Evaluation Phenobarbital as Adjunctive Therapy in Participants With Partial Onset Seizures

Phase 3

Completed

• Conditions: Epilepsy
• Interventions: Drug: Placebo tablet; Drug: Phenobarbital

• Registration Number: NCT01284556
• Lead Sponsor: West-Ward Pharmaceutical

Brief Summary

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

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

Study Timeline

• Study Start: 2010-11
• Study First Submitted: 2011-01-20
• Study First Submitted QC: 2011-01-26
• Study First Posted: 2011-01-27
• Primary Completion: 2013-01
• Study Completion: 2016-04
• Status Verified: 2017-11
• Last Update Submitted: 2017-11-09
• Last Update Posted: 2017-11-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 314

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo tablet	placebo tablets
60 mg group	Phenobarbital	Patients titrated to 60mg phenobarbital for maintenance period, then titrated down.
100 mg group	Phenobarbital	Patients titrated to 100mg phenobarbital maintenance period, then titrated down

Primary Outcome Measures

Name	Time	Method
Evaluate the efficacy of OD administration of 60 mg and 100 mg phenobarbital in reduction of seizure frequency	34 weeks with maximum 22-week exposure to phenobarbital	* 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

Secondary Outcome Measures

Name	Time	Method
Assess the effects of phenobarbital on Type I seizures	34 weeks with a maximum 22-week exposure to phenobarbital	* seizure freedom rate; * percent reduction for partial onset seizure; * responder rate; * reduction of seizure frequency
Assess the safety of phenobarbital	34 weeks with a maximum 22-week exposure to 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
Assess the tolerability of phenobarbital	34 weeks with maximum 22-week exposure to phenobarbital
Confirm the dose response relationship of 60 mg and 100 mg phenobarbital doses	34 weeks with a maximum 22-week exposure to phenobarbital

Trial Locations

Locations (4)

Centro Neurodiagnostico; 🇵🇷 Rio Piedras, Puerto Rico

Hospital Del Maestro; 🇵🇷 San Juan, Puerto Rico

Bluegrass Epilepsy Research; 🇺🇸 Lexington, Kentucky, United States

Lynn Health Science Institute; 🇺🇸 Oklahoma City, Oklahoma, United States