A First-in-human, Randomised, Placebo-controlled, Double-blind, Single and Multiple Dose Study to Explore the Safety, Tolerability, PK and PD of Oral Doses of ONO-7684 in Healthy Subjects Under Fed and Fasted Conditions
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- Number of participants with clinically significant changes in vital signs (Part A & B)
研究概览
简要总结
This is a first in human study to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of ONO-7684 in healthy adult volunteers. This study will be conducted in 2 parts: Part A is a single-ascending dose and Part B is a multiple-ascending dose.
详细描述
This study aims to obtain safety, tolerability, pharmacokinetic and pharmacodynamic data when ONO-7684 is administered orally as single doses and as multiple doses to healthy subjects. The study will consist of 2 parts: A single ascending dose (SAD) phase (Part A); a multiple ascending dose (MAD) phase (Part B). One cohort of Part A will receive ONO-7684 under both fasted and fed conditions to investigate the effect of food.
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
- Double (Participant, Investigator)
盲法说明
Double-blinded
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
- •18-55 years
- •normotensive male volunteers, or female volunteers of non-childbearing potential (Part B only)
- •body mass index 18.0-30.0 kg/m2
- •deemed healthy on the basis of a clinical history, physical examination, ECG, vital signs, and laboratory tests of blood and urine
- •registered with a General Practitioner (GP) in the UK
- •agree to use an effective method of contraception
- •able to give fully informed written consent
排除标准
- •Positive tests for hepatitis B & C, HIV
- •severe adverse reaction to any drug
- •sensitivity to trial medication
- •drug or alcohol abuse
- •current smoker or use of nicotine containing products in the previous 6 months
- •vegetarians or vegans, or unwilling to eat a high-fat breakfast (Part A food effect cohorts only)
- •use of strong CYP3A4/5 or P-glycoprotein inhibitors or inducers, anticoagulants, antiplatelet agents, non-steroidal anti-inflammatory drugs and/or acetylsalicylic acid within the previous 30 days
- •prescription or over-the-counter medication, vitamins, herbal treatments or dietary supplements within the previous 7 days (with the exception of paracetamol [acetaminophen])
- •participation in other clinical trials of unlicensed medicines, or loss of more than 400 mL blood, within the previous 3 months or plan to donate blood or blood products in the 3 months after the trial
- •vital signs outside the acceptable range
- •clinically relevant abnormal findings at the screening assessment (including creatinine clearance, haemoglobin levels and QTcF)
- •acute or chronic illness
- •clinically relevant abnormal medical history or concurrent medical condition
- •objection by GP
- •possibility that volunteer will not cooperate
- •pre-menopausal females who are pregnant or lactating, or who are of childbearing potential
研究组 & 干预措施
ONO-7684 Part B1
Eligible subjects will receive multiple doses of ONO-7684 or placebo orally
干预措施: ONO-7684 (Drug)
ONO-7684 Placebo Part B1
Eligible subjects will receive multiple doses of ONO-7684 or placebo orally
干预措施: ONO-7684 Placebo (Drug)
ONO-7684 Part A1
Single ascending doses of ONO-7684 or placebo orally under fasted conditions
干预措施: ONO-7684 (Drug)
ONO-7684 Placebo Part A1
Single ascending doses of ONO-7684 or placebo orally under fasted conditions
干预措施: ONO-7684 Placebo (Drug)
ONO-7684 Part A2
Single doses of ONO-7684 or placebo orally under fed conditions
干预措施: ONO-7684 (Drug)
ONO-7684 Placebo Part A2
Single doses of ONO-7684 or placebo orally under fed conditions
干预措施: ONO-7684 Placebo (Drug)
结局指标
主要结局
Number of participants with clinically significant changes in vital signs (Part A & B)
时间窗: Part A: Day 1-4 & Follow-up and Part B: Day 1-15, 17 & Follow up
Pulse rate (bpm), systolic and diastolic blood pressure (mmHg), Respiratory rate (bpm)
Number of participants with clinically significant changes in laboratory safety tests (haematology, biochemistry and urinalysis) (Part A & B)
时间窗: Part A: Day-1, 1-4 & Follow up and Part B: Day-1, 1-17 & Follow up
Number of participants with abnormalities in laboratory safety tests will be reported.
Number of participants with clinically significant changes observed on 12-lead electrocardiogram (ECG) (Part A & B)
时间窗: Part A: Day 1-4 & Follow up & Part B: Day 1,3,5,7,9,11,14,17 & Follow up
Ventricular rate (beats/min), PR interval (msec), QRS interval (msec), QT (msec), QTcF interval (msec)
Number of participants with clinically significant changes in physical examination (Part A & B)
时间窗: Part A: Day -1, 1-4 & Follow-up and Part B: Day-1, 1-17 & Follow up
Number of participants with physical examination abnormalities will be reported.
Number of participants with clinically significant changes in cardiac telemetry (Part A only)
时间窗: Part A: From 0.5-1 hours pre-dose until 12 hours after dosing at Day 1
Number of participants with cardiac telemetry abnormalities will be reported.
Number of participants with adverse events (AE) (Part A & B)
时间窗: Part A: Day-1, 1-4 & Follow up and Part B: Day-1, 1-17 & Follow up
AE is any untoward medical occurrence in a subject or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
次要结局
- Pharmacokinetics (CL/F)(Day 1 through Day 4)
- Pharmacodynamic (change from baseline in aPTT activity) in serum(Part A: Day 1 through Day 4. Part B: Day 1 through Day 17)
- Pharmacokinetics (t1/2)(Part A: Day 1 through Day 4. Part B: Day 14)
- Pharmacokinetic (fe/F)(Day 1 through Day 4)
- Pharmacokinetic (Ctrough)(Day 1 through Day 14)
- Pharmacokinetic (AUCtau)(Day 14)
- Pharmacokinetics (AUClast)(Part A: Day 1 through Day 4. Part B: Day 14)
- Pharmacokinetics (%AUCextrap)(Part A: Day 1 through Day 4. Part B: Day 14)
- Pharmacokinetics (Aet)(Day 1 through Day 4)
- Pharmacodynamic (change from baseline in PT activity) in serum(Part A: Day 1 through Day 4. Part B: Day 1 through Day 17)
- Pharmacokinetics (Cmax)(Part A: Day 1 through Day 4. Part B: Day 1 and Day 14)
- Pharmacokinetics (AUCinf)(Part A: Day 1 through Day 4. Part B: Day 14)
- Pharmacokinetics (AUCt)(Part A: Day 1 through Day 4. Part B: Day 1)
- Pharmacokinetics (Terminal Rate Constant)(Day 1 through Day 4)
- Pharmacokinetic (CLr)(Day 1 through Day 4)
- Pharmacokinetic (CLSS/F)(Day 14)
- Pharmacokinetics (tmax)(Part A: Day 1 through Day 4. Part B: Day 1 and Day 14)
- Pharmacodynamic (correlation of aPTT and FXIa activity) in serum(Part A: Day 1 through Day 4. Part B: Day 1 through Day 17)
- Pharmacokinetic (VZ/F)(Day 14)
- Pharmacodynamic (change from baseline in PT-INR activity) in serum(Part A: Day 1 through Day 4. Part B: Day 1 through Day 17)
- Pharmacodynamic (change from baseline in FXIa activity) in serum(Part A: Day 1 through Day 4. Part B: Day 1 through Day 17)