An Open-Label Pharmacokinetic Study to Evaluate the Bioavailability of Oral Primaquine and the Pharmacokinetics of Carboxyprimaquine in Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Area under the concentration-time curve (AUC0-∞) of primaquine and carboxyprimaquine
研究概览
简要总结
An open-label pharmacokinetic study. This study will enroll 20 healthy adult subjects (10 males and 10 females aged 18-60 years) at the Clinical Therapeutics Unit or inpatient ward, Faculty of Tropical Medicine, Mahidol University, Thailand.
The investigator propose to conduct a definitive bioavailability and pharmacokinetic study in healthy adult volunteers, both male and female, with normal CYP2D6 genotypes to assess oral primaquine bioavailability by the administration of intravenous and oral primaquine on different days and calculate the proportion of drug converted to its inactive metabolite, carboxyprimaquine, in order to estimate the proportion of its active metabolites. The intravenous injection of the known amount of carboxyprimaquine will allow the calculation of carboxyprimaquine's volume of distribution.
详细描述
This study will enroll 20 healthy adult subjects (10 males and 10 females aged 18-60 years).
Subjects will be admitted in the hospital and will receive 3 regimens of primaquine and its metabolite as described below. Every subject will have 1 screening and 3 admissions in the hospital.
Regimen 1: Primaquine 15 mg base orally once
Regimen 2: Primaquine 7.5 mg base in normal saline 500 mL infused over 30 minutes intravenously
Regimen 3: Carboxyprimaquine 7.93 mg base in normal saline 500 mL infused over 30 minutes intravenously
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Healthy as judged by a responsible physician with no significant abnormality identified on a medical evaluation including medical history and physical examination.
- •Male or female aged between 18 years to 60 years.
- •A female is eligible to enter and participate in this study if she is:
- •of non-childbearing potential including pre-menopausal females with documented (medical report verification) hysterectomy or double oophorectomy
- •postmenopausal defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum follicle stimulating hormone levels >40 milli-international units per milliliter (mIU/mL) or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy
- •of childbearing potential, has a negative serum pregnancy test at screening and urine pregnancy test prior to start the study drug in each period, and agrees to abstain from sexual intercourse or use effective contraceptive methods (e.g., intrauterine device, tubal ligation or female barrier method with spermicide except hormonal contraceptive) during the study until completion of the follow-up procedures
- •Willingness and ability to comply with the study protocol for the duration of the trial.
- •Subject is willing and able to give written informed consent for full participation in the study
排除标准
- •Females who are pregnant, trying to get pregnant, or are lactating.
- •Known to have any clinically significant disease or to have a clinically significant disease or disorder at this screening time
- •Donated more than 300 mL of whole blood within the previous 3 months
- •Non-smokers and non-tobacco user (i.e. having no past history of smoking and tobacco consuming for at least 3 months prior to study)
- •Consume alcohol or other alcohol containing products within 48 hours prior to the first dose of study drug and throughout the study
- •History or evidence of alcohol or substance abuse or dependence within 6 months before and throughout the study
- •Consume grapefruit and grapefruit containing products within 7 days prior to the first dose of study drug and throughout the study
- •Use of prescription drugs including but not limited to drugs with antimalarial activities and any drug contraindicated with the investigational drugs e.g. quinacrine, mefloquine or non-prescription drug, including, vitamins, herbal and dietary supplements (including St. John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication and for the duration of the trial including follow-up will be prohibited
- •Have taken part in research involving an investigational drug within the past 8 weeks
- •Use of medications known to have a potentially clinically significant interaction with primaquine
- •History of allergy to primaquine
- •Hb < 11 g/dL
- •Having malaria infection
- •Abnormal CYP2D6 genotype
- •Glucose-6-phosphate dehydrogenase (G6PD) deficiency by screening test
- •Aspartate aminotransferase (AST), alanine aminotransferase (ALT) > 1.5 times the upper limit of normal (ULN)
- •A serum creatinine (Scr) above the upper limit of normal (> 1.2 mg/dL) and estimated glomerular filtration rate (eGFR) < 70 mL/min/1.73 m2
- •Methaemoglobin (MetHb) level > 3% determined by oximetry
- •Positive for HIV-1, Hepatitis B or C virus infection
- •Subject who is likely to be unable to follow with the study procedures
研究组 & 干预措施
Regimen 1 (Oral primaquine), 2(IV primaquine phosphate), 3(IV carboxyprimaquine)
Regimen 1 (Oral primaquine): Primaquine 15 mg base orally once
Regimen 2 (IV primaquine phosphate): Primaquine 7.5 mg base in normal saline 500 mL infused over 30 minutes intravenously
Regimen 3 (IV carboxyprimaquine): Carboxyprimaquine 7.93 mg base in normal saline 500 mL infused over 30 minutes intravenously
干预措施: Regimen 1 (Oral primaquine) (Drug)
Regimen 1 (Oral primaquine), 2(IV primaquine phosphate), 3(IV carboxyprimaquine)
Regimen 1 (Oral primaquine): Primaquine 15 mg base orally once
Regimen 2 (IV primaquine phosphate): Primaquine 7.5 mg base in normal saline 500 mL infused over 30 minutes intravenously
Regimen 3 (IV carboxyprimaquine): Carboxyprimaquine 7.93 mg base in normal saline 500 mL infused over 30 minutes intravenously
干预措施: Regimen 2 (IV primaquine phosphate) (Drug)
Regimen 1 (Oral primaquine), 2(IV primaquine phosphate), 3(IV carboxyprimaquine)
Regimen 1 (Oral primaquine): Primaquine 15 mg base orally once
Regimen 2 (IV primaquine phosphate): Primaquine 7.5 mg base in normal saline 500 mL infused over 30 minutes intravenously
Regimen 3 (IV carboxyprimaquine): Carboxyprimaquine 7.93 mg base in normal saline 500 mL infused over 30 minutes intravenously
干预措施: Regimen 3 (IV carboxyprimaquine) (Drug)
结局指标
主要结局
Area under the concentration-time curve (AUC0-∞) of primaquine and carboxyprimaquine
时间窗: Approximately 3 months
Area under the concentration-time curve (AUC0-last) of primaquine and carboxyprimaquine
时间窗: Approximately 3 months
Area under the concentration-time curve (AUC0-∞) of oral and intravenous primaquine.
时间窗: Approximately 3 months
Area under the concentration-time curve (AUC0-last) of oral and intravenous primaquine.
时间窗: Approximately 3 months
Maximum concentration (Cmax) of primaquine and carboxyprimaquine
时间窗: Approximately 3 months
Elimination clearance (CL/F) of primaquine and carboxyprimaquine
时间窗: Approximately 3 months
Terminal elimination half-life (t1/2) of primaquine and carboxyprimaquine
时间窗: Approximately 3 months
Apparent volume of distribution (Vd) of primaquine and carboxyprimaquine
时间窗: Approximately 3 months
次要结局
- The characteristics of genetic polymorphisms of potential enzymes involved in drug metabolism in the case of unusual metabolizer(Approximately 3 months)