Healthy Participants
Conditions
Keywords
Rivaroxaban, Bioequivalence, Pharmacokinetics, Fasting, Fed
Brief summary
This completed study compared how the body absorbed a single 2.5 mg dose of a test rivaroxaban tablet and the reference product (Xarelto) in healthy adults. The comparison was conducted separately under fasting and fed conditions. The study also evaluated the safety and tolerability of both products.
Detailed description
This was a single-center, randomized, open-label, single-dose, two-sequence, four-period, fully replicated crossover bioequivalence study. Healthy adults were enrolled independently into a fasting cohort (36 participants) or a fed cohort (28 participants). Within each cohort, participants were randomized 1:1 to the TRTR or RTRT treatment sequence. In each period, participants received one 2.5 mg rivaroxaban tablet with 240 mL of water; consecutive doses were separated by a washout interval of at least 7 days. Blood samples for pharmacokinetic assessment were collected before dosing and through 48 hours after dosing. Bioequivalence of the test and reference formulations was evaluated separately within the fasting and fed cohorts using Cmax, AUC0-t, and AUC0-infinity. The fasting and fed cohorts were not formally compared as a food-effect analysis.
Interventions
DRUGRivaroxaban 2.5 mg Test Tablet
One 2.5 mg rivaroxaban tablet manufactured by Qilu Pharmaceutical Co., Ltd. was administered orally with 240 mL of water in the assigned study periods.
DRUGRivaroxaban 2.5 mg Reference Tablet
One 2.5 mg Xarelto rivaroxaban tablet manufactured by Bayer Pharma AG was administered orally with 240 mL of water in the assigned study periods.
Sponsors
The Affiliated Hospital of Qingdao University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Intervention model description
Two independently enrolled cohorts (fasting and fed) were evaluated separately. Within each cohort, participants were randomized 1:1 to one of two fully replicated four-period sequences: TRTR or RTRT.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Healthy male or female participant aged 18 years or older. * Body weight at least 50 kg for males or at least 45 kg for females, with body mass index from 19.0 to 26.0 kg/m2, inclusive. * No plan for conception or gamete donation and willing to use effective contraception from screening (from 2 weeks before screening for females) until 6 months after the last dose. * Creatinine clearance greater than 80 mL/min. * Prothrombin time and activated partial thromboplastin time within the normal ranges. * Voluntarily provided written informed consent and understood the study procedures. * Able to comply with and complete the study requirements.
Exclusion criteria
* Specific allergy history, current allergic disease, allergic constitution, or known hypersensitivity to rivaroxaban, related compounds, or formulation components. * Clinically significant abnormal findings on physical examination, vital signs, electrocardiogram, or clinical laboratory testing. * Clinically significant neurologic, cardiovascular, renal, hepatic, gastrointestinal, respiratory, metabolic, musculoskeletal, or other disease that could affect drug absorption, distribution, metabolism, or excretion. * Active pathological bleeding, coagulation abnormality, or clinically relevant bleeding risk. * Positive test for human immunodeficiency virus antibody, hepatitis B surface antigen, hepatitis C antibody, or syphilis antibody. * Hereditary lactose or galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption. * Positive pregnancy test or breastfeeding. * History of drug abuse within 5 years or positive urine drug screen. * Hospitalization or surgery within 3 months before screening. * Regular alcohol intake exceeding 14 units per week within 3 months or positive breath alcohol test. * Smoking more than 5 cigarettes per day on average within 3 months. * Participation in another clinical study with study drug exposure within 3 months. * Blood donation or blood loss of at least 400 mL within 3 months, or donation of 2 therapeutic units of platelets within 1 month. * Use of prescription medication within 14 days, or nonprescription medication, herbal medicine, or health products within 7 days before dosing. * Use within 28 days before first dosing of drugs that strongly inhibit or induce P-glycoprotein or CYP3A4. * Consumption within 48 hours before dosing of grapefruit or related products, alcohol-, caffeine-, or xanthine-containing foods or beverages; strenuous exercise; or other factors potentially affecting pharmacokinetics. * Intolerance of venipuncture or history of needle or blood phobia. * Special dietary requirements or inability to comply with the standardized diet and study restrictions. * Any other condition that could prevent completion of the study or that the investigator considered unsuitable for participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration (Cmax) of Rivaroxaban | Predose through 48 hours after each dose | The maximum observed plasma concentration of rivaroxaban after administration of the test or reference formulation, reported in ng/mL. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) | Predose through 48 hours after each dose | Area under the rivaroxaban plasma concentration-time curve from time zero to the last quantifiable concentration, calculated after administration of the test or reference formulation and reported in h\*ng/mL. |
| Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-infinity) | Predose through 48 hours after each dose | Area under the rivaroxaban plasma concentration-time curve from time zero extrapolated to infinity, calculated after administration of the test or reference formulation and reported in h\*ng/mL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Maximum Plasma Concentration (Tmax) of Rivaroxaban | Predose through 48 hours after each dose | Time from dosing to the maximum observed plasma concentration of rivaroxaban after administration of the test or reference formulation, reported in hours. |
| Terminal Elimination Half-Life (t1/2) of Rivaroxaban | Predose through 48 hours after each dose | Terminal elimination half-life of rivaroxaban after administration of the test or reference formulation, reported in hours. |
| Terminal Elimination Rate Constant (Lambda z) of Rivaroxaban | Predose through 48 hours after each dose | Terminal elimination rate constant of rivaroxaban estimated from the terminal phase of the log-linear plasma concentration-time curve, reported as 1/hour. |
| Number of Participants With Adverse Events | From the first dose through the end-of-study safety follow-up, up to 40 days | Safety was assessed using adverse events, serious adverse events, adverse drug reactions, vital signs, physical examinations, clinical laboratory tests, coagulation tests, and 12-lead electrocardiograms. |
Countries
China
Outcome results
None listed