Trial Outcomes & Findings for Study of the Safety and Pharmacokinetics of Montelukast (MK-0476) in the Treatment of Japanese Pediatric Participants With Perennial Allergic Rhinitis (MK-0476-520) (NCT NCT01852812)

Last Updated: 2024-06-18

Results Overview

An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of study drug or protocol-specified procedure, whether or not considered related to the study drug or protocol-specified procedure. Any worsening of a pre-existing condition that is temporally associated with the use of study drug is also an AE. Participants were monitored for the occurrence of AEs for up to 14 days after last dose of study drug (up to a total of 14 weeks). AEs were reported based on the dose of study drug participants received.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

87 participants

Primary outcome timeframe

Up to 14 days after last dose of study drug (Up to 14 weeks)

Results posted on

2024-06-18

Participant Flow

Participant milestones

Participant milestones
Measure	Montelukast 4 mg OG/1-5 Year Olds Participants receive montelukast 4 mg oral granules (OG) in one sachet orally (PO) once daily (QD) at bed time for 4 weeks with an option to continue for an additional 8 weeks (12 weeks total)	Montelukast 5 mg CT/6-9 Year Olds Participants receive montelukast 5 mg chewable tablets (CT) in one tablet PO QD at bed time for 12 weeks	Montelukast 5 mg CT/10-15 Year Olds Participants receive montelukast 5 mg CT in one tablet PO QD at bed time for 12 weeks
Overall Study STARTED	51	18	18
Overall Study COMPLETED	51	17	17
Overall Study NOT COMPLETED	0	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Montelukast 4 mg OG/1-5 Year Olds Participants receive montelukast 4 mg oral granules (OG) in one sachet orally (PO) once daily (QD) at bed time for 4 weeks with an option to continue for an additional 8 weeks (12 weeks total)	Montelukast 5 mg CT/6-9 Year Olds Participants receive montelukast 5 mg chewable tablets (CT) in one tablet PO QD at bed time for 12 weeks	Montelukast 5 mg CT/10-15 Year Olds Participants receive montelukast 5 mg CT in one tablet PO QD at bed time for 12 weeks
Overall Study Adverse Event	0	0	1
Overall Study Non-compliance With Study Drug	0	1	0

Baseline Characteristics

Study of the Safety and Pharmacokinetics of Montelukast (MK-0476) in the Treatment of Japanese Pediatric Participants With Perennial Allergic Rhinitis (MK-0476-520)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Montelukast 4 mg OG/1-5 Year Olds n=51 Participants Participants receive montelukast 4 mg OG in one sachet PO QD at bed time for 4 weeks with an option to continue for an additional 8 weeks (12 weeks total)	Montelukast 5 mg CT/6-9 Year Olds n=18 Participants Participants receive montelukast 5 mg CT in one tablet PO QD at bed time for 12 weeks	Montelukast 5 mg CT/10-15 Year Olds n=18 Participants Participants receive montelukast 5 mg CT in one tablet PO QD at bed time for 12 weeks	Total n=87 Participants Total of all reporting groups
Age, Continuous	3.61 Years STANDARD_DEVIATION 1.4 • n=5 Participants	7.78 Years STANDARD_DEVIATION 1.3 • n=7 Participants	11.3 Years STANDARD_DEVIATION 1.0 • n=5 Participants	6.07 Years STANDARD_DEVIATION 3.4 • n=4 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	8 Participants n=7 Participants	5 Participants n=5 Participants	37 Participants n=4 Participants
Sex: Female, Male Male	27 Participants n=5 Participants	10 Participants n=7 Participants	13 Participants n=5 Participants	50 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 14 days after last dose of study drug (Up to 14 weeks)

Population: The All Subjects as Treated (ASaT) population consisted of all participants who received at least one dose of study drug. Data from the two montelukast 5 mg CT groups (6-9 year olds and 10-15 year olds) were pooled for safety analyses.

Outcome measures

Outcome measures
Measure	Montelukast 4 mg OG/1-5 Year Olds n=51 Participants Participants receive montelukast 4 mg OG in one sachet PO QD at bed time for 4 weeks with an option to continue for an additional 8 weeks (12 weeks total)	Montelukast 5 mg CT/6-15 Year Olds n=36 Participants Participants receive montelukast 5 mg CT in one tablet PO QD at bed time for 12 weeks	Montelukast 5 mg CT/10-15 Year Olds Participants receive montelukast 5 mg CT in one tablet PO QD at bed time for 12 weeks
Percentage of Participants Who Experience at Least One Adverse Event (AE)	74.5 Percentage of participants	55.6 Percentage of participants	—

PRIMARY outcome

Timeframe: Up to 12 weeks

Population: The ASaT population consisted of all participants who received at least one dose of study drug. Data from the two montelukast 5 mg CT groups (6-9 year olds and 10-15 year olds) were pooled for safety analyses.

An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of study drug or protocol-specified procedure, whether or not considered related to the study drug or protocol-specified procedure. Any worsening of a pre-existing condition that is temporally associated with the use of study drug is also an AE. Discontinuations due to an AE were reported based on the dose of study drug participants received.

Outcome measures

Outcome measures
Measure	Montelukast 4 mg OG/1-5 Year Olds n=51 Participants Participants receive montelukast 4 mg OG in one sachet PO QD at bed time for 4 weeks with an option to continue for an additional 8 weeks (12 weeks total)	Montelukast 5 mg CT/6-15 Year Olds n=36 Participants Participants receive montelukast 5 mg CT in one tablet PO QD at bed time for 12 weeks	Montelukast 5 mg CT/10-15 Year Olds Participants receive montelukast 5 mg CT in one tablet PO QD at bed time for 12 weeks
Percentage of Participants Who Discontinue Study Drug Due to an AE	0.0 Percentage of participants	2.8 Percentage of participants	—

PRIMARY outcome

Timeframe: Up to Day 28 after first dose of study drug

Population: The All Subjects Pharmacokinetically Evaluable (ASPE) population consisted of all participants from the ASaT population who had an evaluable assessement for this PK parameter and did not have any protocol violation which would interfere with this PK parameter. Data for PK assessments were reported by dose of study drug received and age group.

Blood samples for pharmacokinetic (PK) assessments were collected at either 1 hour (h) or 3 h post-dose on Day 1 and at either 14 h or 22 h post-dose on Day 28.

Outcome measures

Outcome measures
Measure	Montelukast 4 mg OG/1-5 Year Olds n=51 Participants Participants receive montelukast 4 mg OG in one sachet PO QD at bed time for 4 weeks with an option to continue for an additional 8 weeks (12 weeks total)	Montelukast 5 mg CT/6-15 Year Olds n=18 Participants Participants receive montelukast 5 mg CT in one tablet PO QD at bed time for 12 weeks	Montelukast 5 mg CT/10-15 Year Olds n=18 Participants Participants receive montelukast 5 mg CT in one tablet PO QD at bed time for 12 weeks
Area Under the Time-Concentration Curve (AUC 0-∞) of Montelukast CT and Montelukast OG	4300 h*ng/mL Standard Deviation 800	4350 h*ng/mL Standard Deviation 760	3500 h*ng/mL Standard Deviation 620

PRIMARY outcome

Timeframe: Up to Day 28 after first dose of study drug

Population: The ASPE population consisted of all participants from the ASaT population who had an evaluable assessement for this PK parameter and did not have any protocol violation which would interfere with this PK parameter. Data for PK assessments were reported by dose of study drug received and age group.

Blood samples for PK assessments were collected at either 1 h or 3 h post-dose on Day 1 and at either 14 h or 22 h post-dose on Day 28.

Outcome measures

Outcome measures
Measure	Montelukast 4 mg OG/1-5 Year Olds n=51 Participants Participants receive montelukast 4 mg OG in one sachet PO QD at bed time for 4 weeks with an option to continue for an additional 8 weeks (12 weeks total)	Montelukast 5 mg CT/6-15 Year Olds n=18 Participants Participants receive montelukast 5 mg CT in one tablet PO QD at bed time for 12 weeks	Montelukast 5 mg CT/10-15 Year Olds n=18 Participants Participants receive montelukast 5 mg CT in one tablet PO QD at bed time for 12 weeks
Maximum Plasma Concentration (Cmax) of Montelukast CT and Montelukast OG	510 ng/mL Standard Deviation 84	438 ng/mL Standard Deviation 82	344 ng/mL Standard Deviation 61

PRIMARY outcome

Timeframe: Up to Day 28 after first dose of study drug

Blood samples for PK assessments were collected at either 1 h or 3 h post-dose on Day 1 and at either 14 h or 22 h post-dose on Day 28.

Outcome measures

Outcome measures
Measure	Montelukast 4 mg OG/1-5 Year Olds n=51 Participants Participants receive montelukast 4 mg OG in one sachet PO QD at bed time for 4 weeks with an option to continue for an additional 8 weeks (12 weeks total)	Montelukast 5 mg CT/6-15 Year Olds n=18 Participants Participants receive montelukast 5 mg CT in one tablet PO QD at bed time for 12 weeks	Montelukast 5 mg CT/10-15 Year Olds n=18 Participants Participants receive montelukast 5 mg CT in one tablet PO QD at bed time for 12 weeks
Time to Cmax (Tmax) of Montelukast CT and Montelukast OG	2.74 Hours Standard Deviation 0.60	3.55 Hours Standard Deviation 0.71	3.65 Hours Standard Deviation 0.60

PRIMARY outcome

Timeframe: Up to Day 28 after first dose of study drug

Blood samples for PK assessments were collected at either 1 h or 3 h post-dose on Day 1 and at either 14 h or 22 h post-dose on Day 28.

Outcome measures

Outcome measures
Measure	Montelukast 4 mg OG/1-5 Year Olds n=51 Participants Participants receive montelukast 4 mg OG in one sachet PO QD at bed time for 4 weeks with an option to continue for an additional 8 weeks (12 weeks total)	Montelukast 5 mg CT/6-15 Year Olds n=18 Participants Participants receive montelukast 5 mg CT in one tablet PO QD at bed time for 12 weeks	Montelukast 5 mg CT/10-15 Year Olds n=18 Participants Participants receive montelukast 5 mg CT in one tablet PO QD at bed time for 12 weeks
Apparent Elimination Half-life (t1/2) of Montelukast CT and Montelukast OG	1.27 Hours Standard Deviation 0.56	2.01 Hours Standard Deviation 0.75	2.08 Hours Standard Deviation 0.66

Adverse Events

Montelukast 4 mg OG/1-5 Year Olds

Serious events: 0 serious events

Other events: 37 other events

Deaths: 0 deaths

Montelukast 5 mg CT/6-15 Year Olds

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Montelukast 4 mg OG/1-5 Year Olds n=51 participants at risk Participants receive montelukast 4 mg OG in one sachet PO QD at bed time for 4 weeks with an option to continue for an additional 8 weeks (12 weeks total)	Montelukast 5 mg CT/6-15 Year Olds n=36 participants at risk Participants receive montelukast 5 mg CT in one tablet PO QD at bed time for 12 weeks
Gastrointestinal disorders Diarrhoea	7.8% 4/51 • Number of events 4 • Up to 14 days after last dose of study drug (Up to 14 weeks) The ASaT population consisted of all participants who received at least one dose of study drug. AEs were reported based on the dose of study drug participants received. Data from the two montelukast 5 mg CT groups (6-9 year olds and 10-15 year olds) were pooled for safety analyses.	0.00% 0/36 • Up to 14 days after last dose of study drug (Up to 14 weeks) The ASaT population consisted of all participants who received at least one dose of study drug. AEs were reported based on the dose of study drug participants received. Data from the two montelukast 5 mg CT groups (6-9 year olds and 10-15 year olds) were pooled for safety analyses.
Infections and infestations Acute sinusitis	11.8% 6/51 • Number of events 8 • Up to 14 days after last dose of study drug (Up to 14 weeks) The ASaT population consisted of all participants who received at least one dose of study drug. AEs were reported based on the dose of study drug participants received. Data from the two montelukast 5 mg CT groups (6-9 year olds and 10-15 year olds) were pooled for safety analyses.	0.00% 0/36 • Up to 14 days after last dose of study drug (Up to 14 weeks) The ASaT population consisted of all participants who received at least one dose of study drug. AEs were reported based on the dose of study drug participants received. Data from the two montelukast 5 mg CT groups (6-9 year olds and 10-15 year olds) were pooled for safety analyses.
Infections and infestations Bronchitis	5.9% 3/51 • Number of events 4 • Up to 14 days after last dose of study drug (Up to 14 weeks) The ASaT population consisted of all participants who received at least one dose of study drug. AEs were reported based on the dose of study drug participants received. Data from the two montelukast 5 mg CT groups (6-9 year olds and 10-15 year olds) were pooled for safety analyses.	8.3% 3/36 • Number of events 3 • Up to 14 days after last dose of study drug (Up to 14 weeks) The ASaT population consisted of all participants who received at least one dose of study drug. AEs were reported based on the dose of study drug participants received. Data from the two montelukast 5 mg CT groups (6-9 year olds and 10-15 year olds) were pooled for safety analyses.
Infections and infestations Gastroenteritis	5.9% 3/51 • Number of events 3 • Up to 14 days after last dose of study drug (Up to 14 weeks) The ASaT population consisted of all participants who received at least one dose of study drug. AEs were reported based on the dose of study drug participants received. Data from the two montelukast 5 mg CT groups (6-9 year olds and 10-15 year olds) were pooled for safety analyses.	2.8% 1/36 • Number of events 1 • Up to 14 days after last dose of study drug (Up to 14 weeks) The ASaT population consisted of all participants who received at least one dose of study drug. AEs were reported based on the dose of study drug participants received. Data from the two montelukast 5 mg CT groups (6-9 year olds and 10-15 year olds) were pooled for safety analyses.
Infections and infestations Hand-foot-and-mouth disease	5.9% 3/51 • Number of events 3 • Up to 14 days after last dose of study drug (Up to 14 weeks) The ASaT population consisted of all participants who received at least one dose of study drug. AEs were reported based on the dose of study drug participants received. Data from the two montelukast 5 mg CT groups (6-9 year olds and 10-15 year olds) were pooled for safety analyses.	0.00% 0/36 • Up to 14 days after last dose of study drug (Up to 14 weeks) The ASaT population consisted of all participants who received at least one dose of study drug. AEs were reported based on the dose of study drug participants received. Data from the two montelukast 5 mg CT groups (6-9 year olds and 10-15 year olds) were pooled for safety analyses.
Infections and infestations Nasopharyngitis	43.1% 22/51 • Number of events 32 • Up to 14 days after last dose of study drug (Up to 14 weeks) The ASaT population consisted of all participants who received at least one dose of study drug. AEs were reported based on the dose of study drug participants received. Data from the two montelukast 5 mg CT groups (6-9 year olds and 10-15 year olds) were pooled for safety analyses.	33.3% 12/36 • Number of events 15 • Up to 14 days after last dose of study drug (Up to 14 weeks) The ASaT population consisted of all participants who received at least one dose of study drug. AEs were reported based on the dose of study drug participants received. Data from the two montelukast 5 mg CT groups (6-9 year olds and 10-15 year olds) were pooled for safety analyses.
Infections and infestations Otitis media	7.8% 4/51 • Number of events 4 • Up to 14 days after last dose of study drug (Up to 14 weeks) The ASaT population consisted of all participants who received at least one dose of study drug. AEs were reported based on the dose of study drug participants received. Data from the two montelukast 5 mg CT groups (6-9 year olds and 10-15 year olds) were pooled for safety analyses.	2.8% 1/36 • Number of events 1 • Up to 14 days after last dose of study drug (Up to 14 weeks) The ASaT population consisted of all participants who received at least one dose of study drug. AEs were reported based on the dose of study drug participants received. Data from the two montelukast 5 mg CT groups (6-9 year olds and 10-15 year olds) were pooled for safety analyses.
Infections and infestations Otitis media acute	5.9% 3/51 • Number of events 4 • Up to 14 days after last dose of study drug (Up to 14 weeks) The ASaT population consisted of all participants who received at least one dose of study drug. AEs were reported based on the dose of study drug participants received. Data from the two montelukast 5 mg CT groups (6-9 year olds and 10-15 year olds) were pooled for safety analyses.	0.00% 0/36 • Up to 14 days after last dose of study drug (Up to 14 weeks) The ASaT population consisted of all participants who received at least one dose of study drug. AEs were reported based on the dose of study drug participants received. Data from the two montelukast 5 mg CT groups (6-9 year olds and 10-15 year olds) were pooled for safety analyses.
Infections and infestations Pharyngitis	17.6% 9/51 • Number of events 14 • Up to 14 days after last dose of study drug (Up to 14 weeks) The ASaT population consisted of all participants who received at least one dose of study drug. AEs were reported based on the dose of study drug participants received. Data from the two montelukast 5 mg CT groups (6-9 year olds and 10-15 year olds) were pooled for safety analyses.	8.3% 3/36 • Number of events 4 • Up to 14 days after last dose of study drug (Up to 14 weeks) The ASaT population consisted of all participants who received at least one dose of study drug. AEs were reported based on the dose of study drug participants received. Data from the two montelukast 5 mg CT groups (6-9 year olds and 10-15 year olds) were pooled for safety analyses.
Injury, poisoning and procedural complications Arthropod sting	3.9% 2/51 • Number of events 2 • Up to 14 days after last dose of study drug (Up to 14 weeks) The ASaT population consisted of all participants who received at least one dose of study drug. AEs were reported based on the dose of study drug participants received. Data from the two montelukast 5 mg CT groups (6-9 year olds and 10-15 year olds) were pooled for safety analyses.	5.6% 2/36 • Number of events 4 • Up to 14 days after last dose of study drug (Up to 14 weeks) The ASaT population consisted of all participants who received at least one dose of study drug. AEs were reported based on the dose of study drug participants received. Data from the two montelukast 5 mg CT groups (6-9 year olds and 10-15 year olds) were pooled for safety analyses.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/51 • Up to 14 days after last dose of study drug (Up to 14 weeks) The ASaT population consisted of all participants who received at least one dose of study drug. AEs were reported based on the dose of study drug participants received. Data from the two montelukast 5 mg CT groups (6-9 year olds and 10-15 year olds) were pooled for safety analyses.	5.6% 2/36 • Number of events 2 • Up to 14 days after last dose of study drug (Up to 14 weeks) The ASaT population consisted of all participants who received at least one dose of study drug. AEs were reported based on the dose of study drug participants received. Data from the two montelukast 5 mg CT groups (6-9 year olds and 10-15 year olds) were pooled for safety analyses.
Skin and subcutaneous tissue disorders Miliaria	0.00% 0/51 • Up to 14 days after last dose of study drug (Up to 14 weeks) The ASaT population consisted of all participants who received at least one dose of study drug. AEs were reported based on the dose of study drug participants received. Data from the two montelukast 5 mg CT groups (6-9 year olds and 10-15 year olds) were pooled for safety analyses.	5.6% 2/36 • Number of events 2 • Up to 14 days after last dose of study drug (Up to 14 weeks) The ASaT population consisted of all participants who received at least one dose of study drug. AEs were reported based on the dose of study drug participants received. Data from the two montelukast 5 mg CT groups (6-9 year olds and 10-15 year olds) were pooled for safety analyses.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation.
Publication restrictions are in place

Restriction type: OTHER