Back to results

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

Primary Purpose

Epilepsy

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Perampanel

Placebo

About this trial

This is an interventional treatment trial for Epilepsy

Eligibility Criteria

12 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

Perampenal (Core Study)

Placebo (Core Study)

Perampanel (Extension Phase)

Arm 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.

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

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

The Power of Attention domain (one of the 5 CDR System cognitive domains) was a measure of focused attention and information processing, comprised of the 3 CDR System attention tasks: the simple reaction time, choice reaction time and digit vigilance tasks. Z-scores were calculated for each domain by subtracting each participant's domain score from the normative population mean of that domain and dividing the result by the standard deviation (SD) of the normative population mean. Z-scores were converted into T-scores by multiplying by 50 and adding 50. Power of Attention were also multiplied by -1, so that for all domains, greater T-scores reflected superior cognitive function. T-scores ranged from 0 to 100, with a mean of 50 and an SD of 10. The CDR System Global Cognition score was created by adding the T-scores for the five domains. A decrease in the score of Power of Attention indicated improvement in cognitive function and a negative change reflects impairment from baseline.

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

The Continuity of Attention domain (one of the 5 CDR System cognitive domains) was a measure of sustained attention, comprised of the accuracy scores from 2 of the CDR System attention tasks: choice reaction time and digit vigilance. Z-scores were calculated for this domain using normative data from the CDR System database for the age range of the study population. Specifically, Z-scores were calculated by subtracting each participant's domain score from the normative population mean of that domain and dividing the result by the SD of the normative population mean. Z-scores were converted into T-scores by multiplying by 50 and adding 50. Greater T-scores reflected superior cognitive function and a negative change from baseline reflects impairment compared to baseline. T-scores ranged from 0 to 100, with a mean of 50 and an SD of 10.

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

The Quality of Episodic Secondary Memory domain was a measure of the capability of individuals to encode, store, and subsequently retrieve verbal and nonverbal information in episodic (or declarative) memory; what was meant by memory in everyday terminology. This measure was derived by summing the scores from the 4 tasks: immediate and delayed word recall, word recognition, and picture recognition. Z-scores were calculated by subtracting each participant's domain score from the normative population mean of that domain and dividing the result by the SD of the normative population mean. Z-scores were converted into T-scores by multiplying by 50 and adding 50. Greater T-scores reflected superior cognitive function. T-scores ranged from 0 to 100, with a mean of 50 and an SD of 10. A high score reflects a good ability to store, hold and retrieve information of an episodic nature (i.e. an event or a name) and a negative change from baseline reflects impairment compared to baseline.

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

The Quality of Working Memory domain (one of the 5 CDR System cognitive domains) was a measure of reflecting how well individuals can hold numeric and spatial information 'on line' in working memory. Z-scores were calculated by subtracting each participant's domain score from the normative population mean of that domain and dividing the result by the SD of the normative population mean. Z-scores were converted into T-scores by multiplying by 50 and adding 50. Greater T-scores reflected superior cognitive function. T-scores ranged from 0 to 100, with a mean of 50 and an SD of 10. A higher score reflects a good working memory and a negative change from baseline reflects impairment compared to the baseline assessment.

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

The Speed of Memory domain (one of the 5 CDR System cognitive domains) was a measure, which reflects the time taken to accurately retrieve information from working and episodic memory. Z-scores were calculated for this domain using normative data from the CDR System database for the age range of the study population. Specifically, Z-scores were calculated by subtracting each participant's domain score from the normative population mean of that domain and dividing the result by the SD of the normative population mean. Z-scores were converted into T-scores by multiplying by 50 and adding 50. Speed of Memory were also multiplied by -1, so that for all domains, greater T-scores reflected superior cognitive function and a negative change from baseline reflects impairment compared to the baseline assessment. T-scores ranged from 0 to 100, with a mean of 50 and an SD of 10.

Percentage of Participants Who Experienced 50% or More Decrease in Seizure Frequency (Core Study)

A responder was a participant who experienced a 50% or greater reduction in seizure frequency compared to the baseline of the Randomization Phase.

Percent Change From Baseline in Seizure Frequency Per 28 Days During the Treatment Duration of the Randomization Phase (Core Study)

Seizure frequency was based on overall number of seizures obtained by summing the 4 seizure types (all partial seizure types, that is, simple partial without motor signs, simple partial with motor signs, complex partial, and complex partial with secondary generalization) collected via the patient diary over a particular time interval and re-scaled to 28 days window.

Number of Participants Who Achieved Seizure-Free Status During the Maintenance Period and the Last 28 Days of the Maintenance Period During the Randomization Phase (Core Study)

Number of Participants who were seizure free, were assessed.

Percent Change From Baseline in Seizure Frequency Per 28 Days Over the Perampanel Duration Exposure (Extension Phase)

The median percent change in total partial onset seizure frequency per 28 days during the Extension Phase relative to the Pre-perampanel Baseline from Week 1 of perampanel treatment through successive 13-week intervals (Weeks 1 to 13 for subjects with any data, Weeks 1 to 26 for subjects with exposure of more than 13 weeks, Weeks 1 to 39 for subjects with exposure of more than 26 weeks, and Week 1 to 52 for subjects with exposure of more than 52 weeks) are presented. The perampanel exposure duration starts from the first perampanel dose (in the Core Study for subjects previously randomized to perampanel or Extension Phase for subjects previously randomized to placebo) to the last perampanel dose in the Extension Phase.

Percentage of Participants Who Experienced 50% or More Decrease in Seizure Frequency Over the Perampanel Duration Exposure (Extension Phase)

A responder was a participant who experienced a 50% or greater reduction in seizure frequency per 28 days from pre-perampanel. The percentage of responders from Week 1 of perampanel treatment through successive 13-week intervals (Weeks 1 to 13 for subjects with any data, Weeks 1 to 26 for subjects with exposure of more than 13 weeks, Weeks 1 to 39 for subjects with exposure of more than 26 weeks, and Week 1 to 52 for subjects with exposure of more than 52 weeks) are presented. The perampanel exposure duration starts from the first perampanel dose (in the Core Study for subjects previously randomized to perampanel or Extension Phase for subjects previously randomized to placebo) to the last perampanel dose in the Extension Phase.

Mean Change From Baseline to End of Treatment in Cognition Drug Research (CDR) System Global Cognition Score (Extension Phase)

The CDR System Global Cognitive 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). Domain scores were normalized to mean of 50 and standard deviation of 10 before taking the average. The scale ranged from 0 to 100. An increase in the Global Cognitive Score indicates improvement, while a decrease indicates worsening in cognitive function. The perampanel exposure duration starts from the first perampanel dose (in the Core Study for subjects previously randomized to perampanel or Extension Phase for subjects previously randomized to placebo) to the last perampanel dose in the Extension Phase.

Mean Change From Baseline in CDR System Global Cognition Score Over Time (Extension Phase)

The CDR System Global Cognitive 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). Domain scores were normalized to mean of 50 and SD of 10 before taking the average. The scale ranged from 0 to 100. An increase in the Global Cognitive Score indicates improvement, while a decrease indicates worsening in cognitive function. The data is presented as CDR System Global Cognitive scores at specific intervals (Week 9 for subjects with exposure of more than 9 weeks, Week 19 for subjects with exposure of more than 19 weeks, Week 30 for subjects with exposure of more than 26 weeks, Week 39 for subjects with exposure of more than 39 weeks, and Week 52 for subjects with exposure of more than 52 weeks).

Mean Change From Baseline by Visits in CDR System Domain T-Scores (Extension Phase)

The Cognitive measure scores are presented as T-Scores. T-Scores were normalized standard scores with mean of 50 and SD of 10 with an absolute range of 0-100. The T-Scores are based on the norms from healthy age-matched controls from the CDR System database. Cohen's d-effect sizes were used to estimate the clinical relevance of a change in a parameter. A change in a score of 0.2 SD was defined by Cohen as a small effect size, 0.5 SD a medium effect size and 0.8 SD was considered a large effect size. An increase in the T-scores indicates improvement while a decrease in T-scores indicates worsening. Wk = Week and EOT=End of Treatment. The perampanel exposure duration starts from the first perampanel dose (in the Core Study for subjects previously randomized to perampanel or Extension Phase for subjects previously randomized to placebo) to the last perampanel dose in the Extension Phase.

Mean Change From Baseline in CDR System Domain T-Score Over Time: Power of Attention (Extension Phase)

The Cognitive measure scores are presented as T-Scores at specific intervals (Week 9 for subjects with exposure of more than 9 weeks, Week 19 for subjects with exposure of more than 19 weeks, Week 30 for subjects with exposure of more than 26 weeks, Week 39 for subjects with exposure of more than 39 weeks, and Week 52 for subjects with exposure of more than 52 weeks). T-Scores were normalized standard scores with mean of 50 and SD of 10 with an absolute range of 0-100. The T-Scores are based on the norms from healthy age-matched controls from the CDR System database. Cohen's d-effect sizes were used to estimate the clinical relevance of a change in a parameter. A change in a score of 0.2 SD was defined by Cohen as a small effect size, 0.5 SD a medium effect size and 0.8 SD was considered a large effect size. An increase in the T-scores indicates improvement while a decrease in T-scores indicates worsening.

Mean Change From Baseline in CDR System Domain T-Score Over Time: Continuity of Attention (Extension Phase)

Mean Change From Baseline in CDR System Domain T-Score Over Time: Quality of Episodic Secondary Memory (Extension Phase)

Mean Change From Baseline in CDR System Domain T-Score Over Time: Quality of Working Memory (Short Term) (Extension Phase)

The cognitive measure scores are presented as T-Scores at specific intervals (Week 9 for participants with exposure of more than 9 weeks, Week 19 for participants with exposure of more than 19 weeks, Week 30 for participants with exposure of more than 26 weeks, Week 39 for participants with exposure of more than 39 weeks, and Week 52 for participants with exposure of more than 52 weeks). T-Scores were normalized standard scores with mean of 50 and SD of 10 with an absolute range of 0-100. The T-Scores are based on the norms from healthy age-matched controls from the CDR System database. Cohen's d-effect sizes were used to estimate the clinical relevance of a change in a parameter. A change in a score of 0.2 SD was defined by Cohen as a small effect size, 0.5 SD a medium effect size and 0.8 SD was considered a large effect size. An increase in the T-scores indicates improvement while a decrease in T-scores indicates worsening.

Mean Change From Baseline in CDR System Domain T-Score Over Time: Speed of Memory (Extension Phase)

Change From Baseline to End of Treatment in Controlled Oral Word Association Test Scores (COWAT) (Extension Phase)

The COWAT test measured the executive function of the frontal lobe and consisted of examinations of category/meaning fluency and letter/phoneme fluency. It consisted of 2 parts which included the Letter Fluency task and the Category Fluency task. For the Letter Fluency task, the participant was given one minute to list as many words as they could which began with a given letter from the following set of 3 letters: F, A, and L. The number of correct words from the 3 sets comprised the Letter Fluency score. For the Category Fluency task, the participant was given one minute to list as many words as they could which belonged to a given category. The number of correct words comprised the Category Fluency score. Total score was calculated as sum of acceptable words generated. The scale ranged from 0-90, with higher scores indicating improvement in language.

Change From Baseline to End of Treatment in Time to Complete Lafayette Grooved Pegboard Test (LGPT) (Extension Phase)

The LGPT test measured visuomotor skills. This test was a manipulative dexterity test that consisted of a metal matrix of 25 holes with randomly positioned slots. The participant was required to insert 25 grooved pegs into the holes. The task was completed once for each hand; firstly, using the dominant hand followed by the non-dominant hand. The task was timed and the scores were the time taken for the participant to complete all 25 pegs for each hand. If the test cannot be completed within 300 seconds, 300 seconds were recorded for the time. An increase in score (longer time) indicated worsening of visuomotor skills. The time to complete test is presented as mean seconds +/- SD.

Mean Change From Baseline in Bone Age Minus Age (Months) From Hand X-ray (Extension Phase)

Bone age was measured using hand X-ray. The mean change from Baseline in bone age (months) minus age (months) from the hand x-ray was assessed. "+" means bone age is older than age and "-" means bone age is younger than age.

Change From Baseline to End of Treatment (EOT) for the Tanner Stage

The effect of perampanel on growth and development in adolescents (male and female), including sexual development was measured using Tanner scale. The scale defined physical measurements of development based on external primary and secondary sex characteristics, such as the size of the breasts, genitals, testicular volume and development of pubic hair. Tanner scale consisted of 5 scales from I to V (1: pre-pubertal to 5: adult). Data is reported as the change from Baseline to End of Treatment for the Tanner Stage.

Full Information

NCT ID

NCT01161524

First Posted

July 12, 2010

Last Updated

April 24, 2019

Sponsor

Eisai Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01161524

Brief Title

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

Official Title

A Randomized, Double-blind, Placebo-controlled, Parallel-group Study With an Open-label Extension Phase to Evaluate the Effect of Perampanel (E2007) on Cognition, Growth, Safety, Tolerability, and Pharmacokinetics When Administered as an Adjunctive Therapy in Adolescents (12 to Less Than 18 Years of Age) With Inadequately Controlled Partial-onset Seizures

Study Type

Interventional

2. Study Status

Record Verification Date

November 2015

Overall Recruitment Status

Completed

Study Start Date

September 2010 (Actual)

Primary Completion Date

June 2013 (Actual)

Study Completion Date

November 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eisai Inc.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Epilepsy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

133 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Perampenal (Core Study)

Arm Type

Experimental

Arm 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.

Arm Title

Placebo (Core Study)

Arm Type

Placebo Comparator

Arm Description

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

Arm Title

Perampanel (Extension Phase)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Perampanel

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Matching Placebo taken once daily.

Primary Outcome Measure Information:

Title

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

Description

Time Frame

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

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

Baseline and Week 19

Title

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

Description

Time Frame

Baseline and Week 19

Title

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

Description

Time Frame

Baseline and Week 19

Title

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

Description

Time Frame

Baseline and Week 19

Title

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

Description

Time Frame

Baseline and Week 19

Title

Percentage of Participants Who Experienced 50% or More Decrease in Seizure Frequency (Core Study)

Description

A responder was a participant who experienced a 50% or greater reduction in seizure frequency compared to the baseline of the Randomization Phase.

Time Frame

From Baseline up to Week 19 LOCF

Title

Percent Change From Baseline in Seizure Frequency Per 28 Days During the Treatment Duration of the Randomization Phase (Core Study)

Description

Time Frame

Baseline and Week 19 LOCF

Title

Number of Participants Who Achieved Seizure-Free Status During the Maintenance Period and the Last 28 Days of the Maintenance Period During the Randomization Phase (Core Study)

Description

Number of Participants who were seizure free, were assessed.

Time Frame

13 Week Maintenance Period

Title

Percent Change From Baseline in Seizure Frequency Per 28 Days Over the Perampanel Duration Exposure (Extension Phase)

Description

Time Frame

Week 1-13, Week 14-26, Week 27-39, and Week 40-52

Title

Percentage of Participants Who Experienced 50% or More Decrease in Seizure Frequency Over the Perampanel Duration Exposure (Extension Phase)

Description

Time Frame

Week 1-13, Week 14-26, Week 27-39, and Week 40-52

Title

Mean Change From Baseline to End of Treatment in Cognition Drug Research (CDR) System Global Cognition Score (Extension Phase)

Description

Time Frame

Baseline, Week 9, Week 19, Week, 30, Week 39, Week 52, and End of Treatment (defined as the last nonmissing value after date of first perampanel dose up to 14 days after date of last dose)

Title

Mean Change From Baseline in CDR System Global Cognition Score Over Time (Extension Phase)

Description

The CDR System Global Cognitive 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). Domain scores were normalized to mean of 50 and SD of 10 before taking the average. The scale ranged from 0 to 100. An increase in the Global Cognitive Score indicates improvement, while a decrease indicates worsening in cognitive function. The data is presented as CDR System Global Cognitive scores at specific intervals (Week 9 for subjects with exposure of more than 9 weeks, Week 19 for subjects with exposure of more than 19 weeks, Week 30 for subjects with exposure of more than 26 weeks, Week 39 for subjects with exposure of more than 39 weeks, and Week 52 for subjects with exposure of more than 52 weeks).

Time Frame

Baseline, Week 9, Week 19, Week, 30, Week 39, and Week 52

Title

Mean Change From Baseline by Visits in CDR System Domain T-Scores (Extension Phase)

Description

Time Frame

Baseline, Week 9, Week 19, Week 30, Week 39, Week 52, and EOT (defined as the last nonmissing value after date of first dose up to 14 days after date of last dose)

Title

Mean Change From Baseline in CDR System Domain T-Score Over Time: Power of Attention (Extension Phase)

Description

Time Frame

Baseline, Week 9, Week 19, Week 30, Week 39, and Week 52

Title

Mean Change From Baseline in CDR System Domain T-Score Over Time: Continuity of Attention (Extension Phase)

Description

Time Frame

Baseline, Week 9, Week 19, Week, 30, Week 39, and Week 52

Title

Mean Change From Baseline in CDR System Domain T-Score Over Time: Quality of Episodic Secondary Memory (Extension Phase)

Description

Time Frame

Baseline, Week 9, Week 19, Week 30, Week 39, and Week 52

Title

Mean Change From Baseline in CDR System Domain T-Score Over Time: Quality of Working Memory (Short Term) (Extension Phase)

Description

Time Frame

Baseline, Week 9, Week 19, Week, 30, Week 39, and Week 52

Title

Mean Change From Baseline in CDR System Domain T-Score Over Time: Speed of Memory (Extension Phase)

Description

Time Frame

Baseline, Week 9, Week 19, Week, 30, Week 39, and Week 52

Title

Change From Baseline to End of Treatment in Controlled Oral Word Association Test Scores (COWAT) (Extension Phase)

Description

Time Frame

From Baseline up to Week 52 or up to EOT (defined as the last nonmissing value after date of first dose up to 14 days after date of last dose)

Title

Change From Baseline to End of Treatment in Time to Complete Lafayette Grooved Pegboard Test (LGPT) (Extension Phase)

Description

Time Frame

From Baseline up to Week 52 or up to EOT (defined as the last nonmissing value after date of first dose up to 14 days after date of last dose)

Title

Mean Change From Baseline in Bone Age Minus Age (Months) From Hand X-ray (Extension Phase)

Description

Time Frame

From Baseline up to Week 52 or up to EOT (defined as the last nonmissing value after date of first dose up to 14 days after date of last dose)

Title

Change From Baseline to End of Treatment (EOT) for the Tanner Stage

Description

Time Frame

From Baseline up to Week 52 or EOT (defined as the last nonmissing value after date of first dose up to 14 days after date of last dose)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Maximum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Haichen Yang, M.D., M.A.

Organizational Affiliation

Study Director

Official's Role

Study Director

Facility Information:

City

Aurora

State/Province

Colorado

Country

United States

City

Gulf Breeze

State/Province

Florida

Country

United States

City

Orlando

State/Province

Florida

Country

United States

City

Tampa

State/Province

Florida

Country

United States

City

Indianapolis

State/Province

Indiana

Country

United States

City

Chesterfield

State/Province

Missouri

Country

United States

City

Gibbsboro

State/Province

New Jersey

Country

United States

City

Akron

State/Province

Ohio

Country

United States

City

Memphis

State/Province

Tennessee

Country

United States

City

Nashville

State/Province

Tennessee

Country

United States

City

Dallas

State/Province

Texas

Country

United States

City

Heidelberg

State/Province

Victoria

Country

Australia

City

Bruxelles

Country

Belgium

City

Leuven

Country

Belgium

City

Ottignies

Country

Belgium

City

Ostrava

Country

Czechia

City

Budapest

Country

Hungary

City

Debrecen

Country

Hungary

City

Miskolc

Country

Hungary

City

Bangalore

Country

India

City

Hyderabad

Country

India

City

Mangalore

Country

India

City

Nagpur

Country

India

City

New Delhi

Country

India

City

Pune

Country

India

City

Secunderabad

Country

India

City

Daegu

Country

Korea, Republic of

City

Seoul

Country

Korea, Republic of

City

Daugavpils

Country

Latvia

City

Riga

Country

Latvia

City

Valmiera

Country

Latvia

City

Gdansk

Country

Poland

City

Poznan

Country

Poland

City

Valencia

State/Province

Comunidad Valenciana

Country

Spain

City

Madrid

State/Province

Madrid, Communidad De

Country

Spain

City

Bangkok

Country

Thailand

City

Mueang Nonthaburi

Country

Thailand

12. IPD Sharing Statement

Citations:

PubMed Identifier

29653338

Citation

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.

Results Reference

derived

PubMed Identifier

26724782

Citation

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.

Results Reference

derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs