PERAMPANEL for Childhood epilepsy | Epilepsy

Inclusion criteria

• {"criterion_text":"- Male or female subject, from age 1 month to less than 18 years for Cohort 1, or age 1 month to less than 2 years for Cohort 2 at the time of informed consent/assent. Subjects below the age of 1 year must have been at least 36 weeks of gestational age at birth. (revised per Amendments 01 and 02)\n- Have a diagnosis of epilepsy with a pediatric epileptic syndrome (Cohort 1) or epilepsy with POS with or without secondary generalization (Cohort 2) according to the International League against Epilepsy (ILAE) Classification of Epileptic Seizures (1981). The eligibility criteria for the 2 cohorts are not mutually exclusive as a subject may experience POS as part of an epilepsy syndrome; these subjects are eligible for Cohort 1 if: (1) they are 2 to less than 18 years of age; or (2) they are 1 month to less than 2 years of age AND Cohort 2 is filled. Diagnosis must have been established by clinical history and an EEG that is consistent with the diagnosis; normal interictal EEGs will be allowed provided that the subject meets the other diagnosis criterion (ie, clinical history).\n- Subjects must have had equal or greater than 4 seizures over the 4-week interval prior to Visit 2. For Cohort 1, all seizures except simple POS without motor signs are counted toward this inclusion. For Cohort 2, only simple POS with motor signs, complex POS, and complex POS with secondary generalization are counted toward this inclusion for POS.\n- Absence of any progressive cause of epilepsy that has been confirmed clinically or based on brain imaging (eg, magnetic resonance imaging [MRI] scan, computed tomography [CT], or ultrasound [only for subjects <1 year old]). (revised per Amendment 02).\n- Are currently being treated with stable doses of 1 to a maximum of 4 approved AEDs. A prescription medical marijuana (including products containing cannabidiol) is counted as 1 of the maximum of 4 allowed AEDs; however, it cannot be the only concomitant AED if this product is not an approved AED in the country where the study site is located. Doses must be stable for at least 4 weeks (at least 2 weeks for subjects <6 months old) before Visit 1; only 1 enzyme-inducing AED (EIAED) (defined as carbamazepine, phenytoin, oxcarbazepine, or eslicarbazepine) out of the maximum of 4 AEDs is allowed. (revised per Amendment 01)."}

Exclusion criteria

• {"criterion_text":"- Females who are breastfeeding or pregnant at Screening/Baseline (as documented by a positive beta-human chorionic gonadotropin [β-hCG] or human chorionic gonadotropin [hCG] test with a minimum sensitivity of 25 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 1st dose of study drug.\n- Evidence of significant active hepatic disease. Stable elevation of liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) due to concomitant medications, will be allowed if they are less than 3 times the upper limit of normal (ULN).\n- Evidence of significant active hematological disease; white blood cell (WBC) count equal or less than 2500/μL (2.50 1E+09/L), or an absolute neutrophil count equal or less than 1000/μL (1.00 1E+09/L).\n- Clinically significant ECG abnormality, including Fridericia prolonged corrected QT interval (QTcF) defined as greater than 450 msec.\n- Have a progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors.\n- Multiple drug allergies or a severe drug reaction to AEDs, including dermatological (eg, Stevens-Johnson syndrome), hematological, or organ toxicity reactions.\n- Concomitant use of felbamate as an AED for less than 2 years or where the dose has not been stable for at least 8 weeks before Visit 1. They must not have a history of WBC count below equal or less than 2500/μL (2.50 1E+09/L), platelets below 100,000, liver function tests above 3 times the ULN, or other indication of hepatic or bone marrow dysfunction while receiving felbamate. If subjects received felbamate in the past, it must have been discontinued 8 weeks before Visit 1 to be eligible for study participation.\n- Concomitant or recent (within last 5 months before Visit 1) use of vigabatrin or any evidence of vigabatrin-associated clinically significant vision abnormality.\n- Benzodiazepines for any indications other than epilepsy (eg, anxiety/sleep disorders) prohibited from 1 month before Visit 1 and during the study. Benzodiazepines for seizure control and as rescue medication are allowed. (revised per Amendments 01 and 02)\n- A vagal nerve stimulator (VNS), responsive neurostimulator (RNS), or deep brain stimulator (DBS) implanted less than 5 months before Visit 1 or changes in parameter less than 4 weeks before Visit 1 (or thereafter during the study).\n- On a ketogenic diet for which the diet is not stable regimen for at least 4 weeks before Visit 1.\n- Females of childbearing potential who: • Within 28 days before study entry, did not use a combination of a barrier method with a highly effective method of contraception, which includes any of the following: (revised per Amendment 01) o Total abstinence (if it is their preferred and usual lifestyle). o An intrauterine device or intrauterine hormone-releasing system (IUS). o A contraceptive implant. o An oral contraceptive (with additional barrier method). Subject must be on a stable dose of the same oral contraceptive product for at least 28 days before dosing and throughout the study and for 28 days after study drug discontinuation. o Have a vasectomized partner with confirmed azoospermia. Do not agree to use a combination of a barrier method with a highly effective method of contraception (as described above) throughout the entire study period and for 28 days after study drug discontinuation. (revised per Amendment 01). For sites outside of the EU, it is permissible that if a highly effective method of contraception is not appropriate or acceptable to the subject, then the subject must agree to use a medically acceptable method of contraception, ie, double-barrier methods of contraception such as latex or synthetic condom plus diaphragm or cervical/vault cap with spermicide. NOTE: All postpuberty females should be considered to be of childbearing potential unless they have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing).\n- History of or a concomitant medical condition that in the opinion of the investigator would preclude the subject’s participation in a clinical study or compromise the subject’s ability to safely complete the study.\n- Use of perampanel within 30 days before Visit 1, or perampanel was discontinued due to adverse reactions (perampanel-related) or lack of efficacy in case of previous exposure.\n- Subjects with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.\n- Have participated in a study involving administration of an investigational drug or device within 4 weeks before Visit 1, or within approximately 5 half-lives of the previous investigational compound, whichever is longer.\n- Hypersensitivity to the active substance or to any of the excipients of the study drug. (revised per Amendment 01)\n- Weight less than 4.0 kg at Visit 1. (revised per Amendment 02).\n- Current or history of pseudo-seizures (psychogenic nonepileptic seizures) within approximately 5 years before Visit 1.\n- Have a history of status epilepticus that required hospitalization during the 6 months before to Visit 1.\n- Have an unstable psychiatric diagnosis that may confound subjects’ ability to participate in the study or that may prevent completion of the protocol specified tests (eg, significant suicide risk, including suicidal behavior and ideation within 6 months before Visit 1, current psychotic disorder, acute mania).\n- Any suicidal ideation with intent with or without a plan within 6 months before Visit 2 (ie, answering “Yes” to questions 4 or 5 on the Suicidal Ideation section of the Columbia-Suicide Severity Rating Scale (C-SSRS) in subjects aged 6 and above or based on the opinion of the Investigator for subject less than 6 years.\n- Are scheduled or confirmed or both to have epilepsy surgery within 6 months after Visit 1; however, those who have previously documented “failed” epilepsy surgery will be allowed.\n- Evidence of clinically significant disease (eg, cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the investigator could affect the subject’s safety or interfere with the study assessments.\n- Evidence of moderate or severe renal insufficiency as defined by estimated glomerular filtration rates (eGFRs) based on Bedside Schwartz equation [eGFR=0.413×Height (cm)/Serum Creatinine (mg/dL)] of 31 to less than 60 mL/min/1.73m2 and less than 30 mL/min/1.73m2, respectively. (revised per Amendment 01)"}

Primary endpoints

• {"endpoint_text":"- Proportion of 50% responders for all seizures during the Maintenance Period of Core Study.","definition_or_measurement_approach":"Measured as the 50% responder rate: percent of subjects with at least 50% reduction in their seizure frequency per 28 days compared to baseline (as described in the main objective)."}

Secondary endpoints

• {"endpoint_text":"- Proportion of 50% responders for all seizures during Treatment Period of Core Study and Extension A (revised per Amendment 02).","definition_or_measurement_approach":"Proportion of subjects meeting ≥50% reduction in seizure frequency during the Treatment Period and Extension A."}
• {"endpoint_text":"- Proportion of 25% and 75% responders for all seizures during Maintenance Period of Core Study and during Treatment Period of Core Study and Extension A","definition_or_measurement_approach":"Proportion of subjects meeting ≥25% and ≥75% reduction in seizure frequency during the specified periods."}
• {"endpoint_text":"- Proportion of subjects who are seizure-free during the Maintenance Period of Core Study and during the Treatment Period of Core Study and Extension A","definition_or_measurement_approach":"Proportion of subjects with no seizures during the specified periods."}
• {"endpoint_text":"- Absolute and percent change from baseline in seizure frequency for all seizures during the Treatment Period of Core Study and during the Treatment Period of Core Study and Extension A","definition_or_measurement_approach":"Absolute and percentage change from baseline seizure frequency (per 28 days) during the Treatment Period and Extension A."}
• {"endpoint_text":"- CGIC (Investigator Based) at the end of the Treatment Period of Core Study and at the end of Extension A","definition_or_measurement_approach":"Clinical Global Impression of Change (investigator-rated) assessed at end of Treatment Period and Extension A."}
• {"endpoint_text":"- SGIC (Subject Based) at the end of the Treatment Period of Core Study and at the end of Extension A","definition_or_measurement_approach":"Subject Global Impression of Change (subject-rated) assessed at end of Treatment Period and Extension A."}
• {"endpoint_text":"- Change from baseline in CDR parameters at the end of the Treatment Period of Core Study and at the end of Extension A (revised per Amendment 02)","definition_or_measurement_approach":"Change from baseline in CDR (Cognitive Drug Research?) parameters measured at specified timepoints (revised per Amendment 02)."}
• {"endpoint_text":"- Change from baseline in CBCL parameters at the end of the Treatment Period of Core Study and at the end of Extension A (revised per Amendment 02)","definition_or_measurement_approach":"Change from baseline in CBCL (Child Behavior Checklist) parameters measured at specified timepoints (revised per Amendment 02)."}
• {"endpoint_text":"- Change from baseline in LGPT parameters at the end of the Treatment Period of Core Study and at the end of Extension A (revised per Amendment 02)","definition_or_measurement_approach":"Change from baseline in LGPT parameters measured at specified timepoints (revised per Amendment 02)."}
• {"endpoint_text":"- Changes from baseline in growth and development parameters (height, weight, thyroid, IGF-1, and sexual maturation assessed by Tanner Staging) during Treatment Period of Core Study and Extension A (revised per Amendment 02)","definition_or_measurement_approach":"Change from baseline in anthropometric and laboratory measures and Tanner staging during treatment and extension."}
• {"endpoint_text":"- Proportion of subjects with any treatment-emergent reports of suicidal ideation and behavior on the C-SSRS and intensity of these behaviors assessed using C-SSRS scores during Treatment Period of Core Study, Extension A, and Extension B (revised per Amendment 02)","definition_or_measurement_approach":"Incidence and intensity of suicidal ideation/behavior per Columbia-Suicide Severity Rating Scale (C-SSRS) during treatment and extensions."}
• {"endpoint_text":"- Change from baseline in number of seizures recorded on EEG at the end of the Treatment Period of Core Study and at the end of Extension A","definition_or_measurement_approach":"Change in EEG-recorded seizure counts from baseline to end of Treatment Period and Extension A."}
• {"endpoint_text":"- Safety and tolerability, which include incidence of TEAEs and serious AEs (SAEs), laboratory parameters, vital signs, and ECG parameters during Treatment Period of Core Study, Extension A, and Extension B (revised per Amendment 02)","definition_or_measurement_approach":"Assessment of safety via incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), labs, vitals, and ECG parameters during study periods."}
• {"endpoint_text":"- Characterize the pharmacokinetics (PK) of perampanel and to explore relationships between exposure and safety endpoints, including most common treatment-emergent adverse events (TEAEs), cognition, and behavior","definition_or_measurement_approach":"PK characterization and exposure–response exploratory analyses relating perampanel exposure to safety and clinical endpoints."}

Belgium

Earliest CTIS Part Ii Submission Date

10-04-2024

Latest Decision Or Authorization Date

06-05-2024

Processing Time Days

26

Number Of Sites

2

Number Of Participants

9

France

Earliest CTIS Part Ii Submission Date

10-04-2024

Latest Decision Or Authorization Date

12-06-2024

Processing Time Days

63

Number Of Sites

4

Number Of Participants

15

Germany

Earliest CTIS Part Ii Submission Date

10-04-2024

Latest Decision Or Authorization Date

10-05-2024

Processing Time Days

30

Number Of Sites

2

Number Of Participants

10

Spain

Earliest CTIS Part Ii Submission Date

10-04-2024

Latest Decision Or Authorization Date

06-05-2024

Processing Time Days

26

Number Of Sites

5

Number Of Participants

20

Primary sponsor

Full Name

Eisai Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

PPD Development LP

Responsibilities

Sponsor duties codes: 1, 12, 2 (no descriptive values provided in record).

Name

PPD International Holdings LLC

Responsibilities

Routine clinical pathology testing, Clinical chemistry, Clinical haematology, Clinical microbiology and Sample management of specified samples to referral labs and kitting for the study

Name

IQVIA Limited

Responsibilities

IVRS30 – treatment randomisation.

Name

Signant Health Global LLC

Responsibilities

Sponsor duties code: 7 (no descriptive value provided in record).

Name

Frontage Laboratories Inc.

Responsibilities

PK sample analysis

Name

Oracle

Responsibilities

Sponsor duties code: 7 (no descriptive value provided in record).

Name

Eresearchtechnology Inc.

Responsibilities

ECG analysis/ review and EEG analysis/ review

Third parties

• {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"Patient travel reimburesement.","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"Sponsor duties codes: 1, 12, 2 (no descriptive values provided in record).","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"PPD International Holdings LLC","duties_or_roles":"Routine clinical pathology testing, Clinical chemistry, Clinical haematology, Clinical microbiology and Sample management of specified samples to referral labs and kitting for the study","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"Sponsor duties code: 7 (no descriptive value provided in record).","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Frontage Laboratories Inc.","duties_or_roles":"PK sample analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Oracle","duties_or_roles":"Sponsor duties code: 7 (no descriptive value provided in record).","organisation_type":"Industry"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"ECG analysis/ review and EEG analysis/ review","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"IVRS30 – treatment randomisation.","organisation_type":"Pharmaceutical company"}