Evaluation of Onfi Conversion Therapy Replacing Clonazepam in Patients With Medically Refractory Epilepsy

Evaluation of Onfi Conversion Therapy Replacing Clonazepam in Patients With Medically Refractory Epilepsy: Efficacy, Tolerability, Dosing Equivalence, and Retention Rate

The purpose of the study is to examine the clinical safety, tolerability, and efficacy of clobazam (Onfi) when it replaces the pre-existing clonazepam therapy in patients with refractory epilepsy.

Study Overview

• Status: Unknown
• Conditions: Refractory Epilepsy
• Intervention / Treatment: Drug: clobazam (Onfi); Drug: Initial conversion and titration; Drug: Conversion schedule - Week 1; Drug: Conversion schedule - Week 2; Drug: Conversion schedule - Week 3

Detailed Description

The study is designed to answer frequently asked questions when clinicians replace existing 1,4-benzodiazepine to Onfi, as follows:

1. What should be the optimal equivalent doses for conversion?
2. How quickly should it be converted?
3. Would there be significant improvement of seizure control?
4. Should we expect difference in tolerability? If so, what are common adverse events?
5. Would the tolerance to the therapeutic effect differ with Onfi after conversion?

• Study Type: Interventional
• Enrollment (Anticipated): 21
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject has a confirmed diagnosis of medically refractory epilepsy with or without secondary generalization for at least 12 months prior to the initial study visit.
• Currently taking stable dosing regimen of clonazepam (0.5-4mg daily) for seizure control.
• Takes at least one additional Anti-epileptic drug besides benzodiazepine.
• Age 18-70 years, inclusive.
• In opinion of investigator, can be safely treated with Onfi.
• Minimum of 2 seizures, but no more than 24 complex partial or generalized seizures, during the 8-week baseline period prior to study entry.
• Able to communicate effectively with study personnel and considered reliable, able, willing, and cooperative with regard to complying with protocol-defined requirements, including completion of study diary.

Exclusion Criteria:

• Clinically relevant current illness or history of that may interfere with the subject's ability to complete the study as determined by the investigator.
• History of status epilepticus within 6 months prior to the initial study visit.
• History of suicidal attempts or suicidal ideation within 12 months of initial visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: clonazepam conversion to clobazam (Onfi); Subject's clonazepam will be converted to clobazam (Onfi). This is an open label study without placebo control.

Drug: clobazam (Onfi); Subject's clonazepam will be converted to the following Onfi doses per day: Clonazepam 0.5mg converted to Onfi 10mg first week, then titrated up to 40mg per day. Clonazepam 1.0-2.0mg converted to Onfi 20mg first week, then titrated up to 40mg per day. Clonazepam 2-4mg converted to Onfi 20mg first week, then titrated up to 60mg per day. Initial conversion will occur over two weeks followed by upward titration of up to 10mg increment per week toward the target dose. Down titration of up to 10mg will be allowed during the study. The following will be the initial conversion schedule from clonazepam to Onfi: Week 1: 50% reduction of clonazepam and starting dose of Onfi, replacing the reduced clonazepam dose with the conversion rate of clonazepam 0.5mg = Onfi 10mg. Week 2: Discontinuing clonazepam and increasing the dosage of Onfi by two-fold. Week 3+: Titrate the dose of Onfi up to 40mg per day as tolerated; Drug: Initial conversion and titration; Initial conversion will occur over two weeks followed by upward titration of up to 10mg increment per week toward the target dose. Down titration of up to 10mg will be allowed during the study.; Other Names: clobazam (Onfi); Drug: Conversion schedule - Week 1; The following will be the initial conversion schedule from clonazepam to Onfi: Week 1: 50% reduction of clonazepam and starting dose of Onfi, replacing the reduced clonazepam dose with the conversion rate of clonazepam 0.5mg=Onfi 10mg.; Other Names: clobazam (Onfi); Drug: Conversion schedule - Week 2; Week 2: Discontinuing clonazepam and increasing the dosage of Onfi by two-fold.; Other Names: clobazam (Onfi); Drug: Conversion schedule - Week 3; Week 3+: Titrate the dose of Onfi up to 40mg per day as tolerated.; Other Names: clobazam (Onfi)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy	Efficacy will be measured by percentage of mean seizure reduction averaged over 28 days.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability	Retention rate, which indirectly measures the therapeutic tolerance, will be measured at 6 weeks, 12 weeks, 24 weeks, and 52 weeks.	Weeks 6 - 52 after medication conversion
Retention	Retention rate of Onfi at 6-months and 12-months.	52 weeks

Collaborators and Investigators

• Sponsor: St. Joseph's Hospital and Medical Center, Phoenix
• Collaborators: H. Lundbeck A/S
• Investigators: Principal Investigator: Steve Chung, MD, Banner Health Systems

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Anticipated): June 1, 2017
• Study Completion (Anticipated): September 1, 2017

Study Registration Dates

• First Submitted: August 23, 2013
• First Submitted That Met QC Criteria: August 27, 2013
• First Posted (Estimate): August 30, 2013

Study Record Updates

• Last Update Posted (Actual): March 3, 2017
• Last Update Submitted That Met QC Criteria: March 1, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: epilepsy; Onfi; clonazepam
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Drug Resistant Epilepsy; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Anti-Anxiety Agents; GABA Agents; Anticonvulsants; GABA-A Receptor Agonists; GABA Agonists; Clobazam
• Other Study ID Numbers: 13BN001