LIGHTHOUSE · EPX-100-003

Public study eligibility criteria

Inclusion

• Males or females, ages ≥2 to ≤55 years, at the time of Screening.
• Participant, parent, caregiver, or LAR is able and willing to maintain an accurate and complete daily seizure diary.
• Willingness and ability to take study drug (suspension) as directed.
• Sexually active WCBP must be using a medically acceptable method of birth control and have a negative serum or urine pregnancy test at Screening (Visit 1) and at Randomization (Visit 2). A WCBP is defined as a female who is biologically capable of becoming pregnant. Medically acceptable methods of birth control are listed in Appendix 11. In participants who are not sexually active, abstinence is an acceptable form of birth control and pregnancy testing will be conducted per protocol. Women who are of nonchildbearing potential (i.e., postmenopause or surgical menopause) must have this condition captured in their medical history. Pregnant women are excluded from this study.
• Ketogenic diet, or a modified version of this diet, is allowed as long as the diet has been initiated and maintained at a steady state for at least 4 weeks prior to Screening and remains stable throughout the double-blind phase. Changes in ketogenic diet during the DB Period may occasionally be permissible in order to maintain ketosis while receiving study drug. Any changes to the diet during the DB Period will have to be confirmed with the Medical Monitor. Ketogenic diet does not count as an antiseizure medication. During the OLE phase, once therapeutic doses have been fully established (Visit 16 onwards), diet can be changed if deemed necessary by the PI. The Medical Monitor should be notified of any such change (Section 5.3.2).
• Participant/parent/LAR willing and able to give written informed consent/assent, after being properly informed of the nature and risks of the study and prior to engaging in any study-related procedures. If the participant is not qualified or able to provide written informed consent based on age, developmental stage, intellectual capacity, or other factors, parent/LAR must provide appropriate consent for study participation.
• Diagnosis of LGS, including: • Evidence of at least one type of countable major motor seizure. • History of EEG consistent with LGS (abnormal background activity and one of the following (1) slow spike-wave discharges [450 msec (QTcF = QT/3√ RR) at Screening based on the mean of triplicate 12-lead ECGs.
• Has a known history of long QT syndrome or any significant history of a serious abnormality of the ECG (e.g., recent myocardial infarction, clinically significant arrhythmia).
• Has a family history of sudden cardiac death, unexplained death, or death from a primary dysrhythmia potentially associated with QT prolongation in any family member.
• Seizures secondary to illicit drug or alcohol use, infection, neoplasm, demyelinating disease, degenerative neurological disease, or progressive CNS disease, metabolic illness, recent anoxic episode within the last 6 months requiring resuscitation, or progressive degenerative disease or any other condition, which in the opinion of the investigator, could affect seizure control.
• Changes in any chronic medications within the 30 days prior to Screening. All chronic concomitant medications must be stable in dose for at least 30 days prior to the Screening Visit. Minor dose adjustments for tolerability may be permitted after discussion with the Medical Monitor.
• Epilepsy surgery planned during the study or epilepsy surgery within 6 months prior to Screening.
• Concomitant use of drugs that are moderate or strong inhibitors of CYP3A4 or strong and moderate CYP3A4 inducers is prohibited (Note: CYP3A4 inducers, phenobarbital and cenobamate up to 200 mg/day are allowed). Additionally, concomitant use of drugs with a narrow therapeutic index that are sensitive substrates for CYP2C19, CYP2D6, and CYP2C8 is prohibited.
• Concomitant use of lorcaserin. Note: Prior use of lorcaserin is permitted if at least 30 days have passed since the last dose.
• Concomitant use of any prohibited drug listed in Protocol Appendix 1
• Concomitant 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) cardiac valvular heart disease and/or drug-related pulmonary arterial hypertension as indicated by any of the following: • Mild or greater aortic regurgitation or moderate or greater mitral regurgitation. • 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 >35 mmHg.
• A positive result on drug screen for THC at Visit 1 (Screening).
• Concomitant use of THC/non-prescription cannabidiol preparations.
• Does not agree to refraining from intake of grapefruits or grapefruit juice or Seville oranges.
• 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.
• Based on the judgment of the investigator, is unsuitable for the study for any reason, including but not limited to unstable or uncontrolled medical conditions (including psychiatric and neurological conditions) or a medical condition that might interfere with the conduct of the study, confound interpretation of study results, pose a health risk to the participant or compromise the integrity of the study.
• Has a significant risk of committing suicide based on history, routine psychiatric examination, investigator’s judgment, or answering “yes” to Question 4 or 5 on the C‑SSRS (over the past 3 months prior to the first dose) or with any suicidal behavior (i.e., answering “yes” to the suicidal behavior questions) in the last 6 months before Screening.
• Has moderate or severe hepatic impairment. Asymptomatic participants with mild hepatic impairment (elevated liver enzymes [AST or ALT] <3× ULN or elevated bilirubin <2× ULN) may be entered into the study after consideration of comorbidities and concomitant medications.