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

Refractory Epilepsy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01932502
• Other study ID #: 13BN001
• Status: Active, not recruiting
• Phase: Phase 4
• First received: August 23, 2013
• Last updated: March 1, 2017
• Start date: February 2013
• Est. completion date: September 2017

Study information

• Verified date: March 2017
• Source: St. Joseph's Hospital and Medical Center, Phoenix
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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?

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 21
• Est. completion date: September 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Drug Resistant Epilepsy
• Epilepsy
• Refractory Epilepsy

Intervention

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
• 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.
• 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.
• Conversion schedule - Week 2
Week 2: Discontinuing clonazepam and increasing the dosage of Onfi by two-fold.
• Conversion schedule - Week 3
Week 3+: Titrate the dose of Onfi up to 40mg per day as tolerated.

Locations

Country	Name	City	State
United States	Banner Health	Phoenix	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
St. Joseph's Hospital and Medical Center, Phoenix	H. Lundbeck A/S

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy	Efficacy will be measured by percentage of mean seizure reduction averaged over 28 days.	28 days
Secondary	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
Secondary	Retention	Retention rate of Onfi at 6-months and 12-months.	52 weeks