Development of Safer Drugs for Malaria in U.S. Troops, Civilian Personnel, and Travelers: Clinical Evaluation of Primaquine Enantiomer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Primary outcome: Plasma concentration of parent primaquine and carboyprimaquine following a single dose treatment with primaquine (racemate or enantiomers) not to exceed 45 mg
研究概览
简要总结
To investigate the comparative tolerability, metabolism and pharmacokinetics of individual enantiomers of PQ in healthy human volunteers. The specific aim is the comparative evaluation of the metabolism, pharmacokinetic behavior, and tolerability of the isomers of PQ (RPQ and SPQ and the racemic mixture RSPQ) in normal healthy human volunteers.
详细描述
The primary objective of this project is to investigate the comparative tolerability, metabolism and pharmacokinetics of individual enantiomers of PQ in healthy human volunteers.
The overall approach is as follows: in 36 healthy volunteers with documented normal G6PD activity, we will administer a single oral dose of RPQ, SPQ, or RSPQ. At various times after dosing, we will draw blood samples, in which we will record the plasma levels of the parent drugs, along with plasma and urinary metabolites. The comparative pharmacokinetics, tolerability and hematological effects of these two enantiomers and the racemate will be assessed.
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
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adults (18-60 years of age)
- •Informed consent
排除标准
- •Known history of liver, kidney or hematological disease;
- •known history of cardiac disease, arrhythmia, QT prolongation;
- •Autoimmune disorder;
- •Report of an active infection;
- •Evidence of G6PD deficiency
研究组 & 干预措施
Cohort 1 ( Primaquine Low Dose)
Interventions: Primaquine, R-Primaquine, S-Primaquine, SR Primaquine A single center, prospective, cross-over, randomized phase 1 trial. Thirty-six participants, enrolled into a two cohort pharmacokinetic study evaluating two dose levels of primaquine isomers.
Cohort 1 (Low Dose Level)- single dose of 15 mg of S-Primaquine and 15 mg of R-Primaquine compared to 30 mg RS-Primaquine over 24 hours. Participants will cross-over after a one week wash-out period.
干预措施: Primaquine, R-Primaquine, S-Primaquine, SR Primaquine (Drug)
Cohort 2 (Primaquine High Dose)
Interventions: Primaquine, R-Primaquine, S-Primaquine, SR Primaquine A single center, prospective, cross-over, randomized phase 1 trial. Thirty-six participants, enrolled into a two cohort pharmacokinetic study evaluating two dose levels of primaquine isomers.
Cohort 2 (High Dose Level)-single dose of 22.5 mg of S-Primaquine and 22.5 mg of R-Primaquine compared to 45 mg RS-Primaquine over 24 hours. Participants will cross-over among the treatment arms following a one week wash-out period between each.
干预措施: Primaquine, R-Primaquine, S-Primaquine, SR Primaquine (Drug)
结局指标
主要结局
Primary outcome: Plasma concentration of parent primaquine and carboyprimaquine following a single dose treatment with primaquine (racemate or enantiomers) not to exceed 45 mg
时间窗: between 0-24 Hours
This study would provide information on differential pharmacokinetics and metabolism of enantiomers of primaquine in normal human volunteers
次要结局
- Maximum concentration of selected metabolites primaquine (other than carboxyprimaquine) up to 24 hours after primaquine administration(between 0-24 hours)
- Area Under Curve (AUC) for primaquine up to 24 hours after the primaquine administration(between 0-24 hours)
- Maximum concentration of carboxyprimaquine, the major plasma metabolite of primaquine, up to 24 hours after primaquine administration(between 0-24 hours)
- Maximum concentration (Cmax) for primaquine up to 24 hours after the primaquine administration(between 0-24 hours)
- Area Under Curve (AUC) for carboxyprimaquine, the major plasma metabolite of primaquine, up to 24 hours after primaquine administration(between 0-24 hours)
- hemoglobin and methemoglobin levels in the blood after administration of primaquine(0-72 hours)
- Genotyping of Cytochrome P-450 (CYP)(day 0)