Developmental and Epileptic Encephalopathy, Dravet Syndrome, Lennox-Gastaut Syndrome
Conditions
Keywords
CDKL5 deficiency disorder, developmental and epileptic encephalopathy, Dravet Syndrome, epilepsy, Lennox-Gastaut Syndrome, treatment resistant epilepsy, tuberous sclerosis complex
Brief summary
The objective of this study is to assess the long-term safety, tolerability, and efficacy of adjunctive therapy of LP352 in subjects with developmental and epileptic encephalopathies who completed participation in Study LP352-201.
Detailed description
This Phase 2, multicenter, open-label, multiple-dose extension clinical study is designed to evaluate long-term safety of LP352 in subjects with developmental and epileptic encephalopathy who completed Study LP352-201. The study consists of a Screening Period (Day -1) and a 50-week open-label Treatment Period that includes a 15-day Up-titration Period (during which time subjects will titrate up to their highest tolerated doses) and an open-label Maintenance Period (48 weeks). The Treatment Period will be followed by a Down-titration/Taper Period (up to 15 days) and Follow-up Period (14 days after completion of down-titration). The starting dose of up-titration will be 6 mg TID. The target final maintenance doses are 6 mg TID, 9 mg TID, and 12 mg TID after a 15-day up-titration period, if tolerated.
Interventions
DRUGLP352, bexicaserin
LP352 6 mg, 9 mg or 12 mg administered three times daily, orally or through G-tube
Sponsors
Longboard Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Male or non-pregnant, non-lactating female, age 12 to 65 years who have satisfactorily completed study LP352-201 2. Diagnosis of Dravet syndrome, Lennox-Gastaut syndrome, or other developmental and epileptic encephalopathy 3. The patient/parent/caregiver is able and willing to attend study visits, complete the diary and take study drug as instructed
Exclusion criteria
1. Had an SAE in Study LP352-201 that was definitely, probably, or possibly related to exposure to study drug 2. Current or past history of cardiovascular or cerebrovascular disease, such as cardiac valvulopathy, myocardial infarction, stroke, pulmonary arterial hypertension or abnormal blood pressure 3. Has glaucoma, renal impairment, liver disease or any other medical condition that would affect study participation or pose a risk to the subject 4. Current or recent history of moderate or severe depression, anorexia nervosa, bulimia or at risk of suicidal behavior 5. Currently taking anorectic agents, monoamine oxidase inhibitors; serotonin agonists or antagonists including fenfluramine, atomoxetine, vortioxetine, or other medications for weight loss 6. Positive test result on the drug screen, except tetrahydrocannabinol (THC) for patients taking prescribed cannabidiol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-emergent Adverse Events | Baseline up to Week 52 | Incidence and severity of treatment-emergent 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 | Baseline up to Week 52 | Type of Suicidal Ideation, Intensity (1 - 5, with 5 being most severe), Suicidal Behavior |
| Patient Health Questionnaire-9 Total Score and Question 9 Score | Baseline up to Week 52 | Severity Rating Scale: 0 - 27; higher scores indicate greater severity of depressive disorder |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Requiring Rescue Medication During the Treatment Period | Baseline to Week 50 | — |
| Percent Change from Baseline in the Number of Episodes of Status Epilepticus During the Treatment Period | Baseline to Week 50 | — |
| Percent Change from Baseline in Observed Countable Motor Seizure Frequency During the Treatment Period | Baseline to Week 50 | Baseline Used for Seizure Frequency = Baseline from Study LP352-201 and Baseline from Study LP352-202 |
| Percentage Change from Baseline in Non-motor and Difficult to Count Seizures | Baseline to Week 50 | — |
| LGS: Percentage Change from Baseline in the Frequency of Observed Drop Seizures Over the Treatment Period | Baseline to Week 50 | — |
| Percent of Subjects with Countable Motor Seizure-free Days During the Treatment Period | Baseline to Week 50 | — |
| Proportion of Subjects with > 50% Reduction in Total Seizures During the Treatment Period | Baseline to Week 50 | — |
| Percent Reduction in Individual Seizure Type During the Treatment Period | Baseline to Week 50 | — |
Countries
Australia, United States
Outcome results
None listed