Safety, Tolerability, and Pharmacokinetic Study of Pregabalin in Pediatric Patients With Partial Onset Seizures

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the safety, tolerability, and pharmacokinetics of multiple doses of pregabalin in pediatric patients with partial onset seizures that are incompletely controlled on their current medications.

Official Title
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A Placebo-Controlled, Escalating Dose, Multiple Dose Study To Evaluate The Safety, Tolerability And Pharmacokinetics Of Pregabalin In Pediatric Patients With Partial Onset Seizures

Conditions
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Epilepsies, Partial

Intervention / Treatment
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* Drug: Placebo
* Drug: Pregabalin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Partial onset seizures, incompletely controlled on 1-3 medications At least 1 seizure per 28 days, on average Exclusion Criteria: Primary generalized seizures Progressive CNS pathology

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo<br>|
| Experimental: Pregabalin<br> | Drug: Pregabalin<br>* Orally-administered pregabalin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Treatment-Emergent Adverse Events (AEs) by Severity: Double-blind Treatment | Analysis for severity of AEs was performed separately for double-blind and open-label treatment. AE = any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. AEs were classified as mild, moderate and severe based on severity assessment: Mild = no interference with participant's usual function; Moderate = some interference with participant's usual function; Severe = significant interference with participant's usual function. Treatment-emergent events for double-blind treatment included events between baseline and Day 7 that were absent before treatment or that worsened relative to pretreatment state. Participants may experience more than 1 AE. | Baseline to Day 7 | 
| Number of Treatment-Emergent Adverse Events (AEs) by Severity: Open-label Treatment | Analysis for severity of AEs was performed separately for double-blind and open-label treatment. AE = any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. AEs were classified as mild, moderate and severe based on severity assessment: Mild = no interference with participant's usual function; Moderate = some interference with participant's usual function; Severe = significant interference with participant's usual function. Treatment-emergent events for open-label treatment included events between Day 8 and 28 days after the open-label dose that were absent before treatment or that worsened relative to pretreatment state. Participants may experience more than 1 AE. | Day 8 up to 28 days after open-label dose of study medication | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinically Significant Change in Physical and Neurological Findings | Full physical examination included examination of the abdomen, breasts, lungs, lymph nodes, mouth, genitourinary, musculoskeletal and neurological systems, skin, extremities, head, heart, ears, eyes, neck, nose, ocular fundi, throat and thyroid gland. The neurological exam was performed by a pediatric neurologist or qualified investigator. | Baseline up to 7 days post-last dose of study medication | 
| 28-Day Seizure Frequency Rate | Seizure frequency was reported by participant's parent or guardian from randomization to 7 days post-last dose of study medication. 28-day seizure frequency rate = (number of seizures in observation period/number of days in observation period)*28. | Baseline up to 7 days post-last dose of study medication | 
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau): Multiple-Dose Analysis | Area under the curve from time zero to the end of dosing interval (AUCtau), where dosing interval was 12 hours, for participants who received pregabalin from Day 1 to Day 8 morning is reported (multiple-dose participants). Results are normalized to individual participant's Day 8 dose. | Pre-dose, 0.5, 1, 2, 4, 8, 12 hours post-dose on Day 8 | 
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]: Single-Dose Analysis | AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). AUC (0 - ∞) for participants who received matching placebo from Day 1 to Day 7 and pregabalin on Day 8 morning is reported (single-dose participants). Results are normalized to individual participant's Day 8 dose. | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8 | 
| Maximum Observed Plasma Concentration (Cmax): Multiple-Dose Analysis | Cmax for participants who received pregabalin from Day 1 to Day 8 morning is reported (multiple-dose participants). Results are normalized to individual participant's Day 8 dose. | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8 | 
| Maximum Observed Plasma Concentration (Cmax): Single-Dose Analysis | Cmax for participants who received matching placebo from Day 1 to Day 7 and pregabalin on Day 8 morning is reported (single-dose participants). Results are normalized to individual participant's Day 8 dose. | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8 | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax): Multiple-Dose Analysis | Tmax for participants who received pregabalin from Day 1 to Day 8 morning is reported (multiple-dose participants). | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8 | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax): Single-Dose Analysis | Tmax for participants who received matching placebo from Day 1 to Day 7 and pregabalin on Day 8 morning is reported (single-dose participants). | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8 | 
| Plasma Decay Half-Life (t1/2): Multiple-Dose Analysis | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. t1/2 for participants who received pregabalin from Day 1 to Day 8 morning is reported (multiple-dose participants). | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8 | 
| Plasma Decay Half-Life (t1/2): Single-Dose Analysis | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. t1/2 for participants who received matching placebo from Day 1 to Day 7 and pregabalin on Day 8 morning is reported (single-dose participants). | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8 | 
| Apparent Oral Clearance (CL/F): Multiple-Dose Analysis | Clearance (CL) of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed (F). Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F for participants who received pregabalin from Day 1 to Day 8 morning is reported (multiple-dose participants). | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8 | 
| Apparent Oral Clearance (CL/F): Single-Dose Analysis | Clearance (CL) of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed (F). Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F for participants who received matching placebo from Day 1 to Day 7 and pregabalin on Day 8 morning is reported (single-dose participants). | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8 | 
| Renal Clearance (CLr): Multiple-Dose Analysis | Renal clearance is the volume of plasma from which the drug is completely removed by the kidney in a given amount of time. CLr for participants who received pregabalin from Day 1 to Day 8 morning is reported (multiple-dose participants). | 0 to 12 hours post-dose, 12 to 24 hours post-dose on Day 8 | 
| Renal Clearance (CLr): Single-Dose Analysis | Renal clearance is the volume of plasma from which the drug is completely removed by the kidney in a given amount of time. CLr for participants who received matching placebo from Day 1 to Day 7 and pregabalin on Day 8 morning was to be reported (single-dose participants). | 0 to 12 hours post-dose, 12 to 24 hours post-dose on Day 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Partial-onset seizures; epilepsy; pediatric; pregabalin; safety; tolerability; pharmacokinetics