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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 34
- 主要终点
- Columbia-Suicide Severity Rating Scale (C-SSRS) Response
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: LP352 (Drug)
Placebo
Placebo for LP352
干预措施: Placebo (Drug)
结局指标
主要结局
Columbia-Suicide Severity Rating Scale (C-SSRS) Response
时间窗: Baseline 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 Period
时间窗: Baseline up to Day 75
Treatment-emergent Adverse Events
时间窗: 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
Patient Health Questionnaire-9 Total Score and Question 9 Score
时间窗: Baseline 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 Period
时间窗: Baseline up to Day 75
次要结局
- Modeled Estimate of Observed Plasma Concentration Just Prior to Dosing(Baseline up to Day 75)
- Modeled Estimate of Average Plasma Concentration(Baseline up to Day 75)
- Observed Plasma Concentrations of LP352 by Time and Dose(Baseline up to Day 75)
- Correlation of Plasma Concentration with Incidence of Treatment-emergent Adverse Events(Baseline up to Day 75)
- Correlation of Plasma Concentration with Seizure Frequency(Baseline up to Day 75)
- Observed and Change from Baseline Prolactin Concentration During the Treatment Period(Baseline up to Day 75)