Clinical Trials

Inclusion Criteria:

• Participant is >2 to <65 years of age at the time of Screening with a body weight ≥10 kg.
• Diagnosis of DS must fulfill all of the following criteria:
  • Onset of seizures age >1 and <20 months in an otherwise healthy infant.
  • History of at least 1 of the following seizure type(s):
    • Prolonged generalized tonic-clonic
    • Hemiclonic
    • Myoclonic
    • Tonic
    • Atonic
    • Atypical absence
    • Focal impaired awareness
    • Nonconvulsive status epilepticus
  • Some seizures are induced by prolonged exposure to warm temperatures, fevers due to illness or vaccines, high levels of activity, sudden temperature changes, and/or strong natural/fluorescent lighting or certain visual patterns.
  • Development was normal or only mildly delayed prior to the onset of seizures.
  • Presence of developmental plateauing or regression.
  • In the absence of inclusion criteria 2c and 2e, documented history of SCN1A gene mutation consistent with DS.
  • There is no alternative diagnosis that can be attributed to the participant’s seizure etiology.
• Current occurrence of at least 1 of the following countable motor seizure types:
  • Generalized tonic-clonic
  • Tonic
  • Clonic (hemiclonic or bilateral)
  • Atonic with truncal involvement
  • Focal motor
  • Focal to bilateral tonic-clonic
• Demonstrated an average of at least 4 countable motor seizures (as per inclusion criterion 3) per month for the 3 months prior to Screening, based on the participant/caregiver report and investigator’s assessment.
• Has been taking 1 to 4 ASMs at a stable dose for at least 4 weeks prior to Screening and the participant and/or their caregiver is willing to keep the regimen stable throughout the study.
• G-tube/PEG tube (where present) should have been placed and functioning for at least 3 months prior to Screening. Nasogastric tubes are not allowed except for short-term management after Baseline.
• Has at least one reliable and consistent parent, legal guardian, or caregiver.
• The participant must be willing and able to provide written informed consent; in instances where the participant is unable to provide consent, an appropriate legal representative must provide informed consent and the participant will need to assent (as per local regulations) before participation in the study. If the participant cannot provide assent (ie, due to developmental status), the investigator should document why assent was not obtained.
• The participant and/or authorized representative is willing to provide written consent or assent to allow the investigator and the investigator’s staff to consult with the participant’s medical caregivers and the medical monitor during Screening and during participation in the study.
• All participants of childbearing potential must have a negative serum pregnancy (human chorionic gonadotropin) test at Screening and a negative urine or serum pregnancy test before randomization and agrees to routinely use an adequate method of contraception from the time of signing informed consent throughout the duration of the study and for 30 days after the last dose of study drug. Definitions, acceptable methods of contraception, and reporting responsibilities are defined in Appendix 15.1.
• Participant and/or participant’s caregiver(s) agree to not post any participant’s personal medical data related to the study or information related to the study on any website or social media site until the study has been completed.
• The participant, parent, or caregiver is willing and able (in the judgment of the investigator) to comply with completion of the diaries throughout the study.

Randomization Inclusion Criteria:

• Investigator completion of the Seizure Identification and Diagnostic Review Form (SIF/DRF) and submission to the ESCI for their review and approval before randomization of otherwise eligible participants.
• Approved for study inclusion by ESCI and sponsor.
• Has a stable Baseline with at least 4 countable motor seizures (as per inclusion criteria 3) over 28 consecutive days during Screening.
• The participant, parent, legal guardian, or caregiver has been compliant with diary completion during Screening, in the opinion of the investigator (ie, no more than 5 total days missing).
• The participant, parent, legal guardian, or caregiver responsible for study drug administration demonstrates an understanding of how to administer study drug correctly.

Exclusion Criteria:

• Has a history of infantile/epileptic spasms.
• Has been admitted to a medical facility for treatment of status epilepticus requiring mechanical ventilation within 3 months prior to Screening.
• Has a neurodegenerative disorder as indicated by magnetic resonance imaging or genetic testing.
• Has an acquired lesion/injury unrelated to the primary etiology that could contribute as a secondary cause of seizures.
• Is on a ketogenic or other epilepsy diet (ie, Modified Atkins, low glycemic index) that has been started within 3 months prior to Screening (Visit 1), has been changed within 4 weeks prior to Screening, or is anticipated to change during the study (except for weight-based changes).
• Has had neuromodulation (ie, vagus nerve stimulator, responsive neurostimulator, or deep brain stimulator) implanted within 6 months prior to Screening, settings have been changed within 4 weeks prior to Screening, and/or settings are anticipated to change during the study.
• Has had epilepsy resective surgery (including corpus callosotomy) within 6 months prior to Screening or is anticipated to have epilepsy resective surgery during the study.
• Is anticipated to undergo epilepsy presurgical evaluation in which ASMs will be reduced or temporarily discontinued or requires invasive monitoring during the study.
• Is on one of the following exclusionary medications:
  • Use of fenfluramine or lorcaserin within 28 days prior to Screening, or failed either in the past
  • Sodium channel blockers that increased seizure frequency in the participant (eg, phenytoin, carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, lacosamide, rufinamide) within 28 days prior to Screening
  • Felbamate, unless the participant is on a stable dose of felbamate ≥ 12 months prior to Screening with stable liver function and hematology laboratory tests
  • Topiramate or zonisamide, unless the participant is on a stable dose ≥ 6 months prior to Screening with stable weight
  • MAO inhibitors
• Considered at risk of suicidal behavior based on the C‑SSRS. A participant should be excluded, and a risk assessment should be done by a qualified mental health professional if the participant has had suicidal intent (ideation items 4 or 5) in the last 6 months before randomization, or suicidal behaviors or attempts in the past year. If the participant is unable to complete the C-SSRS due to developmental status, an authorized representative may be used for the completion of the C-SSRS. The investigator may also use clinical judgment, which must then be documented in the source document.
• Patient Health Questionnaire-9 score of >9 or a positive response to Question 9.
• Current or recent history of moderate or severe depression, anorexia nervosa, or bulimia per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, within the prior year.
• Has an abnormal and clinically significant 12-lead ECG at Screening in the opinion of the investigator, for example, second- or third-degree heart block or a QTc of > 450 msec for adult males, > 470 msec for adult females, or > 440 msec for pediatric participants. Entry of any participant with an abnormal but not clinically significant ECG must be approved and documented by signature by appropriately qualified study physician.
• Concomitant use of drugs whose exposures might be altered by LP352, from first dose of study drug until Follow-up.
• Has a history of alcohol, opioid, or other drug use disorder, as per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, within the previous 2 years prior to Screening.
• Use of any cannabis product or cannabidiol that is not in oral solution/capsule/tablet form, not obtained from a government-approved dispensary, or containing ≥ 50% THC. Cannabis product or cannabidiol should be used primarily to treat seizures and dose should not be adjusted within 4 weeks prior to Screening or for the duration of the study. Cannabis product or cannabidiol will count as a concurrent ASM.
• Has a positive result on the urine drug screen, except for positive results related to prescribed controlled medications (eg, benzodiazepine) or Epidiolex/government-approved cannabis product/cannabidiol used to treat seizures (eg, tetrahydrocannabinol).
• Unstable, clinically significant neurologic (other than the disease being studied; eg, recurrent strokes), psychiatric, cardiovascular (eg, pulmonary arterial hypertension, cardiac valvulopathy, orthostatic hypotension/tachycardia) pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, hematopoietic, or endocrine disease or other abnormality which may impact the ability of the participant to participate or potentially confound the study results.
• Is pregnant, breast-feeding, or intending to become pregnant before, during, or within 30 days after participating in this study; or intending to donate ova during such time period.
• Has a known hypersensitivity to any component of LP352 formulation or any history of serious drug-induced hypersensitivity, eg, toxic epidermal necrolysis or Drug Reaction with Eosinophilia and Systemic Symptoms.
• Unwilling to abstain from donation of blood during and within 2 weeks after the study.
• Has been part of a clinical study involving another investigational product in the previous 30 days or within 5 half-lives of the other investigational product prior to Screening, whichever is longer, or participant is currently receiving an investigational product.
• Has previously participated in a clinical study with LP352 (bexicaserin).
• Is unable or unwilling to comply with any of the study requirements or timelines.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 10/25/2024. Questions regarding updates should be directed to the study team contact.