Evaluation Phenobarbital as Adjunctive Therapy in Participants With Partial Onset Seizures

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

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.

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Drug: Placebo tablet; Drug: Phenobarbital

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 Type: Interventional
• Enrollment (Actual): 314
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • Rio Piedras, Puerto Rico, 00924
    • Centro Neurodiagnostico
  • San Juan, Puerto Rico, 00927
    • Hospital Del Maestro
• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • Bluegrass Epilepsy Research
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 70 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; placebo tablets	Drug: Placebo tablet; tablet
EXPERIMENTAL: 60 mg group; Patients titrated to 60mg phenobarbital for maintenance period, then titrated down.	Drug: Phenobarbital; tablet
EXPERIMENTAL: 100 mg group; Patients titrated to 100mg phenobarbital maintenance period, then titrated down	Drug: Phenobarbital; tablet

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: West-Ward Pharmaceutical

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (ACTUAL): January 1, 2013
• Study Completion (ACTUAL): April 1, 2016

Study Registration Dates

• First Submitted: January 20, 2011
• First Submitted That Met QC Criteria: January 26, 2011
• First Posted (ESTIMATE): January 27, 2011

Study Record Updates

• Last Update Posted (ACTUAL): November 14, 2017
• Last Update Submitted That Met QC Criteria: November 9, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: partial onset seizures
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Seizures; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Hypnotics and Sedatives; GABA Modulators; GABA Agents; Anticonvulsants; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP2B6 Inducers; Phenobarbital
• Other Study ID Numbers: AGG-901; 2010-020871-22 (EUDRACT_NUMBER)