A Study of a Drug to be Used in Addition With Another Drug to Treat Adults With Uncontrolled Partial-onset Seizures

A study of a drug to be used in addition with another drug to treat adults with Uncontrolled
Partial-onset Seizures

Eligibility Criteria

Inclusion Criteria:

1. Male or female subjects ≥ 18 years of age.

2. Subject is willing and able to sign informed consent.

3. Subject has a documented diagnosis of epilepsy with simple POS with a motor component
or complex POS with or without secondarily generalized seizures as defined in the
Classification of Seizures of the International League Against Epilepsy

4. Subject has a documented electroencephalogram within 10 years prior to screening.

5. Subject has had at least 3 POS during previous six months.

6. Subject has had a sufficient number of seizures at time of enrollment to justify
adjunctive therapy, as determined by the Investigator.

7. Subjects are required to be ESL-naïve AND

1. Maintained on a stable LEV or LTG regimen for at least 1 month (28 days) prior to
screening with no history of adjunctive treatment (for Arm 1, ESL as first
add-on).

OR

2. Maintained on a stable dose of 1-2 AEDs (excluding OXC) for at least 1 month (28
days) prior to screening and who have had prior adjunctive treatment (for Arm 2,
ESL as later add-on).

8. If the subject is treated with any stimulation device for epilepsy Vagal Nerve
Stimulation (VNS), Responsive Neurostimulator (RNS), or similar, the device must have
been implanted at least 6 months before screening and the device parameters must be
documented as stable for at least 1 month prior to screening. (Note: These devices
will not be counted as concomitant AED).

9. Except for epilepsy, subject is judged to be in general good health based on medical
history, physical examination findings, and clinical laboratory

Exclusion Criteria:

1. Subjects with a prior exposure to ESL.

2. Subjects currently being treated with OXC.

3. Subject with a history of allergic reaction to OXC or CBZ, or a history of serious
allergic reaction (Stevens-Johnson syndrome, Drug Reaction with Eosinophilia and
Systemic Symptoms or similar) to any AED, or a history of serious allergic reactions
to other medications.

4. Subjects who have taken warfarin, felbamate, vigabatrin, or perampanel, (unless at
stable dose with safety testing for ≥ 1 year) within a 4-week period prior to
screening.

5. Subjects taking ezogabine

6. Subject has taken any medication prohibited for this protocol within 4 weeks prior to
Screening

7. Subjects using benzodiazepines on more than an occasional basis (defined as more than
2 times per week), except when used chronically as an AED

8. Seizure disorder characterized primarily by simple POS without motor signs.

9. Subject has a history of primarily generalized seizures (eg, myoclonic, absence,
tonic).

10. Subject has a history of status epilepticus or cluster seizures (ie, 3 or more
seizures within 30 minutes) within the 3 months prior to screening.

11. Subject has had seizures of psychogenic origin or purely subjective seizures within
the last 2 years.

12. Subject has had seizures too close to count accurately.

13. Subject has a known progressive structural central nervous system (CNS) lesion,
progressive encephalopathy, or a progressive cerebral abnormality.

14. Subject whose current seizures are related to an acute medical illness or other
non-epileptic origin.

15. Subjects of Asian ancestry will be excluded if they are carriers of HLA-B*1502.
Either:

1. Subject must give written informed consent for genotyping, and test negative. OR

2. Subjects must provide documentation of prior testing confirming non-carrier
status.

16. Subject has a major medical illness other than epilepsy that would prevent safe
participation in this study, at the discretion of the Investigator, including (but not
limited to) cardiac disease, thyroid disease, hepatic or renal impairment, endocrine
or metabolic disease, gastrointestinal disease, or hematologic disease. Note: Active
medical conditions that are minor or well-controlled are not exclusionary if they do
not affect risk to the subject or the study results. If the effect of the condition in
regard to the risk to the subject or to the study results is unclear, the Medical
Monitor should be consulted.

17. Subjects with clinically relevant laboratory abnormalities at screening (eg, sodium <
130 mEq/L, alanine transaminase (ALT) or aspartate transaminase (AST) > 2.0 times the
upper limit of the normal, white blood cell [WBC] count < 3,000 cells/mm3, estimated
creatinine clearance < 50 mL/min, or has values for thyroid testing (free
triiodothyronine (T3), free thyroxine (T4), thyroid stimulating hormone [TSH])
indicating the presence of significant thyroid dysfunction.

18. Subject has a history or presence of abnormal electrocardiogram (ECG), which in the
Investigator's opinion is clinically significant or QT interval corrected for heart
rate using the Fridericia method (QTcF) of ≥ 450 msec per screening ECG.

19. Subject has second or third-degree atrioventricular block that is not corrected with a
pacemaker.

20. Subjects who meet the Diagnostic and Statistical Manual of Mental Disorders, 5th
edition text revision defined criteria for major depressive episode within the last 6
months. Subjects with mild, chronic depression without recent hospitalization who are
being maintained on a stable dose of a single antidepressant are acceptable.

21. Subject has an active suicidal plan or intent (in the Investigator's opinion) in the
past 4 weeks prior to screening.

22. Subject has a history of suicide attempt in the last 2 years prior to screening.

23. Subject has other major psychiatric disorders.

24. Subjects who are not able to complete the diaries in the Investigator's opinion.

25. Subject has a history of alcohol or substance abuse within 2 years prior to screening
for study participation, or subjects currently using alcohol, drugs of abuse, or any
prescribed or over-the-counter medication in a manner, which, in the opinion of the
Investigator, indicates abuse.

26. Subject tests positive for drugs of abuse at screening. Note: Subjects with a positive
drug screen for marijuana, amphetamines, opiates, or benzodiazepines, who have a
documented prescription for a medical condition and are on a stable dose of this
prescribed medication for at least 4 weeks prior to screening, may be eligible to
participate in the study upon approval from the Medical Monitor.

27. Subject is pregnant, currently nursing, or intends to become pregnant during the study
period or within 30 days of the last dose of study drug.

28. Subject has participated in any investigational study within 30 days prior to
screening, as documented in subject's medical history.

29. Subject is a clinical or investigational site staff member or relative of a staff
member.

30. Any other condition or circumstance that, in the opinion of the Investigator, may
compromise the subject's ability to comply with the study protocol.

Principal Investigator

Nancy Hammond, MD

Study Contact

Lindsay Richardson 913-574-0412

Estimated Completion Date

Monday, February 11, 2019

ClinicalTrials.gov #

NCT03116828
02/22/2018