Rivaroxaban Hypericum Trial

Insel Gruppe AG, University Hospital Bern

Status and phase: Completed; Phase 1

Conditions: Drug Interaction Study

Treatments: Drug: St Johns Wort Extract; Drug: Rivaroxaban

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03796377

Studien-Nr. 3459

Details and patient eligibility

About

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.

Full 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.

Enrollment: 12 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

12 participants in 2 patient groups

Rivaroxaban

Other group

Description:

Single oral dose of 20 mg rivaroxaban

Treatment:

Drug: Rivaroxaban

Rivaroxaban after CYP- and P-gp induction

Other group

Description:

Single oral dose of 20 mg rivaroxaban after pretreatment with St. John's wort extract (Jarsin®) twice daily 450 mg po for 2 weeks.

Treatment:

Drug: Rivaroxaban

Drug: St Johns Wort Extract