An add-on Study of E2007 in Patients With Refractory Partial Seizures Uncontrolled With Other Anti-epileptic Drugs (AEDs)

Refractory Partial Seizures Clinical Trial

Official title:

A Phase II, Open-label, Ascending High-dose, add-on Study of E2007 in Patients With Refractory Partial Seizures Uncontrolled With Other Anti-epileptic Drugs (AEDs)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00849212
• Other study ID #: E2007-J081-231
• Status: Completed
• Phase: Phase 2
• First received: February 20, 2009
• Last updated: January 3, 2013
• Start date: April 2009
• Est. completion date: November 2009

Study information

• Verified date: January 2013
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to explore the maximum tolerated dose of E2007 in Japanese patients with refractory partial seizures which are uncontrolled with other anti-epileptic drugs (AEDs). Thirty patients will receive E2007 (dose escalating to the maximum of 12 mg per day). The dose of E2007 will be adjusted during 6 weeks. Subsequently, the dose will be fixed and maintained during 4 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: November 2009
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 64 Years

Eligibility

Inclusion criteria:

1. Male or female aged between 20 and 64 years old.

2. Patients diagnosed with partial seizure (including secondarily generalized seizure).

3. Patients who have at least 3 counts of partial seizures during the previous 4 weeks prior to observation start and no seizure-free for 21 days during 8 weeks before the treatment start based on medical records. Simple partial seizure without motor signs will not be counted.

4. Patients who have been treated for at least 12 weeks but confirmed to be uncontrolled with more than one standard AED for 2 years.

5. Patients treated with stable doses of up to three AEDs. Only one cytochrome

P450 (CYP) 3A4 inducer shown below will be allowed for concomitant use:

• Carbamazepine

• Phenytoin

• Phenobarbital

• Primidone

6. Patients on stable dose of anti-depressants, anti-anxiety drugs, or mood stabilizers from before 8 weeks.

Exclusion criteria:

1. Patients with present or a history of Lennox-Gastaut syndrome.

2. Patients with present generalized seizures (e.g., absence, myoclonic).

3. Patients with a history of status epilepticus within 1 year.

4. Patients with seizure clusters where individual seizure cannot be counted within 8 weeks.

5. Patients with a history of psychogenic seizure.

6. Patients who underwent surgical operation for epilepsy within 2 years.

7. Patients using rescue benzodiazepines at least twice in a 4-week duration within 8 weeks (if 1 or 2 doses over 24-hour period considered one-time rescue).

8. Patients whose alanine aminotransferase (ALT) or aspartate aminotransferase (AST) at enrollment in observation period exceeds 1.5-fold the upper limit of normal (ULN), but those whose ALT or AST are constantly higher than ULN, they can enroll if ALT or AST remain in 3-fold the ULN.

9. Patients with significant active hematological disease; white blood cell (WBC) count </=2500/uL or neutrophil count </=1000 uL.

10. Patients on anti-psychotics or who have psychotic disorder and/or psychotic disorder(s) or unstable recurrent affective disorder(s) with a history of suicidal attempt within 2 years.

11. Patients who operate heavy equipment or drive should not be recruited into the study.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Refractory Partial Seizures
• Seizures

Intervention

Drug:
• E2007
The dose of E2007 will start from 2 mg and will be increased by 2 mg every week up to 12 mg (the maximum dose). The dose will be adjusted during 6 weeks (i.e., titration period). Subsequently, the dose will be fixed and maintained during 4 weeks (Maintenance period). Patients must visit study site at Weeks -4, 1, 2, 3, 4, 5, 6, 8, 10 and 14 to confirm.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Co., Ltd.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD)	MTD was defined by participants. For participants who completed treatment, MTD was dose at last administration. For subjects who discontinued due to adverse event (AE), the MTD depended on the number of days within down-titration. If these criteria were not applied, the MTD was determined based on suggestions from the Tolerability and Safety Evaluation Committee.	10 weeks (Titration and Maintenance Periods)	No
Secondary	Percent Change in Total Seizure Frequency Per 28 Days From Baseline (Maintenance Period) ; LOCF	The percent change in seizure frequency per 28 days during the maintenance period was collected via patient diary cards. This was calculated using the last observation carried forward (LOCF) method.	Baseline (Day -28 to Day 0), Week 1 to Week 10	No