A Safety, Efficacy and Tolerability Trial of Pregabalin as Add-On Treatment in Pediatric and Adult Subjects With Primary Generalized Tonic-Clonic (i.e., Grand Mal) Seizures.

Study Overview
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Brief Summary
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The study is designed to evaluate the safety, tolerability and efficacy of two doses of pregabalin as add-on treatment in pediatric and adult subjects with Primary Generalized Tonic-Clonic (PGTC) seizures as compared to placebo. It is hypothesized that both doses of pregabalin will demonstrated superior efficacy when compared to placebo by reducing PGTC seizure frequency and that pregabalin will be safe and well tolerated.

Official Title
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A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL GROUP, MULTI-CENTER TRIAL OF PREGABALIN AS ADJUNCTIVE THERAPY IN PEDIATRIC AND ADULT SUBJECTS WITH PRIMARY GENERALIZED TONIC-CLONIC SEIZURES - PROTOCOL A0081105

Conditions
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Generalized Tonic Clonic 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: Seizures classified as Primary Generalized Tonic Clonic Seizures Must have at least 1 PGTC seizure in the 8 weeks prior to screening Must have a minimum of 3 PGTC seizures during the 8-week baseline phase and at least 1 PGTC in each 4-week period of the baseline phase Currently receiving adequate and stable dosage of 1 to 3 anti-epileptic treatments (stable within 28 days of screening) Signed informed consent and assent if a minor Ability to comply with daily seizure and dosing diary requirements and all study procedures Exclusion Criteria: A current diagnosis of febrile seizures, or seizures related to an ongoing acute medical illness Focal seizures (simple partial, complex partial, or partial becoming secondarily generalized) Status Epilepticus within 1 year prior to screening Lennox-Gastaut syndrome, infantile spasms, Benign Epilepsy with Centrotemporal Spikes (BECTS) and Dravet syndrome Seizures related to drugs, alcohol, or acute medical illness Any change in anti-epileptic treatment regimen (type of medication or dose; VNS alteration) within 28 days of the screening visit or during the baseline phase Progressive or potentially progressive structural CNS lesion or a progressive encephalopathy. Progressive inborn errors of metabolism.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 65 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, either liquid or capsule, dosed twice daily, escalated up to a maximum of 300 mg/day beginning at Randomization to Taper Phase, then tapered down to a maximum dose of 150 mg/day during 1 week Taper Phase to End of Study/Early Termination.<br>* Other names: Lyrica Dose Level 1;|
| Experimental: Study Drug Level 2<br> | Drug: Pregabalin Dose Level 2<br>* Pregabalin, either liquid or capsule, dosed twice daily, escalated up to a maximum of 600 mg/day beginning at Randomization to Taper Phase, then tapered down to a maximum of 150 mg/day during 1 week Taper Phase to End of Study/Early Termination.<br>* Other names: Lyrica Dose Level 2;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo, either liquid or capsule, dosed twice daily beginning at Randomization to End of Study/Early Termination.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Log-transformed (Log) 28-day Seizure Rate for All Primary Generalized Tonic-Clonic (PGTC) Seizures During 12-Week Double-Blind Treatment Phase | All PGTC seizures experienced during treatment phase were recorded by the participants or their parents/legal guardian in a daily seizure diary. 28-day seizure rate for all PGTC seizures= ([number of seizures in the double blind treatment phase] divided by [number of days in double blind treatment phase minus {-} number of missing diary days in treatment phase])*28. For log-transformation, the quantity 1 was added to the 28-day seizure rate for all participants to account for any possible 0 seizure incidence. This resulted in final calculation as: log transformed (28-day seizure rate +1). | Day 1 up to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With at Least 50 Percent (%) or Greater Reduction From Baseline in 28-day Primary Generalized Tonic-clonic (PGTC) Seizure Rate During the 12-Week Double-blind Treatment Phase | Percentage of participants with 50% or greater reduction from baseline in 28-day seizure rate during the 12 week double blind treatment phase were reported. 28-day seizure rate for all PGTC seizures= ([number of seizures in the double blind treatment phase] divided by [number of days in double blind treatment phase minus {-} number of missing diary days in treatment phase])*28. | Day 1 up to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary Generalized Tonic Clonic Seizures, Epilepsy, Safety, Efficacy, Tolerability, Pregabalin, Lyrica, Adjunctive treatment, Placebo Controlled, Blinded