Perennial Allergic Rhinitis
Conditions
Brief summary
This is a post marketing study to confirm the appropriate dose of loratadine in children by obtaining drug concentration data at multiple time points per child and adult patient, after the patient receives repeated administrations of the approved dose of loratadine.
Interventions
DRUGloratadine
Loratadine (SCH 29851) dry syrup 1% 5 mg/day for 4 weeks
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
Patients with perennial allergic rhinitis who satisfy all of the following criteria were enrolled in the study: * Pediatric patients between the ages of 3 and 15 years and adult patients between the ages of 16 and 64 at the time of providing informed consent. * Outpatients of either sex. * Pediatric patients for whom written informed consent can be obtained from the guardian before the start of the study. Adult patients from whom written informed consent can be obtained (for patients between the ages of 16 and 19, the guardian must also provide written informed consent). * Pediatric patients who have the ability to make entries in the patient diary (Record of Drugs and Nasal Symptoms) or entry in the diary is made possible by the guardian. Adult patients who have the ability to make entries in the patient diary. * Patients for whom treatment with loratadine monotherapy is judged appropriate based on symptoms of allergic rhinitis during the pretreatment observation period. * Patients confirmed to be allergic to perennial allergen
Exclusion criteria
* Patients with a history of epileptic seizures or organic brain disorder in whom there is a possibility that epileptic seizures may be induced * Patients with a history of hypersensitivity to any component of this drug * Patients who are pregnant or who may be pregnant, and nursing women * Patients with severe hepatic, renal, cardiac, or hematological disease or other serious complications and whose general condition is poor * Patients participating in another clinical study or who have been in a clinical study within the last 30 days. * Other patients judged inappropriate for study by the investigator or sub-investigator * Patients allergic to pollen (cedar, mugwort, common ragweed, orchard grass, etc.) and the pollen season is during the period from 7 days before registration to the end of study drug administration * Patients who developed diseases which might affect nasal symptoms (acute upper respiratory tract infection, acute pharyngo-laryngitis, or acute tonsillitis) in the 7 days before registration * Patients who received treatment for allergic rhinitis in the 7 days before registration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Maximum Plasma Concentration (Cmax) of SCH 29851 (Unchanged Drug; Loratadine), SCH 34117 (Active Metabolite), and SCH 45581 (3OH-SCH 34117) | After 2 and 4 weeks of treatment, and after 1 and 3 weeks of treatment if participant agreed | SCH 29851: Two-compartment model used as basic pharmacokinetic (PK) model. Individual Cmax estimated with basic PPK parameters (apparent total body clearance (CL/F), apparent distribution volumes of central compartment (Vc/F) and peripheral compartment (Vp/F), apparent inter-compartmental clearance (Q/F), absorption rate constant (Ka), lag time, inter- and intra-individual variation) by Bayesian method. SCH 34117/SCH 45581: One-compartment model used as basic PK model. Individual Cmax was estimated with PPK parameters (above) on final model by Bayesian method. |
| Mean Area Under the Plasma Concentration Time Curve (AUC) of SCH 29851 (Unchanged Drug), SCH 34117 (Active Metabolite), and SCH 45581 (3OH-SCH 34117) | After 2 and 4 weeks of treatment, and after 1 and 3 weeks of treatment if participant agreed | SCH 29851: Two-compartment model used as basic pharmacokinetic (PK) model. Individual AUC estimated with basic PPK parameters (apparent total body clearance (CL/F), apparent distribution volumes of central compartment (Vc/F) and peripheral compartment (Vp/F), apparent inter-compartmental clearance (Q/F), absorption rate constant (Ka), lag time, inter- and intra-individual variation) by Bayesian method. SCH 34117/SCH 45581: One-compartment model used as basic PK model. Individual AUC was estimated with PPK parameters (above) on final model by Bayesian method. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pediatrics 3 to 6 Years Pediatrics 3 to 6 years of age received loratadine 5 mg/day for 28 days | 53 |
| Pediatrics 7 to 15 Years Pediatrics 7 to 15 years of age received loratadine 10 mg/day for 28 days | 104 |
| Adults 16 to 64 Years Adults 16 to 64 years of age received loratadine 10 mg/day for 28 days | 104 |
| Total | 261 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Discontinued | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Adults 16 to 64 Years | Pediatrics 7 to 15 Years | Pediatrics 3 to 6 Years |
|---|---|---|---|---|
| Age, Customized Between 16 - 64 years | 104 participants | 104 participants | 0 participants | 0 participants |
| Age, Customized Between 3-6 years | 53 participants | 0 participants | 0 participants | 53 participants |
| Age, Customized Between 7 and 15 years | 104 participants | 0 participants | 104 participants | 0 participants |
| Sex: Female, Male Female | 113 Participants | 68 Participants | 29 Participants | 16 Participants |
| Sex: Female, Male Male | 148 Participants | 36 Participants | 75 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 23 / 53 | 17 / 104 | 17 / 104 |
| serious Total, serious adverse events | 0 / 53 | 0 / 104 | 0 / 104 |
Outcome results
Primary
Mean Area Under the Plasma Concentration Time Curve (AUC) of SCH 29851 (Unchanged Drug), SCH 34117 (Active Metabolite), and SCH 45581 (3OH-SCH 34117)
SCH 29851: Two-compartment model used as basic pharmacokinetic (PK) model. Individual AUC estimated with basic PPK parameters (apparent total body clearance (CL/F), apparent distribution volumes of central compartment (Vc/F) and peripheral compartment (Vp/F), apparent inter-compartmental clearance (Q/F), absorption rate constant (Ka), lag time, inter- and intra-individual variation) by Bayesian method. SCH 34117/SCH 45581: One-compartment model used as basic PK model. Individual AUC was estimated with PPK parameters (above) on final model by Bayesian method.
Time frame: After 2 and 4 weeks of treatment, and after 1 and 3 weeks of treatment if participant agreed
Population: Number of participants for SCH 29851 were 53, 104, and 104. Number of participants for SCH 34117 were 53, 102, and 104. Number of participants for SCH 44581 were 53, 99, and 104.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pediatrics 3 to 6 Years | Mean Area Under the Plasma Concentration Time Curve (AUC) of SCH 29851 (Unchanged Drug), SCH 34117 (Active Metabolite), and SCH 45581 (3OH-SCH 34117) | SCH 34117 | 52.33 ng•hr/mL | Standard Deviation 15.63 |
| Pediatrics 3 to 6 Years | Mean Area Under the Plasma Concentration Time Curve (AUC) of SCH 29851 (Unchanged Drug), SCH 34117 (Active Metabolite), and SCH 45581 (3OH-SCH 34117) | SCH 29851 | 16.77 ng•hr/mL | Standard Deviation 14.87 |
| Pediatrics 3 to 6 Years | Mean Area Under the Plasma Concentration Time Curve (AUC) of SCH 29851 (Unchanged Drug), SCH 34117 (Active Metabolite), and SCH 45581 (3OH-SCH 34117) | SCH 45581 | 41.54 ng•hr/mL | Standard Deviation 11.43 |
| Pediatrics 7 to 15 Years | Mean Area Under the Plasma Concentration Time Curve (AUC) of SCH 29851 (Unchanged Drug), SCH 34117 (Active Metabolite), and SCH 45581 (3OH-SCH 34117) | SCH 34117 | 59.52 ng•hr/mL | Standard Deviation 23.73 |
| Pediatrics 7 to 15 Years | Mean Area Under the Plasma Concentration Time Curve (AUC) of SCH 29851 (Unchanged Drug), SCH 34117 (Active Metabolite), and SCH 45581 (3OH-SCH 34117) | SCH 29851 | 26.13 ng•hr/mL | Standard Deviation 22.22 |
| Pediatrics 7 to 15 Years | Mean Area Under the Plasma Concentration Time Curve (AUC) of SCH 29851 (Unchanged Drug), SCH 34117 (Active Metabolite), and SCH 45581 (3OH-SCH 34117) | SCH 45581 | 42.28 ng•hr/mL | Standard Deviation 14.4 |
| Adults 16 to 64 Years | Mean Area Under the Plasma Concentration Time Curve (AUC) of SCH 29851 (Unchanged Drug), SCH 34117 (Active Metabolite), and SCH 45581 (3OH-SCH 34117) | SCH 29851 | 34.68 ng•hr/mL | Standard Deviation 37.22 |
| Adults 16 to 64 Years | Mean Area Under the Plasma Concentration Time Curve (AUC) of SCH 29851 (Unchanged Drug), SCH 34117 (Active Metabolite), and SCH 45581 (3OH-SCH 34117) | SCH 45581 | 40.75 ng•hr/mL | Standard Deviation 9.92 |
| Adults 16 to 64 Years | Mean Area Under the Plasma Concentration Time Curve (AUC) of SCH 29851 (Unchanged Drug), SCH 34117 (Active Metabolite), and SCH 45581 (3OH-SCH 34117) | SCH 34117 | 68.01 ng•hr/mL | Standard Deviation 23.33 |
Primary
Mean Maximum Plasma Concentration (Cmax) of SCH 29851 (Unchanged Drug; Loratadine), SCH 34117 (Active Metabolite), and SCH 45581 (3OH-SCH 34117)
SCH 29851: Two-compartment model used as basic pharmacokinetic (PK) model. Individual Cmax estimated with basic PPK parameters (apparent total body clearance (CL/F), apparent distribution volumes of central compartment (Vc/F) and peripheral compartment (Vp/F), apparent inter-compartmental clearance (Q/F), absorption rate constant (Ka), lag time, inter- and intra-individual variation) by Bayesian method. SCH 34117/SCH 45581: One-compartment model used as basic PK model. Individual Cmax was estimated with PPK parameters (above) on final model by Bayesian method.
Time frame: After 2 and 4 weeks of treatment, and after 1 and 3 weeks of treatment if participant agreed
Population: Number of participants for SCH 29851 were 53, 104, and 104. Number of participants for SCH 34117 were 53, 102, and 104. Number of participants for SCH 44581 were 53, 99, and 104.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pediatrics 3 to 6 Years | Mean Maximum Plasma Concentration (Cmax) of SCH 29851 (Unchanged Drug; Loratadine), SCH 34117 (Active Metabolite), and SCH 45581 (3OH-SCH 34117) | SCH 34117 | 4.16 ng/mL | Standard Deviation 1.26 |
| Pediatrics 3 to 6 Years | Mean Maximum Plasma Concentration (Cmax) of SCH 29851 (Unchanged Drug; Loratadine), SCH 34117 (Active Metabolite), and SCH 45581 (3OH-SCH 34117) | SCH 29851 | 3.04 ng/mL | Standard Deviation 1.78 |
| Pediatrics 3 to 6 Years | Mean Maximum Plasma Concentration (Cmax) of SCH 29851 (Unchanged Drug; Loratadine), SCH 34117 (Active Metabolite), and SCH 45581 (3OH-SCH 34117) | SCH 45581 | 2.58 ng/mL | Standard Deviation 0.76 |
| Pediatrics 7 to 15 Years | Mean Maximum Plasma Concentration (Cmax) of SCH 29851 (Unchanged Drug; Loratadine), SCH 34117 (Active Metabolite), and SCH 45581 (3OH-SCH 34117) | SCH 34117 | 4.30 ng/mL | Standard Deviation 1.63 |
| Pediatrics 7 to 15 Years | Mean Maximum Plasma Concentration (Cmax) of SCH 29851 (Unchanged Drug; Loratadine), SCH 34117 (Active Metabolite), and SCH 45581 (3OH-SCH 34117) | SCH 29851 | 5.54 ng/mL | Standard Deviation 3.15 |
| Pediatrics 7 to 15 Years | Mean Maximum Plasma Concentration (Cmax) of SCH 29851 (Unchanged Drug; Loratadine), SCH 34117 (Active Metabolite), and SCH 45581 (3OH-SCH 34117) | SCH 45581 | 2.56 ng/mL | Standard Deviation 0.86 |
| Adults 16 to 64 Years | Mean Maximum Plasma Concentration (Cmax) of SCH 29851 (Unchanged Drug; Loratadine), SCH 34117 (Active Metabolite), and SCH 45581 (3OH-SCH 34117) | SCH 29851 | 6.48 ng/mL | Standard Deviation 3.28 |
| Adults 16 to 64 Years | Mean Maximum Plasma Concentration (Cmax) of SCH 29851 (Unchanged Drug; Loratadine), SCH 34117 (Active Metabolite), and SCH 45581 (3OH-SCH 34117) | SCH 45581 | 2.35 ng/mL | Standard Deviation 0.54 |
| Adults 16 to 64 Years | Mean Maximum Plasma Concentration (Cmax) of SCH 29851 (Unchanged Drug; Loratadine), SCH 34117 (Active Metabolite), and SCH 45581 (3OH-SCH 34117) | SCH 34117 | 4.61 ng/mL | Standard Deviation 1.41 |