Rivaroxaban Hypericum Trial
- Conditions
- Drug Interaction Study
- Interventions
- Drug: St Johns Wort Extract
- Registration Number
- NCT03796377
- Lead Sponsor
- Insel Gruppe AG, University Hospital Bern
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 12
- 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
- Known allergic reaction to any excipient of the drug formulations
- Known photosensitivity
- Smoking
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Rivaroxaban Rivaroxaban Single oral dose of 20 mg rivaroxaban Rivaroxaban after CYP- and P-gp induction St Johns Wort Extract Single oral dose of 20 mg rivaroxaban after pretreatment with St. John's wort extract (Jarsin®) twice daily 450 mg po for 2 weeks. Rivaroxaban after CYP- and P-gp induction Rivaroxaban Single oral dose of 20 mg rivaroxaban after pretreatment with St. John's wort extract (Jarsin®) twice daily 450 mg po for 2 weeks.
- Primary Outcome Measures
Name Time Method Pharmacokinetic outcome measures: area under the curve (AUC). 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. 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 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)).
- Secondary Outcome Measures
Name Time Method 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 Time to reach maximal concentration of rivaroxaban
Phenotyping metrics: AUC fexofenadine Time points used for analysis: Before dosing and 0.5, 2, 3, 6 h after administration Estimated AUC of fexofenadine
Phenotyping metrics: Single point metabolic ratios midazolam Time points used for analysis: Before dosing and 0.5, 2, 3, 6 h after administration Single point metabolic ratios of midazolam and 1'-hydroxymidazolam
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 Plasma elimination half-life of rivaroxaban
Phenotyping metrics: AUC ratios midazolam Time points used for analysis: Before dosing and 0.5, 2, 3, 6 h after administration AUC ratios of midazolam and 1'-hydroxymidazolam
Trial Locations
- Locations (1)
Inselspital
🇨🇭Bern, Switzerland