Metabolism and Pharmacokinetics of Primaquine Enantiomers in G6PD Deficient Human Volunteers Receiving a Five Day Dose Regimen
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Change in Methemoglobin concentration in blood from baseline
研究概览
简要总结
This study is a single center, prospective, cross-over phase 1 trial. Eighteen subjects will be enrolled in the study evaluating the metabolism, pharmacokinetic behavior and tolerability of primaquine enantiomers and placebo over the course of 5 days.
详细描述
Each subject will receive a 15 mg dose of one enantiomer (SPQ or RPQ or Placebo) daily for up to 5 days, with careful monitoring of hematological parameters before and after each dose. In addition to the general CMP14 safety criteria, any subject who displays a fractional hemoglobin drop of 15% below his/her baseline value, then drug administration will stop (e.g. for baseline Hgb of 14 g/dL, if there is at any point a decrease of 2.1 g/dL). Hematocrit will be similarly monitored, with proportional stop criteria. Elevation in total bilirubin to 2.0 mg/dL or greater will also be used as a stopping criterion. After stopping drug administration (5 days or whenever stop criteria are met), subjects will have a 3-week washout period, and the study repeated with the other enantiomer, and similarly with Placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •G6PD deficient, otherwise normal healthy adults aged 18 to 65
排除标准
- •Known history of liver, kidney or hematological disease (other than G6PD deficiency)
- •Known history of cardiac disease, non-sinus rhythm arrhythmia or QT prolongation
- •Autoimmune disorders
- •Report of an active infection
- •Subject is pregnant or breast-feeding, or is expecting to conceive during the study.
研究组 & 干预措施
RPQ (-) enantiomer
Cohort 1 will receive 15mg of RPQ every day for 5 days. Cohort 2 will receive 22.5 mg of RPQ every day for five days.
干预措施: RPQ (Drug)
SPQ (+) enantiomer
Cohort 1 will receive 15mg of SPQ every day for 5 days. Cohort 2 will receive 22.5 mg of SPQ every day for five days.
干预措施: SPQ (Drug)
Placebo
Cohort 1 will receive placebo capsules every day for 5 days. Cohort 2 will receive placebo capsules every day for five days.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Methemoglobin concentration in blood from baseline
时间窗: Days 0, 3, 5
Change in Methemoglobin concentration in blood from baseline (% hemoglobin)
次要结局
- Primaquine Orthoquinone Plasma concentration, ng/mL(Days 0, 3, 5)
- Change in Hemoglobin (g/dL) compared to baseline(Days 0, 3, 5)
- Primaquine Plasma Concentration, ng/mL(Days 0, 3, 5)
- Change in Hematocrit (%) compared to baseline(Days 0, 3, 5)
- Carboxy-Primaquine Plasma Contration, ng/mL(Days 0, 3, 5)
- Primaquine N-carbamoyl-glucuronide Plasma contration, ng/mL(Days 0, 3, 5)
- Change is AST (U/L) compared to baseline(Days 0, 3, 5)
- Change in ALT (U/L) compared to baseline(Days 0, 3, 5)
- Change in total Bilirubin (mg/dL) compared to baseline(Days 0, 3, 5)