Clincosm LogoSign in Get a demo

PACIFIC: Study to Investigate LP352 in Subjects With Developmental and Epileptic Encephalopathies

Sponsor
Longboard Pharmaceuticals (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05364021
Collaborator
(none)
50
Enrollment
28
Locations
2
Arms
19
Anticipated Duration (Months)
1.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
50 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Randomized, Double-blind, Placebo-controlled, Parallel-group, Dose-escalation Study to Investigate the Safety, Tolerability, PK, PD, and Exploratory Efficacy of LP352 in Subjects With Developmental and Epileptic Encephalopathies
Actual Study Start Date :
Mar 3, 2022
Anticipated Primary Completion Date :
Oct 1, 2023
Anticipated Study Completion Date :
Oct 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: LP352

Subjects 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.

Drug: LP352
LP352 administered three times daily, orally or through G-tube
Placebo Comparator: Placebo

Placebo for LP352

Drug: Placebo
Matching placebo for LP352 administered three times daily, orally or through G-tube
Other Names:
  • Placebo Comparator

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Treatment-emergent Adverse Events [Baseline 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

    2. Columbia-Suicide Severity Rating Scale (C-SSRS) Response [Baseline up to Day 75]

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

    3. Patient Health Questionnaire-9 Total Score and Question 9 Score [Baseline up to Day 75]

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

    4. Percent Change from Baseline in Observed Countable Motor Seizure Frequency (per 28 Days) During the Treatment Period [Baseline up to Day 75]

    5. Percent Change from Baseline in Observed Countable Motor Seizure Frequency (per 28 Days) During the Maintenance Period [Baseline up to Day 75]

    Secondary Outcome Measures

    1. Observed Plasma Concentrations of LP352 by Time and Dose [Baseline up to Day 75]

    2. Modeled Estimate of Average Plasma Concentration [Baseline up to Day 75]

    3. Modeled Estimate of Observed Plasma Concentration Just Prior to Dosing [Baseline up to Day 75]

    4. Correlation of Plasma Concentration with Incidence of Treatment-emergent Adverse Events [Baseline up to Day 75]

    5. Correlation of Plasma Concentration with Seizure Frequency [Baseline up to Day 75]

    6. Observed and Change from Baseline Prolactin Concentration During the Treatment Period [Baseline up to Day 75]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Arkansas Children's Hospital Little Rock Arkansas United States 72202
    2 Rancho Los Amigos National Rehabilitation Center (RLANRC) Downey California United States 90242
    3 Children's Hospital of Orange County Orange California United States 92868
    4 University of California San Francisco San Francisco California United States 94158
    5 Northwest Florida Clinical Research Group Gulf Breeze Florida United States 32561
    6 University of Miami Miami Florida United States 33136
    7 Advent Health Orlando Orlando Florida United States 32803
    8 Research Institute of Orlando Orlando Florida United States 32806
    9 University of South Florida Tampa Florida United States 33606
    10 Pediatric Neurology PA Winter Park Florida United States 32789
    11 Hawaii Pacific Neuroscience Honolulu Hawaii United States 96817
    12 Northwestern University Feinberg School of Medicine Chicago Illinois United States 60611
    13 Mid-Atlantic Epilepsy and Sleep Center Bethesda Maryland United States 20817
    14 Spectrum Health Grand Rapids Michigan United States 49503
    15 Mayo Clinic Rochester Minnesota United States 55905
    16 Washington University School of Medicine Saint Louis Missouri United States 63110
    17 Boston Children's Health Physicians LLP Hawthorne New York United States 10532
    18 New York University Langone Hospital - Long Island Mineola New York United States 11501
    19 Northwell Health New York New York United States 10075
    20 Northeast Regional Epilepsy Group Staten Island New York United States 10305
    21 OnSite Clinical Solutions LLC Charlotte North Carolina United States 98277
    22 Wake Forest University School of Medicine Winston-Salem North Carolina United States 27157
    23 University Hospitals Cleveland Medical Center Cleveland Ohio United States 44106
    24 Providence Neurological Specialties-East Portland Oregon United States 97213
    25 Oregon Health Sciences University Portland Oregon United States 97239
    26 Austin Epilepsy Care Center Austin Texas United States 78758
    27 University of Utah Salt Lake City Utah United States 84132
    28 University of Washington Valley Medical Center Renton Washington United States 98055

    Sponsors and Collaborators

    • Longboard Pharmaceuticals

    Investigators

    • Principal Investigator: Dennis J Dlugos, MD, Children's Hospital of Philadelphia

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Longboard Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT05364021
    Other Study ID Numbers:
    • LP352-201
    First Posted:
    May 6, 2022
    Last Update Posted:
    Aug 2, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Longboard Pharmaceuticals
    CDKL5 deficiency disorder
    developmental and epileptic encephalopathy
    Dravet Syndrome
    epilepsy
    Lennox-Gastaut Syndrome
    treatment resistant epilepsy
    tuberous sclerosis complex
    Additional relevant MeSH terms:
    Brain Diseases
    Epilepsy
    Epilepsies, Myoclonic
    Lennox Gastaut Syndrome
    Syndrome

    Study Results

    No Results Posted as of Aug 2, 2022