One Centre Single Ascending Dose and Double Blind Multiple Ascending Dose, Safety and Pharmacokinetics Phase I Study of CPL500036 Compound in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Determination of maximum tolerated dose (MTD) or administration of the maximum dose provided in the protocol after single and multiple oral administration of IMP.
研究概览
简要总结
The planned study is to determine the safety and pharmacokinetic properties of CPL500036 compound after single and multiple (two weeks) administration in healthy volunteers.
详细描述
This is to be one-centre, single ascending dose and double-blind multiple ascending dose two part study of CPL500036 compound in healthy volunteers.
PART A is a single dose, open-label part with CPL500036 compound administered with dose escalation between cohorts.
PART B is a multiple, double-blind part with CPL500036 compound administered for 14 days with dose escalation between cohorts. Participants in this part are to be randomized to receive Investigational Medicinal Product (IMP) or placebo in 3:1 ratio.
Safety and pharmacokinetic properties of CPL500036 compound is to be determined following different doses in single oral IMP administration in PART A and different doses of IMP administered orally for two weeks in PART B.
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
Only PART B will be double-blind
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
- •Caucasian female or male,
- •Age: 18-55 years old, inclusive,
- •Body-mass index (BMI): ≥18.5 kg/m^2 and <29.9 kg/m^2,
- •Non-smoker and nonuser of tobacco products for at least 3 months before screening,
- •Physical examination without any clinically relevant abnormality,
- •Laboratory values not clinically significant,
- •Volunteer (or his/her partner) of childbearing potential willingness to use acceptable forms of contraception.
排除标准
- •Known allergy or hypersensitivity to other drugs similar in structure or class to CPL500036 compound, or to any excipients of the formulation,
- •Any known significant current or past acute or chronic disease or condition,
- •Participation in other clinical trial within 90 days preceding the screening,
- •Blood drawn within 30 days prior to inclusion to the study (more or equal to 300mL),
- •Positive results from pregnancy test for female participants,
- •Lactation in women participants,
- •Hypotension or hypertension in medical history,
- •Long QT interval syndrome or is under the treatment with antiarrhythmic drugs,
- •Narcotic, alcohol addiction or abuse,
- •Participant who adhere to a special diet (e.g. low calories, vegetarian).
研究组 & 干预措施
CPL500036
PART A: 7 cohorts are to receive single dose of IMP. Each participant is to take single dose of IMP. There is to be dose escalation between cohorts.
PART B: 4 cohorts are to receive multiple dose of IMP. Each participant is to take IMP once daily for 14 days. There is to be dose escalation between cohorts.
干预措施: CPL500036 compound (Drug)
Placebo
PART B: 2 Participants from 4 cohorts (total of 8 people) are to receive masking placebo capsules once daily for 14 days. There is to be dose escalation between cohorts. Participants are to be randomized within cohorts.
干预措施: Placebo (Drug)
结局指标
主要结局
Determination of maximum tolerated dose (MTD) or administration of the maximum dose provided in the protocol after single and multiple oral administration of IMP.
时间窗: up to 24 hours after single administration of IMP in PART A and up to 24 hours after the last IMP administration in PART B
MTD is defined as the highest dose for which no more than 1 of the 6 treated volunteers (less than 1/3) exhibits dose limiting toxicity (DLT).
Safety and tolerability of IMP after single and multiple oral administration based on laboratory values, vital signs, ECG, physical examinations and Adverse Events monitoring.
时间窗: up to 14 days in PART A and up to 28 days in PART B of the study
Participants are to be closely observed to assure maximal safety and to collect occurrence of all adverse events. All participants are to be monitored for clinically relevant changes in physical examination, vital signs, 12-lead ECG assessment and deviations from normal in clinical laboratory results (complete blood count, blood chemistry, urinalysis). To follow-up on all study participants telephone calls with a request for information regarding their health condition are to be made.
次要结局
- AUC(0-72) - area under the plasma concentration - time curve from time 0 to 72h after IMP administration for CPL500036(up to 72 hours after administration of IMP in PART A)
- C (1,t) - CPL500036 concentration(Determined on Day 2, 3, 4, 5, 6, 8, 9, 10, 11, 12 and 13 in PART B.)
- Cmax - maximum CPL500036 plasma concentration(up to 72 hours after administration of IMP in PART A and up to 24 hours after the IMP administration determined on Day 1, 7 in PART B and up to 72 hours after the last IMP administration on Day 14 in PART B)
- AUC(0-24) - area under the plasma concentration - time curve from time 0 to 24h after IMP administration for CPL500036(up to 24 hours after administration of IMP in PART A and up to 24 hours after the IMP administration determined on Day 1, 7 and 14 in PART B)
- AUC(0-inf) - area under the plasma concentration - time curve from time 0 to infinity time for CPL500036(up to 72 hours after administration of IMP in PART A and up to 24 hours after the IMP administration determined on Day 1, 7 in PART B and up to 72 hours after the last IMP administration on Day 14 in PART B)
- Tmax - time to reach maximum CPL500036 concentration(up to 72 hours after administration of IMP in PART A and up to 24 hours after the IMP administration determined on Day 1, 7 in PART B and up to 72 hours after the last IMP administration on Day 14 in PART B)
- Kel - terminal elimination rate constant(up to 72 hours after administration of IMP in PART A and up to 24 hours after the IMP administration determined on Day 1, 7 in PART B and up to 72 hours after the last IMP administration on Day 14 in PART B)
- T1/2 - The plasma elimination half-life for CPL500036 compound(up to 72 hours after administration of IMP in PART A and up to 24 hours after the IMP administration determined on Day 1, 7 in PART B and up to 72 hours after the last IMP administration on Day 14 in PART B)
- C (Tmax, t) - CPL500036 concentration(Determined on Day 2, 3, 4, 5, 6, 8, 9, 10, 11, 12 and 13 in PART B.)
- Amount of CPL500036 in each urine collection sample(up to 72 hours after administration of IMP in PART A and up to 24 hours after the IMP administration determined on Day 1, 7 in PART B and up to 72 hours after the last IMP administration on Day 14 in PART B)
- Ae - total amount of CPL500036 excreted in urine(up to 72 hours after administration of IMP in PART A and up to 24 hours after the IMP administration determined on Day 1, 7 in PART B and up to 72 hours after the last IMP administration on Day 14 in PART B)
- Clr - renal clearance(up to 72 hours after administration of IMP in PART A and up to 24 hours after the IMP administration determined on Day 1, 7 in PART B and up to 72 hours after the last IMP administration on Day 14 in PART B)
- Excretion rate(up to 72 hours after administration of IMP in PART A and up to 24 hours after the IMP administration determined on Day 1, 7 in PART B and up to 72 hours after the last IMP administration on Day 14 in PART B)