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

NCT01161524 | Completed Phase 2 Results DMC

• 1 other identifier: E2007-G000-235
• Study Type: interventional
• Target: 133
• Locations: 11 countries
• Sites: 37

Brief Summary

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

Conditions

Epilepsy

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Week 19 in Cognition Drug Research (CDR) System Global Cognition Score (Core Study)

  The CDR System Global Cognitive score was derived from the average of 5 CDR System cognitive domain scores (Power of Attention, Continuity of Attention, Quality of Episodic Memory, Quality of Working Memory, and Speed of Memory). The domain scores were normalized to mean of 50 and standard deviation of 10 before taking the average. The scale ranged from 0 - 100. An increase in the Global Cognitive Score indicates improvement, while a decrease indicates worsening in cognitive function.

  Baseline (Visit 2/Week 0 Evaluation) and Week 19 LOCF (last observation carried forward)

Secondary Outcomes (22)

• Change From Baseline at Week 19 in the Power of Attention T-score in the Randomization Phase (Core Study)

  Baseline and Week 19

• Change From Baseline at Week 19 in the Continuity of Attention T-score in the Randomization Phase (Core Study)

  Baseline and Week 19

• Change From Baseline at Week 19 in the Quality of Episodic Secondary Memory T-score in the Randomization Phase (Core Study)

  Baseline and Week 19

• Change From Baseline at Week 19 in the Quality of Working Memory (Short Term) T-score in the Randomization Phase (Core Study)

  Baseline and Week 19

• Change From Baseline at Week 19 in the Speed of Memory T-score in the Randomization Phase (Core Study)

  Baseline and Week 19

Study Arms (3)

Perampenal (Core Study)

EXPERIMENTAL

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.

Drug: Perampanel

Placebo (Core Study)

PLACEBO COMPARATOR

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

Drug: Placebo

Perampanel (Extension Phase)

EXPERIMENTAL

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.

Drug: Perampanel

Interventions

Perampanel DRUG

2 mg titrated up to 8-12 mg maximum; taken once daily.

Perampanel (Extension Phase); Perampenal (Core Study)

Placebo DRUG

Matching Placebo taken once daily.

Placebo (Core Study)

Eligibility Criteria

• Age: 12 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• Understand the requirements of the Cognitive Drug Research (CDR) System tests and able to perform the tests appropriately at Visit 1.
• Male or female, 12 to less than 18 years of age at the time of consent/assent
• 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).
• 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).
• 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.
• 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).
• 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.
• 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.
• 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.
• Had an intelligence quotient (IQ) of greater than or equal to 70, using the Kaufman Brief Intelligence Test, second edition (KBIT-2).
• 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.

You may not qualify if:

• Had a diagnosis of primary generalized epilepsies or seizures such as absences and/or myoclonic epilepsies.
• Had current or a history of pseudo-seizures (psychogenic non-epileptic seizures \[PNES\]) within approximately 5 years prior to Visit 1.
• Had a diagnosis of Lennox-Gastaut syndrome.
• Had seizure clusters where individual seizures could not be counted.
• Had a history of status epilepticus that required hospitalization during the 12 months prior to the Visit 1.
• 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).
• 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.
• Had previously participated in a clinical trial involving perampanel.
• Had chronically or routinely use benzodiazepines and who have not discontinued the use at least 4 weeks prior to Visit 1.

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (37)

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Aurora, Colorado, United States

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Gulf Breeze, Florida, United States

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Orlando, Florida, United States

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Tampa, Florida, United States

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Indianapolis, Indiana, United States

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Chesterfield, Missouri, United States

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Gibbsboro, New Jersey, United States

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Akron, Ohio, United States

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Memphis, Tennessee, United States

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Nashville, Tennessee, United States

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Dallas, Texas, United States

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Heidelberg, Victoria, Australia

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Brussels, Belgium

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Leuven, Belgium

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Ottignies, Belgium

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Ostrava, Czechia

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Budapest, Hungary

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Debrecen, Hungary

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Miskolc, Hungary

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Bangalore, India

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Hyderabad, India

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Mangalore, India

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Nagpur, India

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New Delhi, India

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Pune, India

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Secunderabad, India

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Daugavpils, Latvia

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Riga, Latvia

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Valmiera, Latvia

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Gdansk, Poland

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Poznan, Poland

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Daegu, South Korea

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Seoul, South Korea

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Madrid, Madrid, Communidad de, Spain

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Valencia, Valencia, Spain

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Bangkok, Thailand

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Nonthaburi, Thailand

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Related Publications (3)

• Bresnahan R, Hill RA, Wang J. Perampanel add-on for drug-resistant focal epilepsy. Cochrane Database Syst Rev. 2023 Apr 14;4(4):CD010961. doi: 10.1002/14651858.CD010961.pub2.

  PMID: 37059702 DERIVED

• Pina-Garza JE, Lagae L, Villanueva V, Renfroe JB, Laurenza A, Williams B, Kumar D, Meador KJ. Long-term effects of adjunctive perampanel on cognition in adolescents with partial seizures. Epilepsy Behav. 2018 Jun;83:50-58. doi: 10.1016/j.yebeh.2018.03.029. Epub 2018 Apr 10.

  PMID: 29653338 DERIVED

• Meador KJ, Yang H, Pina-Garza JE, Laurenza A, Kumar D, Wesnes KA. Cognitive effects of adjunctive perampanel for partial-onset seizures: A randomized trial. Epilepsia. 2016 Feb;57(2):243-51. doi: 10.1111/epi.13279. Epub 2016 Jan 1.

  PMID: 26724782 DERIVED

MeSH Terms

Conditions

Epilepsy

Interventions

perampanel

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Eisai Call Center
• Organization: Eisai Inc.

888-422-4743

Study Officials

• Haichen Yang, M.D., M.A.

  Study Director

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2010
• First Posted: July 13, 2010
• Study Start: September 1, 2010
• Primary Completion: June 1, 2013
• Study Completion: November 1, 2014
• Last Updated: May 15, 2019
• Results First Posted: May 15, 2019

Record last verified: 2015-11

Locations

CZ (1); LA (3); KR (2); AU (1); HU (3); IN (7); BE (3); PL (2); ES (2); TH (2); US (11)