Pharmacokinetics and Bioequivalence of Rivaroxaban Tablet in Healthy Chinese Volunteers

Pharmacokinetics and Bioequivalence of Generic and Branded Rivaroxaban Tablet in Healthy Chinese Volunteers Under Fasting and Fed Conditions

The study was designed as a single-site, randomized, open-label, four-period complete and replicate crossover. A single oral dose of 20 mg rivaroxaban tablet (test) and Xarelto®(reference) was given to the 72 healthy Chinese adult volunteers, with 36 in a fasting state and 36 receiving a high-fat diet.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: Rivaroxaban 20 MG Oral Tablet; Drug: Rivaroxaban 20 MG Oral Tablet [Xarelto]

Detailed Description

Subjects were randomized into two treatment sequence groups: Sequence 1 = TRTR and Sequence 2 = RTRT, and each study period was separated by a 7 days washout period. After an overnight fast for at least 10 h, the subjects received a single oral dose of the R or T formulation of rivaroxaban tablets (20 mg) with 240 mL of water in a seated position. A total of 19 blood samples were collected at 0 (within 60 min prior to dosing) and 0.25,0.5, 1.0, 1.5, 2.0, 2.5,3.0,3.5, 4.0, 4.5,5.0, 5.5,6.0, 8.0, 12.0, 24.0, 36.0 ,and 48.0 hours after dosing.Blood samples were collected in a vacuum blood tube containing sodium heparin, gently mixed, and stored on ice-water mixture until sample processing and then centrifuged at 2000g at 2-8°C for 10 min.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shandong
    • Qingdao, Shandong, China, 266003
      • Phase I Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male or female aged 18 and above.
• The body mass index is in the range of 19.0-26.0 kg/m2 (including the critical value). The weight of male is not less than 50.0 kg, and that of female is not less than 45.0 kg.
• The following examination show that the indicators are normal or abnormal without clinical significance. The examination including: Vital signs, physical examination, blood routine, blood biochemistry, urinalysis, pregnancy test for female, serological tests for hepatitis B virus, hepatitis C virus, human immunodeficiency virus (HIV), and syphilis virus, 12 lead ECG, breath test for alcohol, drug abuse test.
• The subjects have no family planning within 3 months and could select contraceptive method.Before the study, all subjects
• Before the study, all subjects have been informed of the study's purpose, protocal, benefits, and risks, and signed the informed consent voluntarily.

Exclusion Criteria:

• Being allergy to the study medications, smoking, alcohol abuse.
• Participation in another clinical trial within 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Rivaroxaban 20 MG Oral Tablet [Xarelto]; rivaroxaban oral tablet [Xarelto] at a single oral dose of 20 mg	Drug: Rivaroxaban 20 MG Oral Tablet; The subjects randomly received single oral administration of Rivaroxaban 20 MG Oral Tablet.
EXPERIMENTAL: Rivaroxaban 20 MG Oral Tablet; rivaroxaban oral tablet at a single oral dose of 20 mg	Drug: Rivaroxaban 20 MG Oral Tablet [Xarelto]; The subjects randomly received single oral administration of Rivaroxaban 20 MG Oral Tablet [Xarelto].

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Plasma Concentration (Cmax)	Evaluation of Peak Plasma Concentration (Cmax)	94 days
Area under the plasma concentration versus time curve (AUC)0-t	Evaluation of Area under the plasma concentration versus time curve (AUC)0-t	94 days
Area under the plasma concentration versus time curve (AUC)0-∞	Evaluation of Area under the plasma concentration versus time curve (AUC)0-∞	94 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events	Collection of adverse events	94 days
Incidence of abnormal blood pressure	Monitor the blood pressure	94 days
Incidence of abnormal temperature	Monitor the temperature	94 days
Incidence of abnormal pulse	Monitor the pulse	94 days
Incidence of abnormal electrocardiogram waveform	Electrocardiogram inspection	94 days

Collaborators and Investigators

• Sponsor: The Affiliated Hospital of Qingdao University
• Investigators: Principal Investigator: yu Cao, the study director of phase I clinical research center

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 4, 2019
• Primary Completion (ACTUAL): September 5, 2019
• Study Completion (ACTUAL): September 20, 2019

Study Registration Dates

• First Submitted: June 3, 2020
• First Submitted That Met QC Criteria: June 8, 2020
• First Posted (ACTUAL): June 11, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 11, 2020
• Last Update Submitted That Met QC Criteria: June 8, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: pharmacokinetics; bioequivalence; rivaroxaban
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban
• Other Study ID Numbers: QL-YK4-012-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All the technical achievements and outcomes of this trial are owned by Qilu Pharmaceutical Co., Ltd. and the research center. The research center can not publish any academic papers without the consent of the sponsor

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No