A Phase I Study To Investigate The Safety, Tolerability And Pharmacokinetic Profile Of OZ439 In Healthy Male and Female Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 63
- 试验地点
- 1
- 主要终点
- Adverse Events
研究概览
简要总结
OZ439 is a synthetic trioxolane that has potential value as a peroxide antimalarial agent.
This was a Phase I, single-centre, multi-component, double-blind, randomised, placebo-controlled study in healthy male and female subjects. The study was conducted in 3 parts:
- Part A investigated the safety, tolerability and pharmacokinetics (PK) of single oral escalating doses of OZ439. Up to 6 dose levels will be investigated to estimate dose proportionality.
- Part B, the effect of food on a single oral dose of OZ439 was investigated in a 2-way crossover design.
- Part C investigated the safety, tolerability and PK profile of multiple oral doses of OZ439.
The starting oral dose was 50 mg and the maximum single dose to be administered did not exceed 1600 mg per subject. The maximum duration of dosing proposed was 3 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Healthy male//female subjects between 18- 55 years of age (inclusive).
- •Body mass Index (BMI) between 18 - 30 kg/m2, inclusive; and a total body weight >60 kg (132 lbs).
- •Healthy as determined by pre-study medical history, PE, 12 Lead ECG.
- •Females of childbearing potential must use 1 of birth control methods throughout study and for 30 days after last dose of study drug:
- •Surgically sterile (bilateral tubal ligation, hysterectomy, bilateral oophorectomy) 6 months minimum prior to first dose of study drug.
- •Intrauterine device (IUD) in place for at least 3 months prior to first dose of study drug.
- •Barrier methods (condom or diaphragm) with spermicide starting at least 14 days prior to first dose of study drug through 30 days after last dose of study drug.
- •Surgical sterilization of the partner(s) (vasectomy with zero sperm count for 6 months minimum prior to the first dose of study drug).
- •Hormonal contraceptives starting at least 3 months prior to first dose of study drug. In addition, subjects must agree to use a barrier method (condom or diaphragm) with spermicide at least 14 days prior to first dose of study drug through 30 days after the last dose of study drug.
- •Post-menopausal women with amenorrhea for at least 1 year will be eligible confirmed by FSH.
- •Male subjects must agree to use double barrier method of contraception, from time of first dose of study drug through 90 days after last dose of study drug and must also agree to not donate sperm for 90 days after last dose of study drug. Clinical laboratory tests within the reference ranges.
- •Able/willing to give written informed consent.
- •Willing/to adhere to lifestyle guideline restrictions outlined in protocol.
- •Willing and able to be confined to Clinical Research Unit as required by the protocol.
排除标准
- •Evidence/history of clinically significant oncologic, pulmonary, hepatic, cardiovascular, hematologic, metabolic, neurological, immunologic, nephrologic, endocrine, psychiatric disease, current infection.
- •Evidence/history of clinically significant gastrointestinal (some exclusions exist) disease, current infection.
- •Any condition that affecting drug absorption, e.g., gastrectomy.
- •History of post-antibiotic colitis.
- •Breast feeding.
- •QTc greater than 450 msec for males and 470 msec for females as corrected by the Bazett formula.
- •History of drug or alcohol abuse within the past 2 years prior to Screening.
- •Tobacco users
- •Received investigational drug/ participated in another research study within 30 days of first dose of study drug in any part of study.
- •Use of prescription drugs within 14 days prior to the first dose of study drug in Period 1, or need for any antibiotic during study.
- •Received any non prescription meds, vitamins, herbal/dietary supplements within 7 days of administration of first dose of study drug in Period 1 (exceptions exist)
- •Consumed alcohol within 72 hours of Day -1 in any part of study, or have a positive alcohol screen at screening or each admission to Clinical Research Unit (CRU).
- •Consumed grapefruit juice or juices containing grapefruit or ate grapefruit within 7 days prior to first dose of study drug in any part of study.
- •Positive serum pregnancy test at the Screening Visit or on Day -1 prior to inclusion in any part of the study.
- •Positive test for HIV-1, HBsAg,HCV.
- •Positive urine drug screen at Screening or admission to CRU.
- •History of intolerance/ hypersensitivity to artemisinins.
- •Likelihood of requiring treatment during study period with drugs not permitted by protocol.
- •Subjects who have donated blood or experienced significant blood loss within 60 days of screening for study.
- •Subjects whose hemoglobin is <12.5 g/dL for males/ <11.5 g/dL for females.
- •Any concern by investigator regarding safe participation of the subject in study or for any other reason investigator considers subject inappropriate for participation in study.
研究组 & 干预措施
Part A - 200mg Single Dose
OZ439 Single doses of 200mg (capsules)
干预措施: OZ439 200mg API capsules (Drug)
Part A - 400mg Single Dose
OZ439 Single doses of 400mg (capsules)
干预措施: OZ439 400mg API capsules (Drug)
Part A - 400mg AD Single Dose
OZ439 Single doses of 400mg (aqueous dispersion)
干预措施: OZ439 400mg aqueous dispersion (Drug)
Part A - Placebo
Placebo control for Single rising Part A
干预措施: Placebo (Drug)
Part B - 800mg AD Single Dose Fast
Single dose of OZ439 800mg aqueous dispersion administered under fast conditions
干预措施: OZ439 800mg aqueous dispersion (Drug)
Part A - 400mg Single Dose + Food
OZ439 Single doses of 400mg (capsules) administered with food.
干预措施: OZ439 400mg API capsules (Drug)
Part A - 800mg Single Dose
OZ439 Single doses of 800mg (capsules)
干预措施: OZ439 800mg API capsules (Drug)
Part A - 50 mg Single Dose
OZ439 Single doses of 50mg (capsules)
干预措施: OZ439 50mg API capsules (Drug)
Part A - 100mg Single Dose
OZ439 Single doses of 100mg (capsules)
干预措施: OZ439 100mg API capsules (Drug)
Part A - 1200mg Single Dose
OZ439 Single doses of 1200mg (capsules)
干预措施: OZ439 1200mg API capsules (Drug)
Part A - 800mg AD Single Dose
OZ439 Single doses of 800mg (aqueous dispersion)
干预措施: OZ439 800mg aqueous dispersion (Drug)
Part C - 200mg AD Multiple Dose
200mg aqueous solution OZ439 or placebo once daily for 3 days fasted
干预措施: OZ439 200mg aqueous dispersion (Drug)
Part C - 400mg AD Multiple Dose
400mg aqueous solution OZ439 or placebo once daily for 3 days fasted
干预措施: OZ439 400mg aqueous dispersion (Drug)
Part C - 800mg AD Multiple Dose
800mg aqueous solution OZ439 or placebo once daily for 3 days fasted
干预措施: OZ439 800mg aqueous dispersion (Drug)
Part A - 1600mg AD Single Dose
OZ439 Single doses of 800mg (aqueous dispersion)
干预措施: OZ439 1600mg aqueous dispersion (Drug)
Part B - 800mg AD Single Dose Fed
Single dose of OZ439 800mg aqueous dispersion administered under fed conditions
干预措施: OZ439 800mg aqueous dispersion (Drug)
Part C - Placebo
Placebo control for Multiple rising Part C
干预措施: Placebo (Drug)
结局指标
主要结局
Adverse Events
时间窗: From screening and at 10 (+/-2) days after last dose of study medication
Safety/Tolerability evaluation took into account the recorded AE profile, clinical laboratory safety tests, vital signs, 12 lead and continuous (Parts A and C) ECG monitoring, audiometry/Brainstem Auditory Evoked Potentials (BAEP) parameters (Parts A and C) including any additional tests required to evaluate any safety concerns.
次要结局
- OZ439 AUC0-t(Samples collected from Pre-dose up to 96h post dose)
- OZ439 AUC0-∝(Samples collected from Pre-dose up to 96h post dose)
- OZ439 Cmax(Samples collected from Pre-dose up to 96h post dose)
- OZ439 Tmax(Samples collected from Pre-dose up to 96h post dose)
- OZ439 t1/2(Samples collected from Pre-dose up to 96h post dose)
- OZ439 Rac(Samples collected from Pre-dose up to 96h post dose)