Perampanel as Adjunctive Therapy in Pediatrics With Partial Onset Seizures or Primary Generalized Tonic Clonic Seizures

NCT02849626 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: E2007-G000-3112014-002167-16
• Study Type: interventional
• Target: 180
• Locations: 12 countries
• Sites: 91

Brief Summary

This is an open-label, multicenter study with an Extension Phase to evaluate the safety and tolerability of perampanel oral suspension when administered as an adjunctive therapy in children (ages 4 to less than \[\<\] 12 years) with inadequately controlled partial onset seizures (POS) or primary generalized tonic clonic (PGTC) seizures.

Conditions

Partial-Onset or Primary Generalized Tonic-Clonic Seizures

Keywords

Partial-Onset Seizures; Primary Generalized Tonic-Clonic Seizures; Adjunctive Therapy; Epilepsy

Outcome Measures

Primary Outcomes (4)

• Percentage of Participants With Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs) for Total Group of Participants - Core Phase and Extension Phase A of This Study

  Baseline up to 4 weeks (follow up in Extension Phase A) after last dose of study drug in Extension Phase A at Week 52 (up to 56 weeks)

• Percentage of Participants With Treatment Emergent Markedly Abnormal Laboratory Values for Total Group of Participants- Core Phase and Extension Phase A of This Study

  Baseline up to 52 weeks

• Percentage of Participants With Abnormal Vital Sign Values for Total Group of Participants- Core Phase and Extension Phase A of This Study

  Pre-defined criteria of vital signs abnormalities: maximum (max.) increase or decrease from baseline in sitting/supine systolic blood pressure (SBP) of greater than or equal to (\>=) 20 or 40 millimeter of mercury (mmHg); maximum increase or decrease from baseline in sitting/supine diastolic blood pressure (DBP) \>=10 or 20 mmHg; increase or decrease from baseline in pulse rate (number of heart beats per minute \[bpm\]) of \>=15 or 30 bpm. Data for this outcome measure has been assessed and reported till Week 52.

  Baseline up to 52 weeks

• Percentage of Participants With Markedly Abnormal Electrocardiogram (ECG) Parameters for Total Group of Participants- Core Phase and Extension Phase A of This Study

  Baseline up to 52 weeks

Secondary Outcomes (30)

• Model Predicted Percent Change in Average Seizure Frequency Over 28 Days During Maintenance Period in Core Phase of This Study From Baseline- Assessed as Relationship With Average Steady State Plasma Concentration (Cav, ss) of Perampanel (518 ng/mL)

  Baseline, Week 23

• Overall Responder Probability For Non-Asian Participants With POS During Core Phase of This Study: Assessment Based on Relationship With Average Steady State Plasma Concentration (Cav, ss) of Perampanel

  Baseline up to 23 weeks

• Overall Responder Probability For Participants With PGTC Seizures During Core Phase of This Study: Assessment Based on Relationship With Average Steady State Plasma Concentration (Cav, ss) of Perampanel

  Baseline up to 23 weeks

• Number of Seizure Free Observations During Core Phase of This Study: Assessment Based on Relationship With Average Steady State Plasma Concentration (Cav, ss) of Perampanel

  Baseline up to Week 23

• Model Predicted Change From Baseline in Total Aldenkamp-Baker Neuropsychological Assessment Schedule (ABNAS) Score During Core Phase of This Study: Assessment Based on Relationship With Plasma Levels of Perampanel

  Baseline up to Week 23

Study Arms (1)

Perampanel

EXPERIMENTAL

Perampanel 0.5 milligrams per milliliter (mg/mL) oral suspension

Drug: Perampanel

Interventions

Perampanel DRUG

E2007

Perampanel

Eligibility Criteria

• Age: 4 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Have a diagnosis of epilepsy with POS with or without secondarily generalized (SG) seizures or PGTC seizures according to the International League Against Epilepsy's (ILAE) Classification of Epileptic Seizures (1981). A diagnosis should have been established at least 6 months prior to Visit 1 by clinical history and an electroencephalogram (EEG) that is consistent with the diagnosis; normal interictal EEGs will be allowed provided that the participant meets the other diagnosis criterion (that is, clinical history)
• Male or female participant, from age 4 to \<12 years at the time of informed consent/assent
• Have a minimum weight of 16 kilograms (kg) (35 pounds \[lb\])
• Have had a brain imaging (example, magnetic resonance imaging \[MRI\] scan or computed tomography \[CT\] before Visit 1 that ruled out a progressive cause of epilepsy)
• Are currently being treated with stable doses of 1 to a maximum of 3 approved antiepileptic drugs (AEDs). Doses must be stable for at least 4 weeks before to Visit 1; in the case where a new AED regimen has been initiated for a participant, the dose must be stable for at least 8 weeks prior to Visit 1. Only one EIAED (defined as carbamazepine, phenytoin, oxcarbazepine, or eslicarbazepine) out of the maximum of three AEDs is allowed (A vagal nerve stimulator \[VNS\] will be counted as one of the 3 allowed AEDs)

You may not qualify if:

• Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta human chorionic gonadotropin \[β-hCG\] or human chorionic gonadotropin \[hCG\] test with a minimum sensitivity of 25 International Units per liter \[IU/L\] or equivalent units of β-hCG or hCG). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug
• Females of childbearing potential who:
• Had unprotected sexual intercourse within 30 days before study entry and who do not agree to use a highly effective method of contraception (example, total abstinence, an intrauterine device, a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period or for 28 days after study drug discontinuation. If a highly effective method is not appropriate or acceptable for the participant, then the participant may use a medically effective method (example, a double barrier method such as condom plus diaphragm with spermicide)
• Are currently abstinent, and do not agree to use a double-barrier method (as described above) or refrain from being sexually active during the study period or for 28 days after study drug discontinuation
• Are using hormonal contraceptives but are not on a stable dose of the same hormonal contraceptive product for at least 4 weeks before dosing and who do not agree to use the same contraceptive during the study or for 28 days after study drug discontinuation
• Current or history of pseudo-seizures (psychogenic nonepileptic seizures) within approximately 5 years before Visit 1
• Have a history of status epilepticus that required hospitalization during the 6 months before Visit 1
• Have an unstable psychiatric diagnosis that may confound participants' ability to participate in the study or that may prevent completion of the protocol-specified tests (example, significant suicide risk, including suicidal behavior and ideation within 6 months before Visit 1, current psychotic disorder, acute mania)
• Any suicidal ideation with intent with or without a plan within 6 months before Visit 2 (that is, answering "Yes" to questions 4 or 5 on the Suicidal Ideation section of the Columbia Suicide Severity Rating Scale \[C-SSRS\]) in participants aged 6 and above
• Are scheduled and/or confirmed to have epilepsy surgery within 6 months after Visit 1; however, those who have previously documented "failed" epilepsy surgery will be allowed
• Evidence of clinically significant disease (example, cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments
• Evidence of moderate or severe renal insufficiency as defined by estimated glomerular filtration rates (eGFRs) of 31 to \<60 milliliters per minute (mL/min) and \<30 mL/min, respectively
• Evidence of significant active hepatic disease. Stable elevation of liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) due to concomitant medication(s), will be allowed if they are less than 3 times the upper limit of normal (ULN)
• Evidence of significant active hematological disease; white blood cell (WBC) count equal or less than (=\<) 2500 per (/) microliter (µL) (2.50 1 constant \[E\]+09/liter \[L\]) or an absolute neutrophil count =\<1000/µL (1.00 1E+09/L)
• Clinically significant electrocardiogram (ECG) abnormality, including prolonged corrected QT interval (QTc) defined as greater than (\>) 450 milliseconds (msec)

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (91)

Facility #1

Little Rock, Arkansas, United States

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Palo Alto, California, United States

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Aurora, Colorado, United States

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Gulf Breeze, Florida, United States

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Loxahatchee Groves, Florida, United States

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Orlando, Florida, United States

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Atlanta, Georgia, United States

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Savannah, Georgia, United States

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Boise, Idaho, United States

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Chicago, Illinois, United States

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Urbana, Illinois, United States

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Ames, Iowa, United States

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Wichita, Kansas, United States

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Lexington, Kentucky, United States

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Lexington, Kentucky, United States

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New Orleans, Louisiana, United States

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Duluth, Minnesota, United States

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Kansas City, Missouri, United States

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Henderson, Nevada, United States

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Hackensack, New Jersey, United States

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Voorhees Township, New Jersey, United States

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Brooklyn, New York, United States

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Winston-Salem, North Carolina, United States

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Cleveland, Ohio, United States

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Memphis, Tennessee, United States

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Austin, Texas, United States

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San Antonio, Texas, United States

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Tacoma, Washington, United States

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Milwaukee, Wisconsin, United States

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Pulderbos, Antwerpen, Belgium

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Ottignies, Brabant Wallon, Belgium

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Brussels, Brussels Capital, Belgium

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La Louvière, Hainaut, Belgium

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Brussels, Belgium

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Calgary, Alberta, Canada

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Montreal, Quebec, Canada

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Ostrava, Czechia

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Prague, Czechia

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Marseille, Bouches-du-Rhone, France

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Lille, France

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Marseille, France

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Paris, France

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Paris, France

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Strasbourg, France

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Toulouse, France

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Budapest, Hungary

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Budapest, Hungary

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Miskolc, Hungary

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Pécs, Hungary

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Mantova, Lombardy, Italy

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Calambrone, Tuscany, Italy

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Bologna, Italy

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Florence, Italy

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Milan, Italy

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Eisai Trial Site #1

Sapporo, Hokkaido, Japan

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Zentsujichó, Kagawa-ken, Japan

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Sendai, Miyagi, Japan

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Hamamatsu, Shizuoka, Japan

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Fukuoka, Japan

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Gifu, Japan

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Hakodate-shi, Japan

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Hiroshima, Japan

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Izumi, Japan

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Kobe, Japan

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Kumamoto, Japan

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Nagoya, Japan

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Nara, Japan

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Niigata, Japan

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Okayama, Japan

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Osaka, Japan

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Ōmura, Japan

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Sagamihara, Japan

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Sapporo, Japan

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Shizuoka, Japan

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Yamagata, Japan

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Yokohama, Japan

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Riga, Latvia

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Poznan, Greater Poland Voivodeship, Poland

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Gdansk, Pomeranian Voivodeship, Poland

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Kielce, Świętokrzyskie Voivodeship, Poland

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Daegu, South Korea

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Daejeon, South Korea

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Seoul, South Korea

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Seoul, South Korea

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Seoul, South Korea

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Esplugues de Llobregat, Barcelona, Spain

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Barcelona, Spain

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Barcelona, Spain

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Madrid, Spain

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Seville, Spain

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Valencia, Spain

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Related Publications (2)

• Trigg A, Brohan E, Cocks K, Jones A, Tahami Monfared AA, Chabot I, Meier G, Campbell R, Li H, Ngo LY. Health-related quality of life in pediatric patients with partial onset seizures or primary generalized tonic-clonic seizures receiving adjunctive perampanel. Epilepsy Behav. 2021 May;118:107938. doi: 10.1016/j.yebeh.2021.107938. Epub 2021 Apr 8.

  PMID: 33839450 DERIVED

• Fogarasi A, Flamini R, Milh M, Phillips S, Yoshitomi S, Patten A, Takase T, Laurenza A, Ngo LY. Open-label study to investigate the safety and efficacy of adjunctive perampanel in pediatric patients (4 to <12 years) with inadequately controlled focal seizures or generalized tonic-clonic seizures. Epilepsia. 2020 Jan;61(1):125-137. doi: 10.1111/epi.16413. Epub 2020 Jan 7.

  PMID: 31912493 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 Medical Information
• Organization: Eisai Inc.

esi_medinfo@eisai.com

+1-888-274-2378

Study Officials

• Eisai Medical Information

  Eisai Inc.

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2016
• First Posted: July 29, 2016
• Study Start: November 16, 2016
• Primary Completion: February 5, 2019
• Study Completion: December 6, 2021
• Last Updated: October 28, 2022
• Results First Posted: April 6, 2020

Record last verified: 2022-10

Locations

LA (1); PL (3); CZ (2); HU (4); BE (5); IT (5); ES (6); FR (7); JP (22); KR (5); CA (2); US (29)