search
Back to results

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

Primary Purpose

Developmental and Epileptic Encephalopathy, Dravet Syndrome, Lennox Gastaut Syndrome

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
LP352
Placebo
Sponsored by
Longboard Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Developmental and Epileptic Encephalopathy focused on measuring CDKL5 deficiency disorder, developmental and epileptic encephalopathy, Dravet Syndrome, epilepsy, Lennox-Gastaut Syndrome, treatment resistant epilepsy, tuberous sclerosis complex

Eligibility Criteria

12 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Arizona - Health Sciences Center
  • Arkansas Children's Hospital
  • Rancho Los Amigos National Rehabilitation Center (RLANRC)
  • Children's Hospital of Orange County
  • University of California San Francisco
  • Northwest Florida Clinical Research Group
  • University of Miami
  • Advent Health Orlando
  • Research Institute of Orlando
  • University of South Florida
  • Hawaii Pacific Neuroscience
  • Consultants in Epilepsy and Neurology
  • Northwestern University Feinberg School of Medicine
  • Mid-Atlantic Epilepsy and Sleep Center
  • Spectrum Health
  • Mayo Clinic
  • Washington University School of Medicine
  • Boston Children's Health Physicians LLP
  • New York University Langone Hospital - Long Island
  • Northwell Health
  • Northeast Regional Epilepsy Group
  • OnSite Clinical Solutions LLC
  • Wake Forest University School of Medicine
  • University Hospitals Cleveland Medical Center
  • Providence Neurological Specialties-East
  • Child Neurology Consultants of Austin
  • Austin Epilepsy Care Center
  • University of Utah
  • University of Washington Valley Medical Center
  • Royal Brisbane Women's Hospital
  • Queensland Children's Hospital
  • Monash Children's Hospital, Monash Health
  • Austin Health
  • Alfred Health

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

LP352

Placebo

Arm Description

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.

Placebo for LP352

Outcomes

Primary Outcome Measures

Treatment-emergent Adverse Events
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
Columbia-Suicide Severity Rating Scale (C-SSRS) Response
Type of Suicidal Ideation, Intensity (1 - 5, with 5 being most severe), Suicidal Behavior
Patient Health Questionnaire-9 Total Score and Question 9 Score
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 Period
Percent Change from Baseline in Observed Countable Motor Seizure Frequency (per 28 Days) During the Maintenance Period

Secondary Outcome Measures

Observed Plasma Concentrations of LP352 by Time and Dose
Modeled Estimate of Average Plasma Concentration
Modeled Estimate of Observed Plasma Concentration Just Prior to Dosing
Correlation of Plasma Concentration with Incidence of Treatment-emergent Adverse Events
Correlation of Plasma Concentration with Seizure Frequency
Observed and Change from Baseline Prolactin Concentration During the Treatment Period

Full Information

First Posted
March 22, 2022
Last Updated
September 18, 2023
Sponsor
Longboard Pharmaceuticals
search

1. Study Identification

Unique Protocol Identification Number
NCT05364021
Brief Title
Study to Investigate LP352 in Subjects With Developmental and Epileptic Encephalopathies
Acronym
PACIFIC
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 3, 2022 (Actual)
Primary Completion Date
October 2023 (Anticipated)
Study Completion Date
October 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Longboard Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Developmental and Epileptic Encephalopathy, Dravet Syndrome, Lennox Gastaut Syndrome
Keywords
CDKL5 deficiency disorder, developmental and epileptic encephalopathy, Dravet Syndrome, epilepsy, Lennox-Gastaut Syndrome, treatment resistant epilepsy, tuberous sclerosis complex

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
LP352
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo for LP352
Intervention Type
Drug
Intervention Name(s)
LP352
Intervention Description
LP352 administered three times daily, orally or through G-tube
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo Comparator
Intervention Description
Matching placebo for LP352 administered three times daily, orally or through G-tube
Primary Outcome Measure Information:
Title
Treatment-emergent Adverse Events
Description
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
Time Frame
Baseline up to Day 75
Title
Columbia-Suicide Severity Rating Scale (C-SSRS) Response
Description
Type of Suicidal Ideation, Intensity (1 - 5, with 5 being most severe), Suicidal Behavior
Time Frame
Baseline up to Day 75
Title
Patient Health Questionnaire-9 Total Score and Question 9 Score
Description
Severity Rating Scale: 0 - 27; higher scores indicate greater severity of depressive disorder
Time Frame
Baseline up to Day 75
Title
Percent Change from Baseline in Observed Countable Motor Seizure Frequency (per 28 Days) During the Treatment Period
Time Frame
Baseline up to Day 75
Title
Percent Change from Baseline in Observed Countable Motor Seizure Frequency (per 28 Days) During the Maintenance Period
Time Frame
Baseline up to Day 75
Secondary Outcome Measure Information:
Title
Observed Plasma Concentrations of LP352 by Time and Dose
Time Frame
Baseline up to Day 75
Title
Modeled Estimate of Average Plasma Concentration
Time Frame
Baseline up to Day 75
Title
Modeled Estimate of Observed Plasma Concentration Just Prior to Dosing
Time Frame
Baseline up to Day 75
Title
Correlation of Plasma Concentration with Incidence of Treatment-emergent Adverse Events
Time Frame
Baseline up to Day 75
Title
Correlation of Plasma Concentration with Seizure Frequency
Time Frame
Baseline up to Day 75
Title
Observed and Change from Baseline Prolactin Concentration During the Treatment Period
Time Frame
Baseline up to Day 75

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Male or non-pregnant, non-lactating female, age 12 to 65 years Diagnosis of Dravet syndrome, Lennox-Gastaut syndrome, or other developmental and epileptic encephalopathy Has a minimum number of seizures per 4-week period while taking 1 to 4 anti-seizure medications All medications and epilepsy interventions must be stable for 4 weeks before screening and are expected to remain stable during the study The patient/parent/caregiver is able and willing to attend study visits, complete the diary and take study drug as instructed Key Exclusion Criteria: Current or past history of cardiovascular or cerebrovascular disease, such as cardiac valvulopathy, myocardial infarction, stroke, pulmonary arterial hypertension or abnormal blood pressure Has glaucoma, renal impairment, liver disease or any other medical condition that would affect study participation or pose a risk to the subject Current or recent history of moderate or severe depression, anorexia nervosa, bulimia or at risk of suicidal behavior Currently taking anorectic agents, monoamine oxidase inhibitors; serotonin agonists or antagonists including fenfluramine, atomoxetine, vortioxetine, or other medications for weight loss Positive test result on the drug screen, except tetrahydrocannabinol (THC) for patients taking prescribed cannabidiol
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dennis J Dlugos, MD
Organizational Affiliation
Children's Hospital of Philadelphia
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Arizona - Health Sciences Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
Arkansas Children's Hospital
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202
Country
United States
Facility Name
Rancho Los Amigos National Rehabilitation Center (RLANRC)
City
Downey
State/Province
California
ZIP/Postal Code
90242
Country
United States
Facility Name
Children's Hospital of Orange County
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Northwest Florida Clinical Research Group
City
Gulf Breeze
State/Province
Florida
ZIP/Postal Code
32561
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Advent Health Orlando
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
Facility Name
Research Institute of Orlando
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33606
Country
United States
Facility Name
Hawaii Pacific Neuroscience
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96817
Country
United States
Facility Name
Consultants in Epilepsy and Neurology
City
Boise
State/Province
Idaho
ZIP/Postal Code
83702
Country
United States
Facility Name
Northwestern University Feinberg School of Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Mid-Atlantic Epilepsy and Sleep Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20817
Country
United States
Facility Name
Spectrum Health
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49503
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Boston Children's Health Physicians LLP
City
Hawthorne
State/Province
New York
ZIP/Postal Code
10532
Country
United States
Facility Name
New York University Langone Hospital - Long Island
City
Mineola
State/Province
New York
ZIP/Postal Code
11501
Country
United States
Facility Name
Northwell Health
City
New York
State/Province
New York
ZIP/Postal Code
10075
Country
United States
Facility Name
Northeast Regional Epilepsy Group
City
Staten Island
State/Province
New York
ZIP/Postal Code
10305
Country
United States
Facility Name
OnSite Clinical Solutions LLC
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
98277
Country
United States
Facility Name
Wake Forest University School of Medicine
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
University Hospitals Cleveland Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Providence Neurological Specialties-East
City
Portland
State/Province
Oregon
ZIP/Postal Code
97213
Country
United States
Facility Name
Child Neurology Consultants of Austin
City
Austin
State/Province
Texas
ZIP/Postal Code
78757
Country
United States
Facility Name
Austin Epilepsy Care Center
City
Austin
State/Province
Texas
ZIP/Postal Code
78758
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
University of Washington Valley Medical Center
City
Renton
State/Province
Washington
ZIP/Postal Code
98055
Country
United States
Facility Name
Royal Brisbane Women's Hospital
City
Herston
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Facility Name
Queensland Children's Hospital
City
South Brisbane
State/Province
Queensland
ZIP/Postal Code
4101
Country
Australia
Facility Name
Monash Children's Hospital, Monash Health
City
Clayton
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Facility Name
Austin Health
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Facility Name
Alfred Health
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Study to Investigate LP352 in Subjects With Developmental and Epileptic Encephalopathies

We'll reach out to this number within 24 hrs