STARTED	33	32
Period 3: Crossover Placebo/ Montelukast COMPLETED	31	32
Period 3: Crossover Placebo/ Montelukast NOT COMPLETED	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Montelukast/ Placebo In Period I (screening period/ placebo run-in) participants received a single-blind dose of matching-image placebo. In Period II, participants 4-5 years of age were randomized to receive one Montelukast 4-mg chewable tablet (single dose). Period III was the crossover to one matching placebo 4-mg chewable tablet (single dose) after a 3- to 7-day washout period. No participants 4-5 years of age were randomized, so the 4-mg doses were not dispensed. Participants 6-14 years of age were randomized to receive one Montelukast 5-mg chewable tablet (single dose) in Period II, crossing over to one matching placebo 5-mg chewable tablet (single dose) in Period III after a 3- to 7-day washout period.	Placebo/ Montelukast In Period I (screening period/ placebo run-in) participants received a single-blind dose of matching-image placebo. In Period II, participants 4-5 years of age were randomized to receive one placebo 4-mg chewable tablet (single dose). Period III was the crossover to one Montelukast 4-mg chewable tablet (single dose) after a 3- to 7-day washout period. No participants 4-5 years of age were randomized, so the 4-mg doses were not dispensed. Participants 6-14 years of age were randomized to receive one placebo 5-mg chewable tablet (single dose) in Period II, crossing over to one Montelukast 5-mg chewable tablet (single dose) in Period III after a 3- to 7-day washout period.
Period 2: Treatment Montelukast/ Placebo Protocol Violation	0	1
Period 3: Crossover Placebo/ Montelukast Physician Decision	1	0
Period 3: Crossover Placebo/ Montelukast Withdrawal by Subject	1	0

Baseline Characteristics

The Effect of Montelukast on Difficulty in Breathing After Exercise in Pediatric Patients (MK0476-377)(COMPLETED)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Montelukast/ Placebo n=33 Participants In Period I (screening period/ placebo run-in) participants received a single-blind dose of matching-image placebo. In Period II, participants 4-5 years of age were randomized to receive one Montelukast 4-mg chewable tablet (single dose). Period III was the crossover to one matching placebo 4-mg chewable tablet (single dose) after a 3- to 7-day washout period. No participants 4-5 years of age were randomized, so the 4-mg doses were not dispensed. Participants 6-14 years of age were randomized to receive one Montelukast 5-mg chewable tablet (single dose) in Period II, crossing over to one matching placebo 5-mg chewable tablet (single dose) in Period III after a 3- to 7-day washout period.	Placebo/ Montelukast n=33 Participants In Period I (screening period/ placebo run-in) participants received a single-blind dose of matching-image placebo. In Period II, participants 4-5 years of age were randomized to receive one placebo 4-mg chewable tablet (single dose). Period III was the crossover to one Montelukast 4-mg chewable tablet (single dose) after a 3- to 7-day washout period. No participants 4-5 years of age were randomized, so the 4-mg doses were not dispensed. Participants 6-14 years of age were randomized to receive one placebo 5-mg chewable tablet (single dose) in Period II, crossing over to one Montelukast 5-mg chewable tablet (single dose) in Period III after a 3- to 7-day washout period.	Total n=66 Participants Total of all reporting groups
Age, Continuous	10.9 years STANDARD_DEVIATION 2.3 • n=5 Participants	11.5 years STANDARD_DEVIATION 1.8 • n=7 Participants	11.2 years STANDARD_DEVIATION 2.1 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	15 Participants n=7 Participants	29 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	18 Participants n=7 Participants	37 Participants n=5 Participants

PRIMARY outcome

Timeframe: Pre-exercise baseline and 0-60 minutes after the exercise challenge performed 2 hours post-dose

Population: The analysis of efficacy data was carried out using a completers analysis population. This population included all randomized patients who received the witnessed dose of study drug in both active treatment periods and had at least one post-exercise FEV1 measurement in both active treatment periods.

Maximum Percent Fall in FEV1 was defined as the % change from pre-exercise baseline FEV1 to the lowest FEV1 within 60 mins (minutes) after exercise. Spirometry measurements were taken 5 mins prior to each exercise challenge and immediately, 5, 10, 15, 30, 45, \& 60 mins after each exercise challenge. The 2-hour exercise challenges occurred 2 hours after the witnessed dose of study medication. The calculation used to produce the results was \[100\*(1-(X/Y))\] where X= the lowest FEV1 within 60 mins after exercise \& Y= pre-exercise baseline FEV1. Smaller values mean greater response to therapy.

Outcome measures

Outcome measures
Measure	Montelukast n=64 Participants In Period I (screening period/ placebo run-in) participants received a single-blind dose of matching-image placebo. Participants 6-14 years of age were randomized to receive one Montelukast 5-mg chewable tablet (single dose) in Period II or Period III, according to the randomized treatment sequence assigned. Period II and Period III were separated by a washout period of 3-7 days.	Placebo n=64 Participants In Period I (screening period/ placebo run-in) participants received a single-blind dose of matching-image placebo. Participants 6-14 years of age were randomized to receive one matching placebo 5-mg chewable tablet (single dose) in Period II or Period III, according to the randomized treatment sequence assigned. Period II and Period III were separated by a washout period of 3-7 days.
Maximum Percent Fall in Forced Expiratory Volume in 1 Second (FEV1) After Exercise Challenge at 2 Hours Postdose	15.35 Percent fall in FEV1 Standard Deviation 9.47 • Interval 12.6 to 18.11	20.00 Percent fall in FEV1 Standard Deviation 15.75 • Interval 17.25 to 22.76

SECONDARY outcome

Timeframe: Pre-exercise baseline and 0-60 minutes after the exercise challenge performed 24 hours post-dose

Population: The analysis of efficacy data was carried out using a completers analysis population. This population included all randomized patients who received the witnessed dose of study drug in both active treatment periods and had at least one post-exercise FEV1 measurement in both active treatment periods.

Maximum Percent Fall in FEV1 was defined as the % change from pre-exercise baseline FEV1 to the lowest FEV1 within 60 mins after exercise. Spirometry measurements were taken 5 mins prior to each exercise challenge and immediately, 5, 10, 15, 30, 45, \& 60 mins after each exercise challenge. The 24-hour exercise challenges occurred 20-24 hours after the witnessed dose of study medication. The calculation used to produce the resulted results was \[100\*(1-(X/Y))\] where X= the lowest FEV1 within 60 mins after exercise \& Y= pre-exercise baseline FEV1. Smaller values mean greater response to therapy.

Outcome measures

Outcome measures
Measure	Montelukast n=62 Participants In Period I (screening period/ placebo run-in) participants received a single-blind dose of matching-image placebo. Participants 6-14 years of age were randomized to receive one Montelukast 5-mg chewable tablet (single dose) in Period II or Period III, according to the randomized treatment sequence assigned. Period II and Period III were separated by a washout period of 3-7 days.	Placebo n=62 Participants In Period I (screening period/ placebo run-in) participants received a single-blind dose of matching-image placebo. Participants 6-14 years of age were randomized to receive one matching placebo 5-mg chewable tablet (single dose) in Period II or Period III, according to the randomized treatment sequence assigned. Period II and Period III were separated by a washout period of 3-7 days.
Maximum Percent Fall in FEV1 After Exercise Challenge at 24 Hours Post-dose	12.96 percent fall in FEV1 Standard Deviation 10.38 • Interval 10.81 to 15.04	17.22 percent fall in FEV1 Standard Deviation 12.06 • Interval 15.14 to 19.36

SECONDARY outcome

Timeframe: Pre-exercise baseline to 60 minutes after the exercise challenge performed 2 hours post-dose

Population: The analysis of efficacy data was carried out using a completers analysis population. This population included all randomized patients who received the witnessed dose of study drug in both active treatment periods and had at least one post-exercise FEV1 measurement in both active treatment periods.

AUC0-60min was defined as the Area Under the Curve for FEV1 percent change from pre-exercise baseline to the 60 mins following exercise challenge. The area was computed by applying the trapezoidal rule, and including only the area below the pre-exercise baseline. If a participant received β-agonist during the 60 mins after the exercise challenge, the FEV1 measurements obtained after β-agonist administration were excluded and the last pre-rescue FEV1 measurement was carried forward to the 60 mins time point in the calculation of the AUC0-60 min. Smaller values mean greater response to therapy.

Outcome measures

Outcome measures
Measure	Montelukast n=64 Participants In Period I (screening period/ placebo run-in) participants received a single-blind dose of matching-image placebo. Participants 6-14 years of age were randomized to receive one Montelukast 5-mg chewable tablet (single dose) in Period II or Period III, according to the randomized treatment sequence assigned. Period II and Period III were separated by a washout period of 3-7 days.	Placebo n=64 Participants In Period I (screening period/ placebo run-in) participants received a single-blind dose of matching-image placebo. Participants 6-14 years of age were randomized to receive one matching placebo 5-mg chewable tablet (single dose) in Period II or Period III, according to the randomized treatment sequence assigned. Period II and Period III were separated by a washout period of 3-7 days.
Area Under the Curve for FEV1 Percent Fall From Pre-exercise Baseline to 60 Minutes Following Exercise Challenge (AUC0-60 Min) at 2 Hours Post-dose	294.50 percent fall * minute Standard Deviation 278.46 • Interval 221.73 to 367.27	415.37 percent fall * minute Standard Deviation 375.94 • Interval 342.6 to 488.13

SECONDARY outcome

Timeframe: Pre-exercise baseline to 60 minutes after the exercise challenge performed 24 hours post-dose

Population: The analysis of efficacy data was carried out using a completers analysis population. This population included all randomized patients who received the witnessed dose of study drug in both active treatment periods and had at least one post-exercise FEV1 measurement in both active treatment periods.

AUC0-60min was defined as the Area Under the Curve for FEV1 percent change from pre-exercise baseline to the 60 mins following exercise challenge. The area was computed by applying the trapezoidal rule, and including only the area below the pre-exercise baseline. If a participant received β-agonist during the 60 mins after the exercise challenge, the FEV1 measurements obtained after β-agonist administration were excluded and the last pre-rescue FEV1 measurement was carried forward to the 60 mins time point in the calculation of the AUC0-60 min. Smaller values mean greater response to therapy.

Outcome measures

Outcome measures
Measure	Montelukast n=62 Participants In Period I (screening period/ placebo run-in) participants received a single-blind dose of matching-image placebo. Participants 6-14 years of age were randomized to receive one Montelukast 5-mg chewable tablet (single dose) in Period II or Period III, according to the randomized treatment sequence assigned. Period II and Period III were separated by a washout period of 3-7 days.	Placebo n=62 Participants In Period I (screening period/ placebo run-in) participants received a single-blind dose of matching-image placebo. Participants 6-14 years of age were randomized to receive one matching placebo 5-mg chewable tablet (single dose) in Period II or Period III, according to the randomized treatment sequence assigned. Period II and Period III were separated by a washout period of 3-7 days.
Area Under the Curve for FEV1 Percent Fall From Pre-exercise Baseline to 60 Minutes Following Exercise Challenge (AUC0-60 Min) at 24 Hours Post-dose	229.19 percent fall * minute Standard Deviation 233.93 • Interval 160.44 to 295.51	349.59 percent fall * minute Standard Deviation 315.29 • Interval 283.26 to 418.34

SECONDARY outcome

Timeframe: 0-60 minutes and 0-90 minutes after the exercise challenge at 2 hours postdose

Population: The analysis of efficacy data was carried out using a completers analysis population. This population included all randomized patients who received the witnessed dose of study drug in both active treatment periods and had at least one post-exercise FEV1 measurement in both active treatment periods.

This endpoint was defined as the duration between the time at which the maximum percent fall in FEV1 occurred \& the time when the percent fall in FEV1 returned to within 5% of the pre-exercise baseline for the first time. Spirometry measurements were taken 5 mins prior to each exercise challenge \& immediately, 5, 10, 15, 30, 45, \& 60 mins after each exercise challenge. If participant had not returned to within 5% of the pre-exercise FEV1 value by 60 mins, then measurements were obtained at 75 \& 90 mins. The 2-hour exercise challenges occurred 2 hours after the witnessed dose of medication.

Outcome measures

Outcome measures
Measure	Montelukast n=64 Participants In Period I (screening period/ placebo run-in) participants received a single-blind dose of matching-image placebo. Participants 6-14 years of age were randomized to receive one Montelukast 5-mg chewable tablet (single dose) in Period II or Period III, according to the randomized treatment sequence assigned. Period II and Period III were separated by a washout period of 3-7 days.	Placebo n=64 Participants In Period I (screening period/ placebo run-in) participants received a single-blind dose of matching-image placebo. Participants 6-14 years of age were randomized to receive one matching placebo 5-mg chewable tablet (single dose) in Period II or Period III, according to the randomized treatment sequence assigned. Period II and Period III were separated by a washout period of 3-7 days.
Time to Recovery From Maximum Percent Fall in FEV1 at 2 Hours Post-dose	16.21 Minutes Standard Deviation 22.01 • Interval 10.01 to 22.42	24.48 Minutes Standard Deviation 27.91 • Interval 18.27 to 30.68

SECONDARY outcome

Timeframe: 0-60 minutes and 0-90 minutes after the exercise challenge at 24 hours postdose

Population: The analysis of efficacy data was carried out using a completers analysis population. This population included all randomized patients who received the witnessed dose of study drug in both active treatment periods and had at least one post-exercise FEV1 measurement in both active treatment periods.

This endpoint was defined as the duration between the time at which the maximum percent fall in FEV1 occurred \& the time when the percent fall in FEV1 returned to within 5% of the pre-exercise baseline for the first time. Spirometry measurements were taken 5 mins prior to each exercise challenge \& immediately, 5, 10, 15, 30, 45 \& 60 mins after each exercise challenge. If participant had not returned to within 5% of the pre-exercise FEV1 value by 60 mins, then measurements were obtained at 75 \& 90 mins. The 24-hour exercise challenges occurred 20-24 hours after the witnessed dose of medication.

Outcome measures

Outcome measures
Measure	Montelukast n=62 Participants In Period I (screening period/ placebo run-in) participants received a single-blind dose of matching-image placebo. Participants 6-14 years of age were randomized to receive one Montelukast 5-mg chewable tablet (single dose) in Period II or Period III, according to the randomized treatment sequence assigned. Period II and Period III were separated by a washout period of 3-7 days.	Placebo n=62 Participants In Period I (screening period/ placebo run-in) participants received a single-blind dose of matching-image placebo. Participants 6-14 years of age were randomized to receive one matching placebo 5-mg chewable tablet (single dose) in Period II or Period III, according to the randomized treatment sequence assigned. Period II and Period III were separated by a washout period of 3-7 days.
Time to Recovery From Maximum Percent Fall in FEV1 at 24 Hours Post-dose	11.58 Minutes Standard Deviation 16.51 • Interval 6.42 to 16.56	18.46 Minutes Standard Deviation 22.66 • Interval 13.48 to 23.62

SECONDARY outcome

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

Population: The analysis of efficacy data was carried out using a completers analysis population. This population included all randomized patients who received the witnessed dose of study drug in both active treatment periods and had at least one post-exercise FEV1 measurement in both active treatment periods.

This endpoint was defined as the number of participants requiring rescue medication with β-agonist within the 90 mins following exercise challenge. The 2-hour exercise challenges occurred 2 hours after the witnessed dose of study medication.

Outcome measures

Outcome measures
Measure	Montelukast n=64 Participants In Period I (screening period/ placebo run-in) participants received a single-blind dose of matching-image placebo. Participants 6-14 years of age were randomized to receive one Montelukast 5-mg chewable tablet (single dose) in Period II or Period III, according to the randomized treatment sequence assigned. Period II and Period III were separated by a washout period of 3-7 days.	Placebo n=64 Participants In Period I (screening period/ placebo run-in) participants received a single-blind dose of matching-image placebo. Participants 6-14 years of age were randomized to receive one matching placebo 5-mg chewable tablet (single dose) in Period II or Period III, according to the randomized treatment sequence assigned. Period II and Period III were separated by a washout period of 3-7 days.
Number of Participants Requiring Rescue Medication at 2 Hours Postdose	1 participants Interval -9.27 to 5.63	2 participants

SECONDARY outcome

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

Population: The analysis of efficacy data was carried out using a completers analysis population. This population included all randomized patients who received the witnessed dose of study drug in both active treatment periods and had at least one post-exercise FEV1 measurement in both active treatment periods.

This endpoint was defined as the number of participants requiring rescue medication with β-agonist within the 90 mins following exercise challenge. The 24-hour exercise challenges occurred 20-24 hours after the witnessed dose of study medication.

Outcome measures

Outcome measures
Measure	Montelukast n=62 Participants In Period I (screening period/ placebo run-in) participants received a single-blind dose of matching-image placebo. Participants 6-14 years of age were randomized to receive one Montelukast 5-mg chewable tablet (single dose) in Period II or Period III, according to the randomized treatment sequence assigned. Period II and Period III were separated by a washout period of 3-7 days.	Placebo n=62 Participants In Period I (screening period/ placebo run-in) participants received a single-blind dose of matching-image placebo. Participants 6-14 years of age were randomized to receive one matching placebo 5-mg chewable tablet (single dose) in Period II or Period III, according to the randomized treatment sequence assigned. Period II and Period III were separated by a washout period of 3-7 days.
Number of Participants Requiring Rescue Medication at 24 Hours Postdose	0 Participants Interval -11.02 to 3.06	2 Participants

Adverse Events

Montelukast

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

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

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Subsequent to a multicenter publication, or 24 months after completion of the study, whichever comes first, an investigator may publish the results for their study site independently. However, the SPONSOR does not recommend separate publication of individual study site results. The SPONSOR must have the opportunity to review all proposed communications regarding this study 60 days prior to submission. Any information identified by the SPONSOR as confidential must be deleted.
Publication restrictions are in place

Restriction type: OTHER