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

A Phase III, Open-Label Clinical Trial to Study the Safety and Pharmacokinetics of MK-0476 in Japanese Pediatric Subjects Aged 1 to 15 Years Old With Perennial Allergic Rhinitis

This study will evaluate the safety and pharmacokinetics of montelukast (MK-0476) in the treatment of Japanese pediatric participants with perennial allergic rhinitis (PAR). The primary hypothesis of this study is that montelukast oral granules (OG) and chewable tablets (CT) provide appropriate exposure to montelukast in Japanese pediatric participants with PAR.

Study Overview

• Status: Completed
• Conditions: Perennial Allergic Rhinitis
• Intervention / Treatment: Drug: Montelukast Oral Granules (OG); Drug: Montelukast Chewable Tablets (CT)

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 15 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Weight ≥8 kg
• Diagnosis of PAR and has symptoms of PAR at Visit 1

Exclusion Criteria:

• Past or present medical history of asthma
• Diagosis of acute rhinitis, simple rhinitis, rhinitis congestive, rhinitis atrophic, sinusitis with purulent nasal discharge, rhinitis medicamentosa or nonallergic rhinitis (e.g. vasomotor rhinitis, eosinophilic rhinitis)
• Started hyposensitization therapy or non-specific immunotherapy within 6 months prior to Visit 1
• Medical history of inferior concha mucosal resection, submucous resection of inferior turbinates or other surgery aimed at reduction and/or modulation of nasal mucosa (including electrocoagulation, cryoextraction or application of trichloroacetic acid)
• Clinically significant, active disease of the cardiovascular or hematologic systems or uncontrolled hypertension (1 to 5 year olds: >120/70 mmHg; 6 to 9 year olds: >130/80 mmHg; 10 to 15 year olds: >140/85 mmHg)
• Medical history of stunted growth
• Serious drug allergy
• Treated with other clinical study drug within 3 months prior to Visit 1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Montelukast 4 mg OG/1-5 year olds; Participants receive montelukast 4 mg 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)	Drug: Montelukast Oral Granules (OG); Montelukast 4 mg in one sachet
EXPERIMENTAL: Montelukast 5 mg CT/6-9 year olds; Participants receive montelukast 5 mg CT in one tablet PO QD at bed time for 12 weeks	Drug: Montelukast Chewable Tablets (CT); Montelukast 5 mg in one tablet
EXPERIMENTAL: 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	Drug: Montelukast Chewable Tablets (CT); Montelukast 5 mg in one tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Experience at Least One Adverse Event (AE)	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.	Up to 14 days after last dose of study drug (Up to 14 weeks)
Percentage of Participants Who Discontinue Study Drug Due to an AE	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.	Up to 12 weeks
Area Under the Time-Concentration Curve (AUC 0-∞) of Montelukast CT and Montelukast OG	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.	Up to Day 28 after first dose of study drug
Maximum Plasma Concentration (Cmax) of Montelukast CT and Montelukast OG	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.	Up to Day 28 after first dose of study drug
Time to Cmax (Tmax) of Montelukast CT and Montelukast OG	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.	Up to Day 28 after first dose of study drug
Apparent Elimination Half-life (t1/2) of Montelukast CT and Montelukast OG	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.	Up to Day 28 after first dose of study drug

Collaborators and Investigators

• Sponsor: Organon and Co

Publications and helpful links

General Publications

• Okubo K, Inoue Y, Numaguchi H, Tanaka K, Saito I, Oshima N, Matsumoto Y, Prohn M, Mehta A, Nishida C, Philip G. Montelukast in the treatment of perennial allergic rhinitis in paediatric Japanese patients; an open-label clinical trial. J Drug Assess. 2016 Sep 19;5(1):6-14. doi: 10.1080/21556660.2016.1209507. eCollection 2016.
• Hashiguchi K, Okubo K, Inoue Y, Numaguchi H, Tanaka K, Oshima N, Mehta A, Nishida C, Saito I, Philip G. Evaluation of Montelukast for the Treatment of Children With Japanese Cedar Pollinosis Using an Artificial Exposure Chamber (OHIO Chamber). Allergy Rhinol (Providence). 2018 Jul 13;9:2152656718783599. doi: 10.1177/2152656718783599. eCollection 2018 Jan-Dec. Erratum In: Allergy Rhinol (Providence). 2018 Aug 22;9:2152656718797803.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 7, 2013
• Primary Completion (ACTUAL): December 24, 2013
• Study Completion (ACTUAL): December 24, 2013

Study Registration Dates

• First Submitted: May 9, 2013
• First Submitted That Met QC Criteria: May 9, 2013
• First Posted (ESTIMATE): May 14, 2013

Study Record Updates

• Last Update Posted (ACTUAL): February 9, 2022
• Last Update Submitted That Met QC Criteria: February 7, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Hypersensitivity, Immediate; Otorhinolaryngologic Diseases; Respiratory Hypersensitivity; Hypersensitivity; Nose Diseases; Rhinitis; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Asthmatic Agents; Respiratory System Agents; Leukotriene Antagonists; Hormone Antagonists; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers; Montelukast
• Other Study ID Numbers: 0476-520; 132233 (REGISTRY: JAPIC-CTI)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

1. CSR Synopsis