A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Cenobamate Adjunctive Therapy in Subjects with Primary Generalized Tonic-Clonic Seizures

Phase 1

• Conditions: Primary Generalized Tonic-Clonic Seizures; MedDRA version: 20.0 Level: HLT Classification code 10018101 Term: Generalised tonic-clonic seizures System Organ Class: 100000004852; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2018-001337-41-CZ
• Lead Sponsor: SK Life Science, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-10-18
• Last Update Posted: 10 December 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 152

Inclusion Criteria

1. Subject is male or female and aged =18 years.
2. Written informed consent signed by the subject or legal guardian, prior to entering the study, in accordance with the International Council for Harmonisation (ICH) Good Clinical Practice (GCP) guidelines. If the
written informed consent is provided by the legal guardian because the
subject is unable to do so, a written or verbal assent from the subject
must also be obtained. As required by country-specific regulations, only
the subject may sign the ICF in accordance with ICH guidelines.
3. Female subjects of childbearing potential are willing to use an acceptable
form of birth control
4. Subject has a clinical diagnosis of PGTC seizures (with or without other
subtypes of generalized seizures) in the setting of idiopathic generalized
epilepsy.
5. Subject experiences at least 5 PGTC seizures in 12 weeks during the
Pre-Randomization Period.
6. Subject has had a routine electroencephalogram (EEG) within 5 years
prior to Visit 1 (Screening/Baseline) or during the Pre-Randomization
Period with electroencephalographic features consistent with idiopathic
generalized epilepsy; other concomitant anomalies must be explained by
adequate past medical history.
7. Subject has undergone computed tomography (CT) or magnetic
resonance imaging (MRI) within 10 years prior to Visit 1
(Screening/Baseline) or during the Pre-Randomization Period that ruled
out a progressive cause of epilepsy.
8. Subject is currently receiving 1 to a maximum of 3 concomitant
antiepileptic drugs (AEDs) with fixed dosing regimens for a minimum
of 30 days prior to Visit 1 (Screening/Baseline).
a) Benzodiazepines (except diazepam, see Exclusion Criterion No. 7)
taken at least once per week during the 30 days prior to Visit 1
(Screening/Baseline) for epilepsy, anxiety, or sleep disorder will be
counted as 1 AED and the dosage must be continued unchanged
throughout the study. Therefore, only a maximum of 2 additional
approved AEDs will be allowed. (See Exclusion Criterion No. 10
for intermittent benzodiazepine rescue parameters.)
b) Subjects receiving felbamate as a concomitant AED must meet the
following criteria:
i. Have a 2-year history of felbamate use and a history of a fixed
dosing regimen for a minimum of 60 days prior to Visit 1
(Screening/Baseline).
ii. No prior or known history of hepatotoxicity or hematologic
disorder due to felbamate.
9. Subject with an implanted vagal nerve or deep brain stimulator will be
allowed if the stimulator was implanted at least 5 months prior to Visit 1
(Screening/Baseline) and the stimulator parameters are not changed for
30 days prior to Visit 1 and for the duration of the study.
10. Subject taking a ketogenic diet will be allowed as long as the diet has

Exclusion Criteria

1. Female subjects who are pregnant (or planning to become pregnant
during the study), lactating, or breast-feeding.
2. Subject has a history of status epilepticus that required hospitalization
within 12 months prior to Visit 1 (Screening/Baseline).
3. Subject has PGTC seizure clusters where individual seizures cannot be
counted or classified.
4. Subject has a history of non-epileptic psychogenic seizures.
5. Subject has a concomitant diagnosis of partial onset seizure (POS).
6. Subject has a clinical diagnosis of Lennox-Gastaut syndrome.
7. Subject is currently taking (within the 30 days prior to Visit 1
[Screening/Baseline]) any of the following medications: diazepam (for
any reason other than as intermittent benzodiazepine rescue medication),
phenytoin, mephenytoin, fosphenytoin, phenobarbital, primidone,
ethotoin, clopidogrel, fluvoxamine, amitriptyline, clomipramine,
bupropion, methadone, ifosfamide, cyclophosphamide, or efavirenz.
8. Subject has participated in previous cenobamate clinical studies.
9. Subject has a history of vigabatrin use within 5 months prior to Visit 1
(Screening/Baseline), or the subject plans to begin treatment with
vigabatrin during the study.
a) A subject with a history of vigabatrin use that ended more than
5 months prior to Visit 1 may be enrolled after documented evidence
of no vigabatrin-associated clinically significant abnormality in an
automated visual perimetry test.
10. Subject has a history of intermittent use of rescue benzodiazepines (i.e.,
1 to 2 doses over a 24-hour period is considered a 1-time rescue) 4 or
more times within the 30 days prior to Visit 1 (Screening/Baseline).
11. Subject has received an investigational drug or device within 30 days
prior to Visit 1 (Screening/Baseline).
12. Subject has a history of drug or alcohol dependency or abuse within
2 years prior to Visit 1 (Screening/Baseline).
13. Subject tests positive, via urine drug screen at Visit 1
(Screening/Baseline), for illicit drugs (e.g., tetrahydrocannabinol,
amphetamines) or for a drug that has not been prescribed (e.g., certain
opiates).
14. Subject has a history of any serious drug-induced hypersensitivity
reaction (including, but not limited to, Stevens Johnson syndrome, toxic epidermal necrolysis, or Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS]) or any drug-related rash requiring hospitalization.
15. History of AED-associated rash that involved conjunctiva or mucosae.
16. History of more than one non-serious drug-related hypersensitivity
reaction that required discontinuation of the medication.
17. Subject has evidence of clinically significant abnormalities or disease
(e.g., psychiatric, cardiac, respiratory, gastrointestinal, hepatic [AST or
ALT more than 2 times the upper limit of normal (ULN), o

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified