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Study to Investigate LP352 in Subjects With Developmental and Epileptic Encephalopathies

Phase 1
Completed
Conditions
Developmental and Epileptic Encephalopathy
Lennox Gastaut Syndrome
Dravet Syndrome
Interventions
Drug: Placebo
Registration Number
NCT05364021
Lead Sponsor
Longboard Pharmaceuticals
Brief Summary

The objective of this study is to assess the safety, tolerability, efficacy, and pharmacokinetics of adjunctive therapy of LP352 in adults and adolescents with developmental and epileptic encephalopathies.

Detailed Description

This is a randomized, double-blind, parallel-group, dose-escalation, placebo-controlled study of LP352 in adults and adolescents with developmental and epileptic encephalopathies (DEE) with an average of ≥ 4 observed/countable motor seizures per 4-week period during the 12 weeks before screening while on stable antiseizure medicine (ASM).

Subjects will be randomized 4:1 to LP352 or placebo. The study will have a baseline period of 28 days, followed by a 15 day up-titration period during which time subjects will titrate up to their highest tolerated doses, and a 60-day maintenance period. After Day 75, subjects will be tapered down over a period of up to 15 days, with a follow-up visit 30 days after last dose. Enrolled subjects will be allowed to continue treatment with up to 4 concomitant ASMs at a stable dose.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
52
Inclusion Criteria
  1. Male or non-pregnant, non-lactating female, age 12 to 65 years
  2. Diagnosis of Dravet syndrome, Lennox-Gastaut syndrome, or other developmental and epileptic encephalopathy
  3. Has a minimum number of seizures per 4-week period while taking 1 to 4 anti-seizure medications
  4. All medications and epilepsy interventions must be stable for 4 weeks before screening and are expected to remain stable during the study
  5. The patient/parent/caregiver is able and willing to attend study visits, complete the diary and take study drug as instructed

Key

Exclusion Criteria
  1. Current or past history of cardiovascular or cerebrovascular disease, such as cardiac valvulopathy, myocardial infarction, stroke, pulmonary arterial hypertension or abnormal blood pressure
  2. Has glaucoma, renal impairment, liver disease or any other medical condition that would affect study participation or pose a risk to the subject
  3. Current or recent history of moderate or severe depression, anorexia nervosa, bulimia or at risk of suicidal behavior
  4. Currently taking anorectic agents, monoamine oxidase inhibitors; serotonin agonists or antagonists including fenfluramine, atomoxetine, vortioxetine, or other medications for weight loss
  5. Positive test result on the drug screen, except tetrahydrocannabinol (THC) for patients taking prescribed cannabidiol

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboPlacebo for LP352
LP352LP352Subjects will be titrated up to highest tolerated dose of LP352 during a 15-day period, followed by a 60-day maintenance period and a 15-day taper/down titration period.
Primary Outcome Measures
NameTimeMethod
Columbia-Suicide Severity Rating Scale (C-SSRS) ResponseBaseline up to Day 75

Type of Suicidal Ideation, Intensity (1 - 5, with 5 being most severe), Suicidal Behavior

Percent Change from Baseline in Observed Countable Motor Seizure Frequency (per 28 Days) During the Maintenance PeriodBaseline up to Day 75
Treatment-emergent Adverse EventsBaseline up to Day 75

Incidence and severity of adverse events, including serious adverse events and adverse events leading to study discontinuation and clinically significant changes in vital signs, physical examination endpoints, clinical safety laboratory values and ECGs

Patient Health Questionnaire-9 Total Score and Question 9 ScoreBaseline up to Day 75

Severity Rating Scale: 0 - 27; higher scores indicate greater severity of depressive disorder

Percent Change from Baseline in Observed Countable Motor Seizure Frequency (per 28 Days) During the Treatment PeriodBaseline up to Day 75
Secondary Outcome Measures
NameTimeMethod
Observed Plasma Concentrations of LP352 by Time and DoseBaseline up to Day 75
Modeled Estimate of Average Plasma ConcentrationBaseline up to Day 75
Modeled Estimate of Observed Plasma Concentration Just Prior to DosingBaseline up to Day 75
Correlation of Plasma Concentration with Incidence of Treatment-emergent Adverse EventsBaseline up to Day 75
Correlation of Plasma Concentration with Seizure FrequencyBaseline up to Day 75
Observed and Change from Baseline Prolactin Concentration During the Treatment PeriodBaseline up to Day 75

Trial Locations

Locations (34)

University of Miami

🇺🇸

Miami, Florida, United States

Consultants in Epilepsy and Neurology

🇺🇸

Boise, Idaho, United States

Royal Brisbane Women's Hospital

🇦🇺

Herston, Queensland, Australia

Northwestern University Feinberg School of Medicine

🇺🇸

Chicago, Illinois, United States

Northeast Regional Epilepsy Group

🇺🇸

Staten Island, New York, United States

Northwest Florida Clinical Research Group

🇺🇸

Gulf Breeze, Florida, United States

Mid-Atlantic Epilepsy and Sleep Center

🇺🇸

Bethesda, Maryland, United States

Arkansas Children's Hospital

🇺🇸

Little Rock, Arkansas, United States

Boston Children's Health Physicians LLP

🇺🇸

Hawthorne, New York, United States

Research Institute of Orlando

🇺🇸

Orlando, Florida, United States

University of Arizona - Health Sciences Center

🇺🇸

Tucson, Arizona, United States

Northwell Health

🇺🇸

New York, New York, United States

Hawaii Pacific Neuroscience

🇺🇸

Honolulu, Hawaii, United States

Child Neurology Consultants of Austin

🇺🇸

Austin, Texas, United States

Austin Health

🇦🇺

Heidelberg, Victoria, Australia

Queensland Children's Hospital

🇦🇺

South Brisbane, Queensland, Australia

Washington University School of Medicine

🇺🇸

Saint Louis, Missouri, United States

University of Utah

🇺🇸

Salt Lake City, Utah, United States

Children's Hospital of Orange County

🇺🇸

Orange, California, United States

University of California San Francisco

🇺🇸

San Francisco, California, United States

Austin Epilepsy Care Center

🇺🇸

Austin, Texas, United States

Rancho Los Amigos National Rehabilitation Center (RLANRC)

🇺🇸

Downey, California, United States

Advent Health Orlando

🇺🇸

Orlando, Florida, United States

University of South Florida

🇺🇸

Tampa, Florida, United States

New York University Langone Hospital - Long Island

🇺🇸

Mineola, New York, United States

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

OnSite Clinical Solutions LLC

🇺🇸

Charlotte, North Carolina, United States

Wake Forest University School of Medicine

🇺🇸

Winston-Salem, North Carolina, United States

Providence Neurological Specialties-East

🇺🇸

Portland, Oregon, United States

University of Washington Valley Medical Center

🇺🇸

Renton, Washington, United States

Spectrum Health

🇺🇸

Grand Rapids, Michigan, United States

Alfred Health

🇦🇺

Melbourne, Victoria, Australia

Monash Children's Hospital, Monash Health

🇦🇺

Clayton, Victoria, Australia

University Hospitals Cleveland Medical Center

🇺🇸

Cleveland, Ohio, United States

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