A First-in-Human Randomized, Double-blind, Placebo-controlled, Fed-fasted, Gender, Single and Multiple Ascending Oral Dose Study, to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of OMT-28 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 75
- 试验地点
- 1
- 主要终点
- Safety assessed by frequency and nature of treatment-emergent adverse events
研究概览
简要总结
The aim of this first-in-human study is to assess the safety, tolerability, PK and exploratory pharmacodynamics (PD) of single and multiple oral ascending doses of OMT-28 in healthy male subjects to support further clinical development of OMT-28 in the indication of atrial fibrillation (AF) and to obtain data on food and gender effects of OMT-28 to guide dosing for Phase II trials.
详细描述
This first-in-human study will be carried out in one study center involving multiple steps. Up to 100 healthy male and female subjects will be enrolled. The study consists of 4 parts:
- a single ascending dose (SAD) part
- a multiple ascending dose (MAD) part
- a single dose, double cross-over food effect (FE) part.
- a single dose gender effect part (female subjects group) The safety and PK data will be evaluated by the DSMC after each cohort to decide on further dose escalation.
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
SAD, MAD and Gender parts: double blind randomized. Food Effect part: open label, crossover design
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •In general good physical health as determined by medical and surgical history, physical examination, 12 lead ECG, vital signs, and clinical laboratory tests
- •Normal blood pressure (Systolic Blood Pressure (SBP) between 100 to 140 mmHg (both inclusive); Diastolic Blood Pressure (DBP) ≥55, ≤89 mmHg) measured after 5 min rest in supine position.
- •SAD, MAD, and FE part: male of 18 to 45 years (inclusive) of age.
- •Gender effect part: female of 18 to 45 years (inclusive) of age.
排除标准
- •More than moderate smoker (> 10 cigarettes/day).
- •More than moderate alcohol consumption (> 35 g of ethanol regularly per day or > 245 g regularly per week).
- •Use of any medication
- •One or more key safety laboratory parameters out of normal range Gender effect part Pregnant or breastfeeding women and of childbearing potential Previous assignment to treatment during this study.
研究组 & 干预措施
OMT-28-SAD
OMT-28-SAD, Single ascending dose levels 1 - 3 of OMT-28 (15, 30, 60 mg) Oral, healthy young male
干预措施: OMT-28 (Drug)
OMT-28-MAD
Multiple ascending dose of dose levels 1 - 3 of OMT-28 over 14 days (4, 12, 36 mg) Oral, healthy young male
干预措施: OMT-28 (Drug)
OMT-28- Food Effect
Single dose of OMT-28 (4 mg) Oral, healthy young male
干预措施: OMT-28 (Drug)
OMT-28-Gender
Single dose of OMT-28 (4 mg) Oral, healthy non-child bearing potential female
干预措施: OMT-28 (Drug)
Placebo-SAD
Single dose levels 1 - 3 of matching placebo, Oral, healthy young male
干预措施: Matching Placebo (Other)
Placebo MAD
Multiple dose levels 1 - 3 of matching placebo over 14 days Oral, healthy young male
干预措施: Matching Placebo (Other)
Placebo-Gender
Single dose of matching Placebo Oral, healthy non-child bearing potential female
干预措施: Matching Placebo (Other)
结局指标
主要结局
Safety assessed by frequency and nature of treatment-emergent adverse events
时间窗: From Day 1 to Day 21
次要结局
- Pharmacokinetics (PK) measured by Cmax of OMT-28 in plasma in the SAD(From Day 1 to Day 21)
- Pharmacokinetics (PK) measured by AUC0-24h of OMT-28 in plasma after single dosing in the SAD(From Day 1 to Day 28)
- Pharmacokinetics (PK) measured by AUC0-τ after multiple dosing on Day 7 and 14 in the MAD(From Day 7 to Day 14)
- Pharmacokinetics (PK) of OMT28 measured Cmax after multiple dosing on Day 7 and 14 in the MAD(From Day 7 to Day 14)
- Pharmacokinetics (PK) in Food Effect and Gender Part measured by AUC0-t of OMT-28 in plasma(From Day 1 to Day 21 (Gender) and Day 28 (F&E))
- Pharmacokinetics (PK) in Food Effect and Gender Part measured by AUC0-∞ of OMT-28 in plasma(From Day 1 to Day 21 (Gender) and Day 28 (F&E))
- Pharmacokinetics (PK) of OMT28 in Food Effect and Gender Part measured by Cmax of OMT-28 in plasma(From Day 1 to Day 21 (Gender) and Day 28 (F&E))
- Change-from-baseline of QTcF (∆QTcF)(From baseline to Day 28)
- Change from-baseline of heart rate(From baseline to Day 28)
- Change from-baseline of PR interval in ECG(From baseline to Day 28)
- Change from-baseline of QRS interval (∆HR, ∆PR and ∆QRS)(From baseline to Day 28)
- Pharmacokinetics (PK) measured by AUC0-t of OMT-28 in plasma in the SAD(From Day 1 to Day 21)
- Pharmacokinetics (PK) measured by AUC0-∞ of OMT-28 in plasma in the SAD(From Day 1 to Day 21)