Clinical Trials

Inclusion Criteria:

• Subject is male or non-pregnant, non-lactating female, age 2 to 35 years, inclusive as of the day of the Screening Visit. Female subjects of childbearing potential must not be pregnant or breast-feeding. Female subjects of childbearing potential must have a negative urine or serum pregnancy test at screening. Subjects of childbearing or child-fathering potential must be willing to use medically acceptable forms of birth control which includes abstinence, while being treated on this study and for 90 days after the last dose of study drug.
• Subject must have a diagnosis of Lennox-Gastaut syndrome, where seizures that result in drops are not completely controlled by current antiepileptic treatments. (Subjects without a formal diagnosis may still be enrolled after review and consultation between the Investigator and Sponsor, and in some cases, the Epilepsy Study Consortium. Final decisions on enrollment are at the discretion of the sponsor if all other criteria are met.).
• Subjects must meet all of the following 4 criteria for Lennox-Gastaut syndrome, as defined in this protocol:
  • Onset of seizures at 11 years of age or younger;
  • Multiple seizure types (must include TS or TA), including countable motor seizures that result in drops. Countable motor seizure types eligible for inclusion are: GTC, TS, CS, AS, FS with observable motor symptoms, and MS with a drop;
  • Abnormal cognitive development;
  • Evidence of EEG in the medical history that shows abnormal background activity accompanied by slow spike and wave pattern < 2.5 Hz. (Acceptable evidence includes a copy of the EEG trace, EEG report, or physician note that appropriately describes the EEG findings.).
• Subject must have had at least 8 drop seizures in the last 4 weeks prior to Screening (minimum of 4 drop seizures in the first two weeks and 4 in the last two weeks before Screening), by parent/guardian report to Investigator or investigator medical notes.
• Receiving at least 1 concomitant AED and up to 4 concomitant AEDs, inclusive. KD and VNS are permitted but do not count towards the total number of AEDs. Rescue medications for seizures are not counted towards the total number of AEDs.
• All medications or interventions for epilepsy (including KD and VNS) must be stable for at least 4 weeks prior to screening and are expected to remain stable throughout the study.
• Subject has been informed of the nature of the study and informed consent has been obtained from the legally responsible parent/guardian. 
• Subject has provided assent in accordance with Institutional Review Board (IRB)/Ethics Committee requirements, if capable.
• Subject’s parent/caregiver is willing and able to be compliant with diary completion, visit schedule and study drug accountability.

Exclusion Criteria:

• Subject has a known hypersensitivity to fenfluramine or any of the excipients in the study medication.
• Subject’s etiology of seizures is a degenerative neurological disease.
• Subject has a history of hemiclonic seizures in the first year of life.
• Subject only has drop seizures in clusters, where individual seizures cannot be counted reliably.
• Subject has pulmonary arterial hypertension.
• Subject has current or past history of cardiovascular or cerebrovascular disease, such as cardiac valvulopathy, myocardial infarction or stroke, or clinically significant structural cardiac abnormality, including but not limited to mitral valve prolapse, atrial or ventricular septal defects, patent ductus arteriosus (note: Patent Foramen Ovale or a bicuspid valve are not considered exclusionary).
• Subject has current or recent history of Anorexia Nervosa, bulimia, or depression within the prior year that required medical treatment or psychological treatment for a duration greater than 1 month.
• ubject has a current or past history of glaucoma.
• Subject has had an anoxic episode requiring resuscitation within 6 months of the Screening Visit.
• Subject has moderate or severe hepatic impairment. Asymptomatic subjects with mild hepatic impairment (elevated liver enzymes < 3 x ULN and/or elevated bilirubin < 2 x ULN) may be entered into the study after review and approval by the Medical Monitor in conjunction with the Sponsor, in consideration of comorbidities and concomitant medications. 
• Subject has severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73m^2 ).
• Subject is receiving concomitant therapy with any of the following: centrally-acting anorectic agents; monoamine-oxidase inhibitors; any centrally-acting compound with clinically appreciable amount of serotonin agonist or antagonist properties, including serotonin reuptake inhibition; other centrally-acting noradrenergic agonists, including atomoxetine; or cyproheptadine.
  • Note: Short-term medication requirements for prohibited medications will be handled on a per case basis by the Medical Monitor.
• Subject has positive result on urine or serum tetrahydrocannabinol (THC) Panel or whole blood cannabidiol (CBD) at the Screening Visit.
• Subject is taking felbamate for less than 1 year prior to screening and/or does not have stable liver function and hematology laboratory tests, and/or the dose has not been stable for at least 60 days prior to the Screening Visit.
• Subject is known to be human immunodeficiency virus (HIV) positive.
• Subject is known to have active viral hepatitis (B or C).
• Subject is currently receiving an investigational product.
• Subject has participated in another clinical trial within the past 30 days (calculated from that study’s last scheduled visit). Participation in nontreatment trials will be reviewed by the medical monitor.
• Subject is at imminent risk of self-harm or harm to others, in the Investigator’s opinion, based on clinical interview and responses provided on the Columbia-Suicide Severity Rating Scale (C-SSRS). Subjects must be excluded if they report suicidal behavior in the past 6 months as measured by the C-SSRS at Screening or Baseline, which includes suicidal ideation with intent and plan (Item #5). If a subject reports suicidal ideation on Item 4 without specific plan, and the Investigator feels that the subject is appropriate for the study considering the potential risks, the Investigator must document appropriateness for inclusion, and discuss with the parent/caregiver to be alert to mood or behavioral changes, especially around times of dose adjustment.
• Subject is unwilling or unable to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
• Subject is institutionalized in a general nursing home (ie, in a facility that does not provide skilled epilepsy care).
• Subject does not have a reliable caregiver who can provide seizure diary information throughout the study.
• Subject has a clinically significant condition, including chronic obstructive pulmonary disease, interstitial lung disease, or portal hypertension, or has had clinically relevant symptoms or a clinically significant illness in the 4 weeks prior to the Screening Visit, other than epilepsy, that would negatively impact study participation, collection of study data, or pose a risk to the subject.