A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Escalating Doses of LH-001 in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 56
- 试验地点
- 2
- 主要终点
- Percentage of participants who experience at least one treatment-emergent AE
研究概览
简要总结
The purpose of this clinical trial is to evaluate the safety and tolerability of LH-001 when administered as an oral, single or multiple dose(s) at ascending dose levels in healthy participants.
详细描述
This is a first-in-human, randomized, double-blinded, placebo-controlled study. This study consists of two parts: (1) single ascending doses in 4 cohorts (SAD) and (2) 14-day multiple ascending doses in 3 cohorts (MAD). Cohorts may be added or removed if needed due to safety considerations or deviations of actual PK parameters from predicted values.
The SAD study consists of a screening visit, a 2-day inpatient stay (Day 1-2), a return visit for safety assessments on Day 3, Day 4, and Day 8.
The MAD study consists of a screening visit, a 2-day inpatient stay (Day 1-2), daily return for dosing and safety assessments (Day 3-13), a 2-day inpatient stay (Day 14-15), and a follow-up by phone (Day 21).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The investigators and participants will remain blinded throughout the study. At the completion of each cohort, the statistician will be unblinded to analyze data.
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy males or females aged 18-60 years at the time of consent
- •Must provide written informed consent
- •Physically and mentally able and willing to participate in the safety and other assessments including staying overnight
- •BMI 18-29.9 kg/m2
- •Sexually active male participants, sexually active female participants of childbearing potential, and their sexual partners are to adhere to the contraception requirements. These requirements include utilizing highly effective birth control (including hormonal methods, intrauterine devices, and/or barrier methods) from the screening phase through the completion of the last study follow-up. Note, the barrier method may not be used as a standalone method and must be combined with an additional approved method.
- •Participants taking non-prescribed medication must cease taking the medication for at least 48 hours prior to dosing of LH-001.
排除标准
- •Taking any prescription medications outlined in the prohibited/conditional drug list (see Section 6.8.1)
- •History or presence of gastrointestinal, renal, or hepatic disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
- •History or presence of major disorder of any other major organ system (cardiovascular, respiratory, central nervous system, or endocrine system)
- •History of cancer within 5 years of consent (exceptions are squamous and basal cell carcinomas of the skin)
- •Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks prior to dosing.
- •History or presence of alcohol or substance abuse
- •History of chronic or current use of recreational or illicit drugs
- •History of, or treatment for, major psychiatric illness
- •History of, or treatment for, seizures or epilepsy
- •Pregnant or breast-feeding females
- •History of, or treatment for, an autoimmune disease (e.g., Rheumatoid Arthritis, Multiple Sclerosis, Myasthenia Gravis, etc.)
- •History of asplenia, hyposplenia, or splenectomy
- •History or presence of drug hypersensitivity
- •Poor venous access
- •Receipt of investigational therapy within 4 months prior to screening
- •Current or previous use of systemic corticosteroids or other systemic immunosuppressive agents 4 weeks prior to dosing
- •Current or previous use of NMDA antagonists 4 weeks prior to dosing
- •Clinically significant findings in the opinion of the investigator in the laboratory, physical examination, or vital sign assessments
- •Evidence of active Hepatitis B, Hepatitis C, or HIV on laboratory testing
- •Any clinically significant ECG abnormality in the opinion of the investigator
- •Plasma or blood donation within the last 4 weeks
- •Positive drug or alcohol screen
- •Any contraindication to or unable to tolerate a LP, for those who consented to the procedure, including the use of anti-coagulant medications. Daily administration of 81 mg aspirin will be allowed
- •Any concurrent condition that, in the opinion of the investigator, would interfere with the evaluation of LH-001
- •Participants who answer "Yes" on the C-SSRS Suicidal Ideation Item 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) and whose most recent episode meeting criteria for this C-SSRS Item 4 occurred within the last 6 months, OR Subjects who answer "Yes" on the C-SSRS Suicidal Ideation Item 5 (Active Suicidal Ideation with Specific Plan and Intent) and whose most recent episode meeting criteria for this CSSRS Item 5 occurred within the last 6 months OR Subjects who answer "Yes" on any of the 5 C-SSRS Suicidal Behavior Items (actual attempt, interrupted attempt, aborted attempt, preparatory acts, or behavior) and whose most recent episode meeting criteria for any of these 5 C-SSRS Suicidal Behavior Items occurred in the last 2 years
研究组 & 干预措施
SAD Cohort 3
Participants will be administered a single 50 mg dose of LH-001
干预措施: LH-001 (Drug)
SAD Placebo cohorts 1, 2, 3 and 4
Participants will be administered a single dose of placebo
干预措施: Placebo (Drug)
MAD Placebo cohorts 1, 2 and 3
Participants will be administered multiple doses of placebo
干预措施: Placebo (Drug)
SAD Cohort 1
Participants will be administered a single 12.5 mg dose of LH-001
干预措施: LH-001 (Drug)
SAD Cohort 2
Participants will be administered a single 25 mg dose of LH-001
干预措施: LH-001 (Drug)
SAD Cohort 4
Participants will be administered a single 100 mg dose of LH-001
干预措施: LH-001 (Drug)
MAD Cohort 1
Participants will be administered multiple 25 mg doses of LH-001
干预措施: LH-001 (Drug)
MAD Cohort 2
Participants will be administered multiple 50 mg doses of LH-001
干预措施: LH-001 (Drug)
MAD Cohort 3
Participants will be administered multiple 100 mg doses of LH-001
干预措施: LH-001 (Drug)
结局指标
主要结局
Percentage of participants who experience at least one treatment-emergent AE
时间窗: 8 days for SAD and 21 days for MAD
Percentage of participants who discontinue due to an AE
时间窗: 8 days for SAD and 21 days for MAD
Percentage of participants who meet the markedly abnormal criteria for vital sign measurements at least once post-dose
时间窗: 8 days for SAD and 21 days for MAD
Percentage of participants who meet the markedly abnormal criteria for safety ECG parameters at least once post-dose
时间窗: 8 days for SAD and 21 days for MAD
Percentage of participants who meet the markedly abnormal criteria for safety laboratory tests at least once post-dose
时间窗: 8 days for SAD and 21 days for MAD
次要结局
- Maximum concentration (Cmax)(Day 1 for all cohorts and Day 14 for MAD cohorts)
- Time to reach maximum concentration (Tmax)(Day 1 for all cohorts and Day 14 for MAD cohorts)
- Time for LH-001 concentration to fall to half of its original value (T½)(Day 1 for all cohorts and Day 14 for MAD cohorts)
- Area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration (AUC0-last)(Day 1 for all cohorts and Day 14 for MAD cohorts)
研究者
Chien-Liang Lin
Professor of Neuroscience
Ohio State University