Evaluation Phenobarbital as Adjunctive Therapy in Participants With Partial Onset Seizures

Study Overview
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Brief Summary
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Primary: - to evaluate the efficacy of phenobarbital in reducing seizure frequency. Secondary: to confirm dose response relationship, to assess the effects on Type I seizures, to assess the safety of phenobarbital to assess the drug tolerability.

Detailed Description
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Primary: -to evaluate the efficacy of once daily (OD) administration of 60 mg and 100 mg phenobarbital, in reducing seizure frequency in participants with partial onset seizures (Type I seizures; complex or simple with motor symptoms only) not fully controlled despite treatment with 1 to 3 concomitant anti-epileptic drugs (AEDs) or AEDs with Vagus Nerve Stimulator (VNS) Secondary: to confirm dose response relationship of 60 and 100 mg phenobarbital doses, to assess the effects of phenobarbital on Type I seizures, to assess the safety of phenobarbital to assess the tolerability of phenobarbital

Official Title
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An International, Double-blind, Parallel-group, Placebo-controlled, Randomized Study: Evaluation of the Efficacy and Safety of Phenobarbital as Adjunctive Therapy in Participants (> or = 17 to 70 Years Old) With Partial Onset Seizures

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: Phenobarbital
* Drug: Placebo tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: participants from 17 to 70 years old; history of Type I partial onset seizures (complex or simple with motor symptoms only); participants must have had electroencephalogram (EEG), magnetic resonance imaging (MRI) or computed tomography (CT) with results consistent with diagnosis of partial-onset seizures; participants having at least eight Type I partial onset seizures during 8-week baseline period; participants being uncontrolled while treated by 1 to 3 permitted concomitant anti-epileptic drug (AED) and/or Vagus Nerve Stimulation (VNS); participant has been on a stable dose of their current anti-epileptic treatment regime Exclusion Criteria: currently taking phenobarbital or primidone; currently taking felbamate or vigabatrin; history of prior allergic reaction to phenobarbital; history of psychogenic seizures; history or presence of status epilepticus; history or presence of seizures occurring only in clusters; participant taking any drug with possible Central Nervous System (CNS) effects except if stable from 1 month prior Visit 1; history of cerebrovascular accident (CVA) or transient ischemic attack (TIA); presence of any sign suggesting rapidly progressing brain disorder or brain tumor; presence of unstable arteriovenous malformations, meningiomas or other benign tumors; history of porphyria; presence of clinically significant findings on physical exam, vital signs, electrocardiogram (ECG) or safety lab assessments, including renal or hepatic insufficiency; history of alcohol or drug abuse within the year prior to screening; participant who is known to be non-compliant; participant who is male or female who refuses to use an acceptable form of contraception; female who is pregnant or lactating or intends to become pregnant; participant who has taken part in any investigational device or product within 2 months prior to the screening visit

Ages Eligible for Study
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Minimum Age: 17 Years
Maximum Age: 70 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>placebo tablets | Drug: Placebo tablet<br>* tablet<br>|
| Experimental: 60 mg group<br>Patients titrated to 60mg phenobarbital for maintenance period, then titrated down. | Drug: Phenobarbital<br>* tablet<br>|
| Experimental: 100 mg group<br>Patients titrated to 100mg phenobarbital maintenance period, then titrated down | Drug: Phenobarbital<br>* tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the efficacy of OD administration of 60 mg and 100 mg phenobarbital in reduction of seizure frequency | determination of partial onset seizure frequency per week over the treatment period comparison of average change in weekly seizure rate from baseline and maintenance period | 34 weeks with maximum 22-week exposure to phenobarbital | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirm the dose response relationship of 60 mg and 100 mg phenobarbital doses |  | 34 weeks with a maximum 22-week exposure to phenobarbital | 
| Assess the effects of phenobarbital on Type I seizures | seizure freedom rate percent reduction for partial onset seizure responder rate reduction of seizure frequency | 34 weeks with a maximum 22-week exposure to phenobarbital | 
| Assess the safety of phenobarbital | overview of adverse events in study summary of adverse events in study by severity, seriousness, relationship to study drug, action taken, outcome, treatment summary of serious adverse events | 34 weeks with a maximum 22-week exposure to phenobarbital | 
| Assess the tolerability of phenobarbital |  | 34 weeks with maximum 22-week exposure to phenobarbital | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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partial onset seizures