Clinical trial NCT03780907: Safety and Pharmacokinetics Study of E2007 to Treat Partial and Generalised Seizures in People With Epilepsy
Official title: A Randomised, Double-Blind, Placebo-Controlled Study of the Tolerability, Safety and Pharmacokinetics of E2007 in Epileptic Patients With Partial and Generalised Seizures
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Epilepsy
Keywords: Epilepsy
E2007
partial seizures
generalized seizures
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2018-12-19
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objectives of this study were to assess the tolerability and safety of E2007 in patients with refractory partial or generalised seizures and to assess the pharmacokinetics of E2007 in epileptic patients receiving at least one concomitant anti-epileptic drug.


Eligibility criteria: Inclusion Criteria

A patient who met the following inclusion criteria was eligible to participate in the study:

1. Males or females with simple or complex partial seizures with or without secondary generalization, or primary generalized tonic-clonic seizures according to the International League against Epilepsy classification. Patient records were to document the frequency of seizure.
2. Age: 18 to 65 years.
3. Race: any.
4. Patients receiving up to two additional anti-epileptic medications at doses that were stable for at least the four weeks immediately preceding baseline.
5. Patients willing and able to co-operate with the study procedures including completion of patient diaries.
6. Patients living at home with a partner or carer able to monitor compliance.
7. Patients giving informed consent to participate in the study.

Exclusion Criteria

A patient who met the following exclusion criteria was not eligible to participate in the study:

1. Pregnant or lactating women.
2. Women of childbearing potential unless (1) surgically sterile or (2) practicing effective contraception (eg, abstinence, IUD or barrier method plus hormonal method) and having a negative serum beta-HCG result at screening and being willing to remain on the current form of contraception for the duration of the study. Postmenopausal women could be included but were to have been amenorrhoeic for at least 12 months to be considered as not being of child-bearing potential.
3. Fertile men not willing to use reliable contraception or with partners not willing to use reliable contraception.
4. Patients with status epilepticus within the past 24 months.
5. Patients with unstable abnormalities of the hepatic, renal, cardiovascular, respiratory, abdominal, haematological, endocrine or metabolic systems which might complicate assessment of the tolerability of the study medication.
6. Patients with significantly elevated liver enzymes (abnormal bilirubin level, or serum transaminase levels more than 1.5 times the upper limit of normal).
7. Patients taking drugs other than anti-epileptic agents which induce the enzyme cytochrome P450 3A4 (since these might reduce the plasma concentration of E2007), including dexamethasone, rifabutin, rifampacin, St John's Wort.
8. Patients with past or present drug or alcohol abuse.
9. Patients with unstable psychiatric illness.
10. Patients who had received an investigational drug within the three months before baseline.
11. Patients without a reliable partner or carer.
12. Patients with any condition which would make the patient, in the opinion of the investigator, unsuitable for the study.

Primary outcomes:
measure: Number of participants with Treatment Emergent Adverse Events (TEAEs)
timeFrame: From administration of first dose of study drug up until 42 days.
measure: Clinical Global Impression of Tolerability (CGIT)
timeFrame: Day 28
measure: Pharmacokinetic Parameter: Area Under the Curve (AUC)(0-24hr) of E2007
timeFrame: Day 1 and Day 14
measure: Pharmacokinetic Parameter: Cmax (Maximum Observed Plasma Concentration) of E2007
timeFrame: Day 1 and Day 14
measure: Pharmacokinetic Parameter: Tmax (Time to Maximum Concentration) of E2007
timeFrame: Day 1 and Day 14
measure: Pharmacokinetic Parameter: Css,min (Minimum Steady State Plasma Concentration) of E2007
timeFrame: Day 14
measure: Pharmacokinetic Parameter: Cav (Average Plasma Concentration) of E2007
timeFrame: Day 14
measure: Pharmacokinetic Parameter: Peak-to-trough Fluctuation (PTF) of E2007
timeFrame: Day 14
measure: Pharmacokinetic Parameter: Observed Accumulation Ratio (Rac) of E2007
timeFrame: Day 14
Secondary outcomes:
measure: Change from Baseline of Bond and Lader Scale
timeFrame: Baseline, Day 28 and Day 42
measure: Change from Baseline of Peak Saccadic Velocity (PSV)
timeFrame: Baseline, Day 28, Day 42
measure: Number of Particpants receiving other Anti-epileptic agents During Treatment
timeFrame: Day 1 and Day 14
measure: Percent Change from Baseline of Failed Saccades
timeFrame: Baseline, Day 28, Day 42
measure: Mean trough concentrations of E2007
timeFrame: Day 7, Day 21, and Day 28
measure: Number of seizures
timeFrame: Baseline (Day-1) to Day 42
measure: The Clinical Global Impression of Change
timeFrame: Day 28
Other outcomes:
Locations:
city: Hennigsdorf
country: Germany
facility: 3ClinicalResearch AG
Study officials:
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.