Effects of Hypericum Perforatum (St. John's Wort) on the Pharmacokinetics and Pharmacodynamics of Rivaroxaban in Humans
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Pharmacokinetic outcome measures: area under the curve (AUC).
研究概览
简要总结
Single-center, open-label, sequential treatment study to investigate the influence of the combined P-glycoprotein and CYP3A4 inducer hypericum perforatum on the pharmacokinetics and pharmacodynamics of rivaroxaban in healthy volunteers.
详细描述
Each session (one with and one without preceding CYP induction) will start with phenotyping using 25 mg fexofenadine orally for P-gp phenotyping and 2 mg midazolam orally for cytochrome P450 (CYP) 3A4 phenotyping. After a washout period of 5 days, subjects will receive a single oral dose of 20 mg rivaroxaban, a dose currently approved for human use in clinical routine. The same procedure will be repeated after pretreatment with St. John's wort extract (Jarsin®) twice daily 450 mg po (dose usually used in clinical routine) for 2 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Men or women, age between 18 and 45 years (inclusive) at screening
- •BMI between 18 and 28 kg/m2 (inclusive) at screening
- •No clinically significant findings on the physical examination at screening
- •Hematology and clinical chemistry results not deviating from the normal range to a clinically relevant extent at screening
- •Ability to communicate well with the investigator and to understand and comply with the requirements of the study
- •Women of child-bearing age: willingness of using a double barrier contraception method during the study, i.e. a hormonal method (oral contraceptive, intrauterine device) in combination with a mechanical barrier (e.g. condom, diaphragm)
- •Signed informed consent
排除标准
- •Known allergic reaction to any excipient of the drug formulations
- •Known photosensitivity
- •History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to screening
- •Loss of ≥ 250 ml of blood within 3 months prior to screening, including blood donation
- •Treatment with an investigational drug within 30 days prior to screening
- •Previous treatment with any prescribed or over-the-counter medications (including herbal medicines such as St. John's wort) within 2 weeks prior to screening
- •Pregnant (positive results from urine drug screen at screening) or lactating women
- •History or clinical evidence of any disease (e.g. gastrointestinal tract disease) and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism or excretion of the study drugs, or which might increase the risk for toxicity
- •Legal incapacity or limited legal capacity at screening
- •Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol
研究组 & 干预措施
Rivaroxaban
Single oral dose of 20 mg rivaroxaban
干预措施: Rivaroxaban (Drug)
Rivaroxaban after CYP- and P-gp induction
Single oral dose of 20 mg rivaroxaban after pretreatment with St. John's wort extract (Jarsin®) twice daily 450 mg po for 2 weeks.
干预措施: St Johns Wort Extract (Drug)
Rivaroxaban after CYP- and P-gp induction
Single oral dose of 20 mg rivaroxaban after pretreatment with St. John's wort extract (Jarsin®) twice daily 450 mg po for 2 weeks.
干预措施: Rivaroxaban (Drug)
结局指标
主要结局
Pharmacokinetic outcome measures: area under the curve (AUC).
时间窗: AUC will be calculated from the concentration-time plot (time points included: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 hours (post-dose) during both sessions)
Effect of pretreatment with hypericum perforatum on geometric mean AUC.
Pharmacokinetic outcome measures: maximal concentration of rivaroxaban.
时间窗: Will be obtained from the individual plasma concentration data (time points included: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 hours (post-dose) during both sessions)
Effect of pretreatment with hypericum perforatum on maximal concentration of rivaroxaban.
Pharmacodynamic outcome measures: Factor Xa activity
时间窗: Time points used for analysis: pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36, and 48 hours (post-dose) during both sessions
Displayed as maximal effect (Emax) and parametrized by calculating the area under the time-effect curves (AUEC)).
次要结局
- Pharmacokinetic parameters: Time to reach maximal concentration(Time points used for analysis: 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 hours (post-dose) during both sessions)
- Phenotyping metrics: AUC fexofenadine(Time points used for analysis: Before dosing and 0.5, 2, 3, 6 h after administration)
- Phenotyping metrics: Single point metabolic ratios midazolam(Time points used for analysis: Before dosing and 0.5, 2, 3, 6 h after administration)
- Pharmacokinetic parameters: Plasma elimination half-life(Time points used for analysis: 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 hours (post-dose) during both sessions)
- Phenotyping metrics: AUC ratios midazolam(Time points used for analysis: Before dosing and 0.5, 2, 3, 6 h after administration)