Evaluation Phenobarbital as Adjunctive Therapy in Participants With Partial Onset Seizures

• ClinicalTrials.gov Identifier: NCT01284556
• Recruitment Status: Completed
• First Posted: January 27, 2011
• Last Update Posted: November 14, 2017
• Sponsor: West-Ward Pharmaceutical
• Information provided by (Responsible Party): West-Ward Pharmaceutical

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Epilepsy	Drug: Phenobarbital; Drug: Placebo tablet	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 314 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: November 2010
• Actual Primary Completion Date: January 2013
• Actual Study Completion Date: April 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Evaluate the efficacy of OD administration of 60 mg and 100 mg phenobarbital in reduction of seizure frequency [ Time Frame: 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 :

1. Confirm the dose response relationship of 60 mg and 100 mg phenobarbital doses [ Time Frame: 34 weeks with a maximum 22-week exposure to phenobarbital ]
2. Assess the effects of phenobarbital on Type I seizures [ Time Frame: 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
3. Assess the safety of phenobarbital [ Time Frame: 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
4. Assess the tolerability of phenobarbital [ Time Frame: 34 weeks with maximum 22-week exposure to phenobarbital ]

Eligibility Criteria

• Ages Eligible for Study: 17 Years to 70 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Kentucky

Bluegrass Epilepsy Research

Lexington, Kentucky, United States, 40504

United States, Oklahoma

Lynn Health Science Institute

Oklahoma City, Oklahoma, United States, 73112

Puerto Rico

Centro Neurodiagnostico

Rio Piedras, Puerto Rico, 00924

Hospital Del Maestro

San Juan, Puerto Rico, 00927

Sponsors and Collaborators

West-Ward Pharmaceutical

More Information

• Responsible Party: West-Ward Pharmaceutical
• ClinicalTrials.gov Identifier: NCT01284556
• Other Study ID Numbers: AGG-901; 2010-020871-22 ( EudraCT Number )
• First Posted: January 27, 2011
• Last Update Posted: November 14, 2017
• Last Verified: November 2017

Keywords provided by West-Ward Pharmaceutical:

partial onset seizures

Additional relevant MeSH terms:

Seizures; Nervous System Diseases; Neurologic Manifestations; Phenobarbital; Anticonvulsants; Hypnotics and Sedatives; Central Nervous System Depressants; Physiological Effects of Drugs; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; GABA Modulators; GABA Agents; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers