Clinical trial NCT00849212: An add-on Study of E2007 in Patients With Refractory Partial Seizures Uncontrolled With Other Anti-epileptic Drugs (AEDs)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Refractory Partial Seizures
Keywords: Seizures
epilepsy
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2009-02-23
Enrollment: 30
Sex: ALL
Minimum age (years): 20
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: 10 weeks (Titration and Maintenance Periods)
Secondary outcomes:
measure: Percent Change in Total Seizure Frequency Per 28 Days From Baseline (Maintenance Period) ; LOCF
timeFrame: Baseline (Day -28 to Day 0), Week 1 to Week 10
Other outcomes:
Locations:
city: Kitakyushu
country: Japan
state: Fukuoka
city: Kobe
country: Japan
state: Hyogo
city: Sendai
country: Japan
state: Miyagi
city: Komatsushima
country: Japan
state: Tokushima
city: Kodaira
country: Japan
state: Tokyo
city: Kyoto
country: Japan
city: Nagasaki
country: Japan
city: Niigata
country: Japan
city: Shizuoka
country: Japan
Study officials:
affiliation: New Drug Development Department, Eisai Company Limited
name: Hidetaka Hiramatsu
role: STUDY_DIRECTOR
References:
citation: Maguire M. Response to "Perampanel and pregnancy: Could experience be a gloomy lantern that does not even illuminate its bearer?". Epilepsy Behav. 2022 Apr;129:108654. doi: 10.1016/j.yebeh.2022.108654. Epub 2022 Mar 16. No abstract available.