A Safety, Efficacy, and Tolerability Trial of Pregabalin as Add-On Treatment in Pediatric Subjects <4 Years of Age With Partial Onset Seizures.

Study Overview
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Brief Summary
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This study is designed to evaluate the effectiveness of 2 doses of pregabalin to reduce seizure frequency as an add on therapy in pediatric subjects 1 month to <4 years of age with refractory partial onset seizures. It is hypothesized that both doses of pregabalin will demonstrate superior efficacy when compared to placebo by reducing the partial onset seizure frequency and that pregabalin will be safe and well tolerated.

Official Title
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A Double-blind, Placebo-controlled, Parallel-group, Multicenter Study Of The Efficacy And Safety Of Pregabalin As Adjunctive Therapy In Children 1 Month Through <4 Years Of Age With Partial Onset Seizures

Conditions
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Partial Onset Seizures

Intervention / Treatment
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* Drug: Pregabalin Dose Level 1
* Drug: Pregabalin Dose Level 2
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must have 3 partial onset seizures in the month prior to screening. Subject must have 2 partial onset seizures during the 48 hour baseline phase. Signed Informed Consent. On 1-3 stable anti-epileptic drugs at screening. Exclusion Criteria: Primary generalized seizures including clonic, tonic, clonic-tonic, absence, febrile seizures, and infantile spasms. Lennox-Gasteau, BECTS, and Dravet's syndrome. Status epliepticus within 1 year of screening. Any change in AED regimen with 7 days of screening. Progressive structural central nervous system (CNS) lesion or a progressive encephalopathy. Progressive errors of metabolism.

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 3 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Drug Level 1<br> | Drug: Pregabalin Dose Level 1<br>* Pregabalin liquid dosed daily three times a day in equally divided doses escalated to 7.0 mg/kg/day beginning at Randomization through Taper Phase then tapered to 3.5 mg/kg/day during 1 week Taper Phase<br>|
| Experimental: Study Drug Level 2<br> | Drug: Pregabalin Dose Level 2<br>* Pregabalin liquid dosed daily three times a day in equally divided doses escalated to 14.0 mg/kg/day beginning at Randomization through Taper Phase then tapered to 3.5 mg/kg/day during 1 week Taper Phase<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo Liquid dosed three times daily beginning at Randomization through Taper Phase<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Log Transformed 24-Hour Seizure Rate for All Partial Onset Seizures During the Double-Blind Treatment Phase | All partial onset seizures experienced during treatment phase were recorded by central reader during the 48 to 72 hour video-electroencephalogram (EEG). Double Blind 24 hour EEG seizure rate for all partial onset seizures = ([Number of seizures in double blind 48 to 72 hour EEG assessment] divided by [number of hours of video-EEG monitoring])*24. The EEG assessment was done at the end of the fixed dose treatment. For log-transformation, the quantity 1 was added to the double blind 24 hour EEG seizure rate for all participants to account for any possible 0 seizure incidence. This resulted in final calculation as: log transformed (double-blind 24-hour EEG seizure rate + 1). | Day 1 up to Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder Rate: Percentage of Participants With at Least 50 Percent (%) or Greater Reduction From Baseline in 24-Hour Seizure Rate for All Partial Onset Seizures During the Double-Blind Treatment Phase | Responder Rate was defined as percentage of participants who had a 50% or greater reduction from baseline in 24-hour seizure rate during the double-blind treatment phase. Double Blind 24 hour EEG seizure rate for all partial onset seizures = ([Number of seizures in double blind 48 to 72 hour EEG assessment] divided by [number of hours of video-EEG monitoring])*24. The EEG assessment was done at the end of the fixed dose treatment. | Day 1 up to Day 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Partial Onset Seizures, Epilepsy, Safety, Efficacy, Tolerability, Pregabalin, Lyrica, Adjunctive treatment, Placebo controlled, blinded, Eligibility Criteria