Perennial Allergic Rhinitis
Conditions
Brief summary
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.
Interventions
DRUGMontelukast Oral Granules (OG)
Montelukast 4 mg in one sachet
DRUGMontelukast Chewable Tablets (CT)
Montelukast 5 mg in one tablet
Sponsors
Organon and Co
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 15 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experience at Least One Adverse Event (AE) | Up to 14 days after last dose of study drug (Up to 14 weeks) | 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. |
| Percentage of Participants Who Discontinue Study Drug Due to an AE | Up to 12 weeks | 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. |
| Area Under the Time-Concentration Curve (AUC 0-∞) of Montelukast CT and Montelukast OG | Up to Day 28 after first dose of study drug | 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. |
| Maximum Plasma Concentration (Cmax) of Montelukast CT and Montelukast OG | 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. |
| Time to Cmax (Tmax) of Montelukast CT and Montelukast OG | 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. |
| Apparent Elimination Half-life (t1/2) of Montelukast CT and Montelukast OG | 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. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Montelukast 4 mg OG/1-5 Year Olds 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) | 51 |
| 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 | 18 |
| 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 | 18 |
| Total | 87 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 |
| Overall Study | Non-compliance With Study Drug | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Montelukast 4 mg OG/1-5 Year Olds | Montelukast 5 mg CT/6-9 Year Olds | Montelukast 5 mg CT/10-15 Year Olds | Total |
|---|---|---|---|---|
| Age, Continuous | 3.61 Years STANDARD_DEVIATION 1.4 | 7.78 Years STANDARD_DEVIATION 1.3 | 11.3 Years STANDARD_DEVIATION 1 | 6.07 Years STANDARD_DEVIATION 3.4 |
| Sex: Female, Male Female | 24 Participants | 8 Participants | 5 Participants | 37 Participants |
| Sex: Female, Male Male | 27 Participants | 10 Participants | 13 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 37 / 51 | 18 / 36 |
| serious Total, serious adverse events | 0 / 51 | 0 / 36 |
Outcome results
Primary
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Montelukast 4 mg OG/1-5 Year Olds | Apparent Elimination Half-life (t1/2) of Montelukast CT and Montelukast OG | 1.27 Hours | Standard Deviation 0.56 |
| Montelukast 5 mg CT/6-15 Year Olds | Apparent Elimination Half-life (t1/2) of Montelukast CT and Montelukast OG | 2.01 Hours | Standard Deviation 0.75 |
| Montelukast 5 mg CT/10-15 Year Olds | Apparent Elimination Half-life (t1/2) of Montelukast CT and Montelukast OG | 2.08 Hours | Standard Deviation 0.66 |
Primary
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Montelukast 4 mg OG/1-5 Year Olds | Area Under the Time-Concentration Curve (AUC 0-∞) of Montelukast CT and Montelukast OG | 4300 h*ng/mL | Standard Deviation 800 |
| Montelukast 5 mg CT/6-15 Year Olds | Area Under the Time-Concentration Curve (AUC 0-∞) of Montelukast CT and Montelukast OG | 4350 h*ng/mL | Standard Deviation 760 |
| Montelukast 5 mg CT/10-15 Year Olds | Area Under the Time-Concentration Curve (AUC 0-∞) of Montelukast CT and Montelukast OG | 3500 h*ng/mL | Standard Deviation 620 |
Primary
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Montelukast 4 mg OG/1-5 Year Olds | Maximum Plasma Concentration (Cmax) of Montelukast CT and Montelukast OG | 510 ng/mL | Standard Deviation 84 |
| Montelukast 5 mg CT/6-15 Year Olds | Maximum Plasma Concentration (Cmax) of Montelukast CT and Montelukast OG | 438 ng/mL | Standard Deviation 82 |
| Montelukast 5 mg CT/10-15 Year Olds | Maximum Plasma Concentration (Cmax) of Montelukast CT and Montelukast OG | 344 ng/mL | Standard Deviation 61 |
Primary
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Montelukast 4 mg OG/1-5 Year Olds | Percentage of Participants Who Discontinue Study Drug Due to an AE | 0.0 Percentage of participants |
| Montelukast 5 mg CT/6-15 Year Olds | Percentage of Participants Who Discontinue Study Drug Due to an AE | 2.8 Percentage of participants |
Primary
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Montelukast 4 mg OG/1-5 Year Olds | Percentage of Participants Who Experience at Least One Adverse Event (AE) | 74.5 Percentage of participants |
| Montelukast 5 mg CT/6-15 Year Olds | Percentage of Participants Who Experience at Least One Adverse Event (AE) | 55.6 Percentage of participants |
Primary
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Montelukast 4 mg OG/1-5 Year Olds | Time to Cmax (Tmax) of Montelukast CT and Montelukast OG | 2.74 Hours | Standard Deviation 0.6 |
| Montelukast 5 mg CT/6-15 Year Olds | Time to Cmax (Tmax) of Montelukast CT and Montelukast OG | 3.55 Hours | Standard Deviation 0.71 |
| Montelukast 5 mg CT/10-15 Year Olds | Time to Cmax (Tmax) of Montelukast CT and Montelukast OG | 3.65 Hours | Standard Deviation 0.6 |