| Eligibility |
Inclusion Criteria:
1. Male or female participants ages 14 years and older at the time of consent.
2. Participant must have a documented history of Lennox-Gastaut Syndrome, including:
- Evidence of at least one type of generalized seizure (see below)
- Electroencephalogram (EEG) diagnostic criteria (abnormal background activity,
slow spike-wave discharges (< 2.5 Hz), and/or paroxysmal fast activity during
sleep), and
- Abnormal cognitive development.
3. Participants must have seizures not completely controlled by ASMs with the following
criteria:
- Onset of seizures at 11 years of age or younger
- History of multiple seizure types that must include tonic or tonic/atonic
seizures as well as current countable seizures that result in fall/drop.
Countable motor seizure types resulting in a drop that are eligible for inclusion
are:
- Focal with clear, observable motor signs (i.e., automatisms, dystonic posturing,
focal tonic stiffening)
- Secondarily generalized tonic clonic (evolving to bilateral convulsive seizure
from focal seizure)
- Generalized tonic clonic convulsion
- Clonic (note bilateral: symmetric R and L), and/or
- Tonic/Atonic.
4. All medication and/or interventions for epilepsy including ketogenic diet and vagus
nerve stimulation (VNS) must have been stable for = 30 days prior to screening and the
participant is willing to maintain a stable regimen throughout the study. Note: The
ketogenic diet and VNS treatments are not counted as an ASM throughout the study.
5. The participant must be approved to participate by the PI after review of the medical
history, baseline seizure calendars, and inclusion/exclusion criteria. The Independent
Reviewer will confirm Lennox-Gastaut Syndrome diagnosis for each participant enrolled
in the study.
6. Seizure criteria of = 4 countable seizures that result in a fall/drop (tonic-clonic,
tonic, clonic, atonic, focal with observable motor signs) per 4-week Baseline period
(Observation Phase).
7. Participants should be on a stable regimen of ASMs = 30 days prior to Visit 1 and
generally in good health.
8. Participant, parent, or LAR is able and willing to maintain an accurate and complete
daily seizure calendar.
9. Sexually active women of child-bearing potential (WCBP) must be using a medically
acceptable method of birth control and have a negative urine pregnancy test at the
screening visit. A WCBP is defined as a female who is biologically capable of becoming
pregnant. A medically acceptable method of birth control includes intrauterine devices
in place for at least 3 months, surgical sterilization, or adequate barrier methods
(e.g., diaphragm and foam). Use of oral contraceptives in combination with another
method (e.g., a spermicidal cream) is acceptable. In participants who are not sexually
active, abstinence is an acceptable form of birth control and urine will be tested per
protocol. Women who are of non-child-bearing potential, i.e., post-menopause, must
have this condition captured in their medical history. Pregnant women are excluded
from this study.
10. Have participant, parent, or LAR available and willing to give written informed
consent, after being properly informed of the nature and risks of the study and prior
to engaging in any study-related procedures.
Exclusion Criteria:
1. Known sensitivity, allergy, or previous exposure to EPX-100 (clemizole HCl).
2. Exposure to any investigational drug or device = 90 days prior to screening or plans
to participate in another drug or device trial at any time during the study.
3. Seizures secondary to illicit drug or alcohol use, infection, neoplasm, demyelinating
disease, degenerative neurological disease, or progressive central nervous system
(CNS) disease, metabolic illness, recent anoxic episode within the last 6 months
requiring resuscitation, or progressive degenerative disease.
4. Concurrent use of drugs known to interfere with EPX-100, including moderate or severe
inducers or inhibitors of CYP3A4/5/7. Specifically, concurrent use of carbamazepine,
oxcarbazepine, phenytoin, gabapentin, phenobarbital, and/or fenfluramine are excluded.
Subjects who are unable to agree to refraining from grapefruits and grapefruit juice
during the study period. Refer to Appendix 1 for a list of prohibited drugs.
5. Receiving concomitant therapy with: centrally-acting anorectic agents; monoamine
oxidase (MAO) inhibitors; any centrally-acting drugs with clinically appreciable
amounts of serotonin agonist or antagonist properties, including serotonin reuptake
inhibition (SRIs, SSRIs). Also, systemic corticosteroids (inhaled steroids are
allowed) and intravenous immunoglobulin (IVIG) may reduce seizure frequency, thus are
excluded throughout the study.
6. Has any medical condition that, in the PI's judgment, is considered to be clinically
significant and could potentially affect participant safety or study outcome,
including but not limited to: clinically significant cardiac disease (including
angina, congestive heart failure, uncontrolled hypertension, history of arrhythmias,
and/or clinical valvulopathy), renal, pulmonary, gastrointestinal, hematologic or
hepatic conditions; or a condition that affects the absorption, distribution,
metabolism, or excretion of drugs.
7. Has an active suicidal plan/intent or have had active suicidal thoughts in the past 6
months or a suicide attempt in the past 3 years.
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