A Phase I Dose Escalation Study of Harmine in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Number of Participants With Dose Limiting Toxicity (DLT)
研究概览
简要总结
The present study is a phase 1 dose escalation study of harmine in healthy volunteers. The primary goal of the trial is to determine the maximum tolerated dose of harmine.
详细描述
The present study is a phase 1 dose escalation study of harmine in healthy volunteers. The primary goal of the trial is to determine the maximum tolerated dose of harmine. Harmine will be administered in an open-label, dose escalation design that will use the continual reassessment method to inform the next dose to test in a subject. There will be a total of seven possible doses that include 100 mg, 200 mg, 300 mg, 500 mg, 700 mg, 900 mg and 1200 mg. Each study subject will receive a single oral dose of harmine in this single ascending dose design. On the treatment day, subjects will undergo continuous medical monitoring. All adverse events will be documented and events that qualify as dose limiting toxicities (DLTs) will be used to inform dosing for the subsequent subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Harmine Dose
There will be a total of seven possible doses that include 100 mg, 200 mg, 300 mg, 500 mg, 700 mg, 900 mg and 1200 mg. Each study subject will receive a single oral dose of harmine in this single ascending dose design.
干预措施: Harmine Hydrochloride Capsules (Drug)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicity (DLT)
时间窗: 24 hours
DLT which is defined if have any one of the following: Patient Rated Inventory of Side Effects (PRISE): 0-51, higher scores indicate more adverse events observed Brief Psychiatric Rating Scale (BPRS): 4 - 28, higher scores indicate more symptoms of psychosis Vitals: blood pressure and heart rate will all be measured - anything outside of the following ranges will be noted: * Symptomatic hypotension, or \> 20% decrease in systolic blood pressure (SBP) from pre-dosing and an absolute SBP \< 90; or * Symptomatic hypertension, or \> 20% increase in SBP or diastolic blood pressure (DBP) from predosing and absolute SBP \> 170 or DBP \> 95; * New onset tachycardia (heart rate \>100 bpm) and \>20% increase from pre-dosing; or symptomatic bradycardia (heart rate \<60 bpm) and \> 20% decrease from pre-dosing. * Signs and symptoms of cardiac ischemia, defined by acute ischemic changes on ECG with or without concomitant symptoms
Maximum Tolerated Dose (MTD) of Oral Harmine HCl Based on Dose Limiting Toxicity (DLT)
时间窗: 24 hours
The MTD was determined to be between 100 and 200mg and is weight-based.
次要结局
- Visual Analog Scale (VAS) - Nausea(baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hours)
- Visual Analog Scale (VAS) - Hunger(baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hours)
- Visual Analog Scale (VAS) - Feeling High/Intoxicated(baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hours)
- Visual Analog Scale (VAS) - Drowsiness(baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hours)
- Visual Analog Scale (VAS) - Anxiety(baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hours)
- Visual Analog Scale (VAS) - Depressed Mood(baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hours)
- Visual Analog Scale (VAS) - Happy Mood(baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hours)
- Visual Analog Scale (VAS) - Excitement(baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hours)
- Visual Analog Scale (VAS) - Feeling of Control(baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hours)
- Visual Analog Scale (VAS) - Vividness of Image(baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hours)
- Profile of Mood States Bipolar Scale (POMS-Bi): Composed-Anxious Scale(Baseline, 2, 6, 7, 8, and 24 hours)
- Profile of Mood States Bipolar Scale (POMS-Bi): Agreeable-Hostile Scale(Baseline, 2, 6, 7, 8, and 24 hours)
- Profile of Mood States Bipolar Scale (POMS-Bi): Elated-Depression Scale(Baseline, 2, 6, 7, 8, and 24 hours)
- Profile of Mood States Bipolar Scale (POMS-Bi): Confident-Unsure Scale(Baseline, 2, 6, 7, 8, and 24 hours)
- Profile of Mood States Bipolar Scale (POMS-Bi): Energetic-Tired Scale(Baseline, 2, 6, 7, 8, and 24 hours)
- Profile of Mood States Bipolar Scale (POMS-Bi): Clearheaded-Confused Scale(Baseline, 2, 6, 7, 8, and 24 hours)
- Perceived Stress Scale (PSS)(24 hours)
- Patient Rated Inventory of Side Effects (PRISE)(24 hours)
- Brief Psychiatric Rating Scale (BPRS)(Baseline, 2, 6, 7, 8, and 24 hours)
- Columbia Suicide Severity Rating Scale (C-SSRS)(24 hours)
研究者
James Murrough
Associate Professor
Icahn School of Medicine at Mount Sinai