Pharmacokinetics and pharmacodynamics of rivaroxaban Not Applicable
Conditions
Interventions
Screening of subject (Days -7 to -1)
Trial Phase 1: participants hospitalized for days 0 - 3: one single dose of rivaroxaban on day 1, pharmacokinetic and pharmacodynamic measures from 30 min pre-dose to 48 hours post-dose, discharge fro
days 4 - 6 outpatient without treatment.
Trial Phase 2: participants hospitalized for days 4 - 7: one dose of EGb 761 and one single dose of rivaroxaban on day 8
EGb 761 intake from day 8 - 15
pharmacokinetic and pharmacodynamic measures from 30 min pre-dose rivaroxaban to 48 hours post-dose rivaroxaban, discharge from hospital on day 10
days 11 - 13 outpatient with EGb 761 intake. Trial phase
pharmacokinetic and pharmacodynamic measures from 30 min pre-dose rivaroxaban to 48 hours post-dose rivaroxaban, discharge from hospital and end of trial on day 17.
Rivaroxaban concen
Sponsors
Dr. W. Schwabe GmbH & Co. KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female volunteers 2. Age at least (=) 18 years at screening 3. Caucasian 4. Body mass index (BMI) 18.0 – 29.9 kg/m² (included) 5. Healthy on the basis of specified criteria evaluated at the screening visit (physical examination, ECG, vital signs, safety and coagulation laboratory) 6. Signed informed consent in accordance with the legal requirements
Exclusion criteria
Exclusion criteria: 1. Participation in a further clinical trial at the same time or within the past 3 months before screening 2. Female subjects: pregnancy or lactation 3. Female subjects of childbearing potential not using adequate contraception 4. Positive pregnancy test at screening or Day -1 5. Gastrointestinal disorders with uncertain absorption of orally administered drugs (e.g., partial or total gastrectomy, enterectomy, inflammatory bowel disease, celiac disease, symptomatic lactose intolerance, other disorders associated with chronic diarrhoea) 6. Hypersensitivity to any of the IMPs or components thereof 7. Hereditary galactose intolerance, lactase deficiency, or glucose-galactose malabsorption 8. Any condition which constitutes a contra-indication for treatment with EGb 761® (e.g., high bleeding risk, regular intake of coagulation-inhibiting drugs, epilepsy or history of seizures) 9. Any condition which constitutes a contra-indication for treatment with rivaroxaban (e.g., acute, relevant bleeding, lesions, clinical situations with increased risk of severe bleeding) 10. Presence of any possibly relevant active co-morbidity (including conditions that might affect absorption, distribution and elimination of the investigational compounds; acute or chronic infections) 11. Use of any concomitant medication within 2 weeks or less than 5× t½ of the respective medication before first administration 12. Presence of any possibly confounding clinical laboratory at screening including but not confined to abnormal values for complete blood count, coagulation, serology and clinical chemistry, if assessed as clinically relevant by the investigator. Note: As neither rivaroxaban nor EGb 761® are hepatotoxic, slight elevations are acceptable for hepatic parameters if there is no indication of apparent disease: 10% above upper limit of normal (ULN) for alanine aminotransferase (ALT), 20% above ULN for aspartate aminotransferase (AST) or bilirubin (except in case of Gilbert’s disease: elevated bilirubin is not relevant). Slight elevation (10%) acceptable for renal parameters (except for creatinine) if there is no indication of apparent disease [Breithaupt-Grögler et al., 2017] 13. Depiction of bleeding tendencies defined by the presence of pathological coagulation parameters performed at screening, including but not confined to prothrombin time (Quick,), von Willebrand factor (vWF), platelet function assay PFA-100 and factor XIII 14. Positive test for human immunodeficiency virus (HIV) antibodies, hepatitis B-virus surface antigen (HBsAg), or anti-hepatitis C virus antibodies (anti-HCV) at screening 15. Positive immunological testing on occult blood in faeces at screening 16. Positive test for blood in urine at screening (except due to menses in female subjects) 17. Elevated blood pressure (confirmed by second measurement): Systolic blood pressure (SBP) = 140 mmHg or diastolic blood pressure (DBP) = 90 mmHg at screening 18. Pulse rate 90 bpm at rest at screening. 19. Relevant abnormality in 12-lead ECG at screening including, but not confined to prolonged HR-controlled QTc (normal ranges: QTcB = 450 ms [male s
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Pharmacokinetic outcome variables: 1.1. AUC0 8 and Cmax of rivaroxaban (primary PK endpoints) based on plasma concentrations of rivaroxaban measured using high-pressure liquid chromatography (HPLC) coupled to tandem mass spectrometry at sampling timepoints: predose to rivaroxaban intake (0 h), 0,5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h and 24 h after intake 1.2. AUC0 t, AUC0 tz, %AUCtz 8, tmax, MRT, t1/2?z of rivaroxaban based on plasma concentrations of rivaroxaban measured using high-pressure liquid chromatography (HPLC) coupled to tandem mass spectrometry at sampling timepoints: predose to rivaroxaban intake (0 h), 0,5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h and 24 h after intake 2. Pharmacodynamic outcome variables: Emax and AUEC of anti-Factor Xa activity, based on plasma concentrations of anti-Factor Xa, measured using the standard method at the laboratory (automated chromogenic test method) at sampling timepoints: predose to rivaroxaban intake (0 h), 0,5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h and 24 h after intake 3. Safety outcome variables: 3.1. Adverse events (AEs) measured by interview personally or by phone call every day from day -7 to day 17 including follow-up if an AE is not finished on day 17 3.2. Safety lab panel: clinical chemistry, haematology, urinalysis, pregnancy test, alcohol breath test, urine drug screen, SARS-CoV-2 viral DNA test on days -2, -1, 8, 15 and 17 3.3. Vital signs: body temperature, blood pressure in supine position on days -2, -1, 1 - 3, 8 – 10, 15 – 17 3.4. ECG: standard 12-lead ECG after 5 min in supine position on days -2, -1, 8, 15 and 17 3.5. Physical examination: physical inspection of general status, nutritional condition, head/neck, heart/circulatory system, lungs/respiratory tract, abdomen/gastrointestinal system, kidneys, urogenital tract, musculoskeletal system | — |
Secondary
| Measure | Time frame |
|---|---|
| There are no secondary outcome measures | — |
Countries
Germany
Contacts
Public ContactSusanne Kraft
Outcome results
None listed