A Phase I Study to Investigate the Safety, Tolerability & Pharmacokinetics of Co-administered Single Doses of OZ439 and Piperaquine to Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 59
- 试验地点
- 1
- 主要终点
- Piperaquine Cmax
研究概览
简要总结
A Phase I Study to investigate the safety, tolerability & pharmacokinetics of co-administered single doses of OZ439 and Piperaquine to healthy subjects.
详细描述
Placebo-controlled, double-blind, five-cohort, 2-period (per cohort) dose-escalation study.
For each subject, the study included a screening evaluation (within 21 days of the 1st dose), dosing on 2 separate occasions (Period 1 and Period 2) and a follow-up visit (6 weeks following the final dose).
Within each cohort, subjects were randomised into two sequences to receive OZ439 in Period 1 and OZ439 plus piperaquine in Period 2 (sequence 1, 8 subjects) or OZ439-matching placebo in Period 1 and OZ439/piperaquine matching placebos in Period 2 (sequence 2, 4 subjects).
Safety and tolerability were evaluated: Physical examination, ECG assessments including a full baseline matched profile of ECG tracings, vital signs, laboratory evaluations, in particular liver function tests and adverse events.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 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 males & females, 18-55 years old
- •BMI 18 to 30kg/m2; total body weight >50kg
- •Healthy, determined by pre-study medical history, physical examination vital signs, 12 Lead ECG
- •Females of non-childbearing potential.
- •Males must agree to use a double barrier method of contraception
- •Lab tests at screening within the reference ranges
排除标准
- •Any condition that could affect drug absorption, e.g. gastrectomy, diarrhea
- •Clinically relevant abnormalities in ECG
- •Family history of sudden death or of congenital prolongation of QTc interval - History of symptomatic cardiac arrhythmias or with clinically relevant bradycardia
- •Electrolyte disturbances
- •History of drug or alcohol abuse, tobacco users
- •Participation in evaluation of any drug for 3 months before the study
- •Administration of ANY systemic medication/herbal product within 14 days of first dose of study drug.
- •unaccustomed strenuous exercise within 7 days of any study visit
- •Alcohol consumption within 24 hours of any study visit
- •Consumption of any fruit juice or food containing grapefruit within 7 days
- •Positive test for HIV-1, HBsAg or HCV
- •Positive urine drug screen at Screening or admission
- •Severe allergies/multiple drug allergies
- •Volunteers who have donated blood or experienced significant blood loss within 90 days of screening
- •Hemoglobin below lower limit of the reference range
- •Clinically relevant abnormal lab values indicative of physical illness
研究组 & 干预措施
OZ439 100 mg + PQP 160mg
100mg OZ439 single oral dose + 160mg Piperaquine single oral dose
干预措施: 100mg OZ439 single oral dose (Drug)
OZ439 100 mg + PQP 160mg
100mg OZ439 single oral dose + 160mg Piperaquine single oral dose
干预措施: 160mg Piperaquine single oral dose (Drug)
OZ439 100mg
100mg OZ439 single oral dose
干预措施: 100mg OZ439 single oral dose (Drug)
OZ439 100 mg + PQP 480mg
100mg OZ439 single oral dose + 480mg Piperaquine single oral dose
干预措施: 100mg OZ439 single oral dose (Drug)
OZ439 100 mg + PQP 480mg
100mg OZ439 single oral dose + 480mg Piperaquine single oral dose
干预措施: 480mg Piperaquine single oral dose (Drug)
OZ439 100 mg + PQP 1440mg
100mg OZ439 single oral dose + 1440mg Piperaquine single oral dose
干预措施: 100mg OZ439 single oral dose (Drug)
OZ439 100 mg + PQP 1440mg
100mg OZ439 single oral dose + 1440mg Piperaquine single oral dose
干预措施: 1440mg Piperaquine single oral dose (Drug)
OZ439 300mg
300mg OZ439 single oral dose
干预措施: 300 mg OZ439 single oral dose (Drug)
OZ439 300 mg + PQP 1440mg
300mg OZ439 single oral dose + 1440mg Piperaquine single oral dose
干预措施: 300 mg OZ439 single oral dose (Drug)
OZ439 300 mg + PQP 1440mg
300mg OZ439 single oral dose + 1440mg Piperaquine single oral dose
干预措施: 1440mg Piperaquine single oral dose (Drug)
OZ439 800mg
800mg OZ439 single oral dose
干预措施: 800 mg OZ439 single oral dose (Drug)
OZ439 800 mg + PQP 1440mg
800mg OZ439 single oral dose + 1440mg Piperaquine single oral dose
干预措施: 1440mg Piperaquine single oral dose (Drug)
OZ439 800 mg + PQP 1440mg
800mg OZ439 single oral dose + 1440mg Piperaquine single oral dose
干预措施: 800 mg OZ439 single oral dose (Drug)
Placebo
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Piperaquine Cmax
时间窗: Up to 1008 hours post-dose (Day 43)
Piperaquine Maximum concentration level
Piperaquine t1/2
时间窗: Up to 1008 hours post-dose (Day 43)
Piperaquine Elimination half-life (t1/2).
OZ439 AUC(0-168)
时间窗: Up to 168 hours post-dose
Area under the plasma concentration versus time curve to 168 hours post-dose.
Piperaquine AUC(0-168)
时间窗: Up to 1008 hours post-dose (Day 43)
Piperaquine area under the plasma concentration versus time curve to 168 hours post-dose
OZ439 Cmax
时间窗: Up to 168 hours post-dose
OZ439 Maximum concentration level
OZ439 t1/2
时间窗: Up to 168 hours post-dose
OZ439 Elimination half-life
次要结局
未报告次要终点