Health Condition 1: G408- Other epilepsy and recurrent seizures
Conditions
Interventions
Intervention1: EPX-100 (Clemizole Hydrochloride): EPX-100 will be administered as an oral solution (5 mg/mL). Taste and color-matching placebo
will be administered as an oral solution. Study drug wil
Sponsors
Epygenix Therapeutics, Inc
Epygenix Therapeutics Inc
Eligibility
Inclusion criteria
Inclusion criteria: Male and female participants 2 years and older at time of consent. 2. Participant or parent/Legally Authorized Representative (LAR) willing and able to provide written informed consent, assent (if applicable) prior to initiation of any study related procedures. 3. Clinical diagnosis of Dravet Syndrome. Participants must have seizures which are not completely controlled by AEDs with the following criteria: • Onset of seizures prior to 18 months of age, • Normal development at onset, • History of seizures that are generalized, unilateral clonic, and/or hemiclonic, • Brain MRI without cortical malformation (not including mild atrophy associated with the natural progression of Dravet Syndrome), and • Genetic mutation of the SCN1A gene must be documented. 4. The participant must be approved to participate by the Independent Reviewer, in collaboration with the PI. Participants will be approved for participation following review of the participantâ??s medical and seizure history, historical neuroimaging, historical EEGs, genetic report confirming SCN1A mutation, and review and classification of at least 28 days of baseline seizures. 5. >=4 countable convulsive seizures within minimum 28-day screening/baseline period (e.g., hemiclonic, secondarily generalized tonic-clonic, generalized tonic-clonic, tonic, clonic, tonic/atonic (resulting in a drop), or focal with clear observable motor signs). 6. Participants should be on a stable regimen of AEDs >=30 days prior to Visit 1 and generally in good health. 7. Participant or parent/ LAR is able and willing to maintain an accurate and complete daily seizure and medication diary for the duration of the trial. 8. Sexually active women of child-bearing potential (WCBP) must be using a medically acceptable method of birth control and have a negative serum or urine pregnancy test at the screening (Visit 1) and Randomization (Visit 2). 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 nonchild-bearing potential, i.e., post-menopause, must have this condition captured in their medical history. Pregnant women are excluded from this study
Exclusion criteria
Exclusion criteria: Known sensitivity, allergy, or previous exposure to EPX-100 (Clemizole HCl). 2. Exposure to any investigational drug or device 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 CNS disease deemed progressive, metabolic illness, 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, and/or phenytoin, as well as refraining from grapefruits and grapefruit juice during the study period. A list of CYP3A4/5/7 inhibitors and inducers is included in Appendix 1. 5. Prior or concurrent use of or lorcaserin. 6. Concurrent use of fenfluramine. Participants with prior use of fenfluramine within the previous 3 months, or without proper documentation of an echocardiogram, at minimum 3 months following the last dose of fenfluramine, to ensure that the participant does not meet any criteria for drug-related (fenfluramine) valvular heart disease and/or drug-related pulmonary arterial hypertension (PAH) as indicated by any of the following: • documented mild or greater aortic regurgitation [AR] or moderate or greater mitral regurgitation [MR] • significant (greater than mild) tricuspid regurgitation • abnormally thickened cardiac valve and/or has restricted motion of the valve leaflets • elevated right heart/pulmonary artery pressure >35mmHg 7. Has any medical condition that, in the PIâ??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, and history of arrhythmias), renal, pulmonary, gastrointestinal, hematologic or hepatic conditions; or a condition that affects the absorption, distribution, metabolism, or excretion of drugs. 8. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the efficacy of EPX-100 compared with placebo as adjunctive therapy in children and adult participants with Dravet Syndrome, in terms of the mean percent change in countable convulsive seizure frequency (CCSF1 ) in the Titration and Maintenance T plus M periods relative to baselineTimepoint: The following assessment will be performed for the evaluation of the secondary efficacy endpoints, also described in Section 4: - Clinical Global Impression: Clinician (CGI-C). - Clinical Global Impression: Participant/Caregiver (CGI-P; Appendix 3; Busner and Targum, 2007). - Quality of Life in Childhood Epilepsy (QOLCE-55; Appendix 4; Conway et al., 2017, Goodwin et al., 2015). - Seizure Severity using Hague Seizure Severity Scale (HASS). Sleep Disturbance | — |
Secondary
| Measure | Time frame |
|---|---|
| To describe the difference between EPX 100 vs placebo in the number of countable convulsive seizure free days in the T plus M periods relative to baselineTimepoint: The number of countable convulsive seizure free days in the T plus M period relative to baseline | — |
Countries
Bulgaria, Canada, Georgia, Hungary, India, Poland, Romania, Spain, United Kingdom, United States of America
Contacts
Public ContactUmakanta Sahoo
GCT Pharma Research (India) Pvt Ltd
Outcome results
None listed