A Study With an Open-label Extension Phase to Evaluate the Effect of Perampanel (E2007) on Cognition, Growth, Safety, Tolerability, and Pharmacokinetics in Adolescents

Eisai

Status and phase: Completed; Phase 2

Conditions: Epilepsy

Treatments: Drug: Placebo; Drug: Perampanel

Study type: Interventional

Funder types: Industry

Identifiers

NCT01161524

E2007-G000-235

Details and patient eligibility

About

This study is designed to investigate the short- and long-term effects of perampanel on cognition, growth, and development in adolescents.

Full description

This study consisted of the Core Study and the Extension Part A and B. The Core Study consisted of 2 phases: Prerandomization and Randomization. The Prerandomization Phase lasted up to 1 week, during which participants were assessed for their eligibility to participate in the study. The Randomization Phase consisted of 3 periods: Titration (6 weeks), Maintenance (13 weeks), and Follow-up (4 weeks; only for those participants not rolling over into the Extension Phase). During the Core Study Titration and Maintenance Periods, participants were randomized into perampanel (2 to 12 mg per day) or placebo treatment groups in a 2:1 ratio within each of the age-matched categories (ie, greater than or equal to 12 to less than 15 and greater than or equal to 15 to less than 18).

The extension phase consisted of part A (Conversion Period - 6 weeks and Maintenance period - 25 weeks) and Part B (Optional Extension Phase -52 weeks). The maximum duration for participation in Part B was 52 weeks.

Enrollment: 133 patients

Sex: All

Ages: 12 to 18 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Considered reliable and willing to be available for the study duration and was able to record seizures and report adverse events (AEs) themselves or had a legal guardian or a caregiver who could record seizures and report AEs for them.
2. Understand the requirements of the Cognitive Drug Research (CDR) System tests and able to perform the tests appropriately at Visit 1.
3. Male or female, 12 to less than 18 years of age at the time of consent/assent
4. Had a diagnosis of epilepsy with partial-onset seizures with or without secondarily generalized seizures according to the International League Against Epilepsy's (ILAE) Classification of Epileptic Seizures (1981).
5. Diagnosis was established at least 6 months prior to Visit 1, by clinical history and an electroencephalogram (EEG) that was consistent with localization-related epilepsy; normal interictal EEGs were allowed provided that the subject met the other diagnosis criterion (ie, clinical history).
6. Had a brain imaging (e.g., magnetic resonance imaging [MRI] scan or computed tomography [CT]) within the 5 years prior to Visit 1 that ruled out a progressive cause of epilepsy.
7. Had at least 1 partial-onset seizure during the 4 weeks prior to Visit 1 despite a stable regimen of 1 to 3 concomitant antiepileptic drugs (AEDs).
8. Were currently being treated with stable doses of 1-3 AEDs. Only 1 inducer AED (either carbamazepine or phenytoin) out of the maximum of 3 AEDs was allowed.
9. Were on a stable dose of the same concomitant AED(s) for at least 4 weeks prior to Visit 1; in the case where a new AED regimen was initiated for a subject, the dose must have been stable for at least 8 weeks prior to Visit 1.
10. Female subjects of childbearing potential must had a negative serum human chorionic gonadotropin (beta-hCG) at Visit 1 and a negative urine pregnancy test prior to randomization at Visit 2. Female subjects of period of at least 60 days following administration of the last dose of study medication to commit to the consistent and correct use of a medically acceptable method of birth control (e.g., a double-barrier method [condom + spermicide, condom + diaphragm with spermicide]). Abstinence was considered an acceptable method of contraception on a case by case basis upon prior approval by the Medical Monitor.
11. Had an intelligence quotient (IQ) of greater than or equal to 70, using the Kaufman Brief Intelligence Test, second edition (KBIT-2).
12. Provided written informed consent signed by the legal guardian and a written assent from the subject prior to entering the study or undergoing any study procedures.

Extension Phase:

Had completed all scheduled visits up to and including Visit 8 in the Core Study Randomization Phase.

Exclusion criteria

1. Had a diagnosis of primary generalized epilepsies or seizures such as absences and/or myoclonic epilepsies.
2. Had current or a history of pseudo-seizures (psychogenic non-epileptic seizures [PNES]) within approximately 5 years prior to Visit 1.
3. Had a diagnosis of Lennox-Gastaut syndrome.
4. Had seizure clusters where individual seizures could not be counted.
5. Had a history of status epilepticus that required hospitalization during the 12 months prior to the Visit 1.
6. Had an unstable psychiatric diagnosis that could confound the investigator's ability to conduct the study or that could prevent completion of the protocol specified tests (e.g., significant suicide risk, including suicidal behavior and ideation 6 months prior to Visit 1, current psychotic disorder, or acute mania).
7. Had any concomitant illnesses/co-morbidities (e.g., autism, attention deficit hyperactivity disorder [ADHD]) at Visit 1 that could severely affect cognitive function during the course of the study.
8. Had previously participated in a clinical trial involving perampanel.
9. Had chronically or routinely use benzodiazepines and who have not discontinued the use at least 4 weeks prior to Visit 1.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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133 participants in 3 patient groups, including a placebo group

Perampenal (Core Study)

Experimental group

Description:

Participants received perampanel 2 mg per day and up-titrated weekly in 2-mg increments to a target dose range of 8 to 12 mg per day.

Treatment:

Drug: Perampanel

Placebo (Core Study)

Placebo Comparator group

Description:

Participants received matching placebo tablets once a day (6 tablets of placebo).

Treatment:

Drug: Placebo

Perampanel (Extension Phase)

Experimental group

Description:

During the Extension Phase, participants previously assigned to perampanel arm (Core Study) continued taking study medication at the dose achieved at the end of the Core Study once daily. Participants previously assigned to a placebo arm (Core Study) started perampanel dose at 2 mg/day and up-titrated weekly in 2-mg increments up to a maximum dose of 12 mg/day.

Treatment:

Drug: Perampanel