BE Study of Two Formulations of Rivaroxaban 2.5 mg in Healthy Subjects

An Open-label, Randomized, 2-sequence, 2-period, Fasted, Single Dose, Oral Administration, Crossover Study to Evaluate the Bioequivalence of YHP1807 Tablets 2.5 mg and YHR1901 Tablets 2.5 mg in Healthy Volunteers

The objective of this study was to compare the pharmacokinetic profiles and bioequivalence of rivaroxaban after a single oral dose of rivaroxaban 2.5 mg tablet in healthy Korean subjects.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: YHP1807 Tab. 2.5mg; Drug: YHR1901 Tab. 2.5mg

Detailed Description

This study was a randomized, open-label, single-dose, two-period, crossover study which included 34 healthy adult male and female subjects under fasting conditions. A single dose of experimental drug or comparator was administered in each of the two study periods (separated by a washout period of 1 week). Serial blood samples were collected up to 36 hours post-dose. Plasma drug concentrations were measured by liquid chromatography/tandem mass spectrometry (LC-MS/MS). Pharmacokinetic parameters, including maximum plasma concentration (Cmax) and area under the plasma concentration versus time curve from dosing to the last measurable concentration (AUCt), were determined by non-compartmental analysis. The geometric mean ratios and associated 90% confidence intervals (CIs) of log-transformed Cmax and AUCt were calculated to evaluate pharmacokinetic equivalence.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Jeollabuk-do
    • Jeonju, Jeollabuk-do, Korea, Republic of, 54907
      • Jeonbuk National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male/female aged 19 to 55 with body mass index(BMI) between 18.5 and 30kg/m2
• Acceptable medical history, physical examination, laboratory tests and EKG, during screening
• Subjects who has signed a written informed consent voluntarily

Exclusion Criteria:

• History of clinically significant medical history or current disease

• Hypotension (SBP ≤ 90 mmHg or DBP ≤ 60 mmHg) or hypertension (SBP

  ≥ 140 mmHg or DBP ≥ 90 mmHg).

• AST(SGOT) or/and ALT(SGPT) > 1.5 times of normal upper limit
• Total bilirubin > 2.0 mg/dl
• Volunteers considered not eligible for the clinical trial by the investigator
• Administration of other investigational products within 6 month prior to the first dosing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group1; 17 subjects, Cross-over, Single dose of comparator on day1, YHP1807 on day8	Drug: YHP1807 Tab. 2.5mg; Rivaroxaban 2.5mg; Other Names: Experimental; Drug: YHR1901 Tab. 2.5mg; Rivaroxaban 2.5mg; Other Names: Active comparator
Active Comparator: Group2; 17 subjects, Cross-over, Single dose of YHP1807 on day1, comparator on day8	Drug: YHP1807 Tab. 2.5mg; Rivaroxaban 2.5mg; Other Names: Experimental; Drug: YHR1901 Tab. 2.5mg; Rivaroxaban 2.5mg; Other Names: Active comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUCt	AUCt of Rivaroxaban	0-36 hours
Cmax	Cmax of Rivaroxaban	0-36 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUCinf	AUCinf of Rivaroxaban	0-36 hours
Tmax	Tmax of Rivaroxaban	0-36 hours
t1/2	t1/2 of Rivaroxaban	0-36 hours

Collaborators and Investigators

• Sponsor: Yuhan Corporation

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2020
• Primary Completion (Actual): February 14, 2020
• Study Completion (Actual): February 14, 2020

Study Registration Dates

• First Submitted: June 9, 2022
• First Submitted That Met QC Criteria: June 9, 2022
• First Posted (Actual): June 14, 2022

Study Record Updates

• Last Update Posted (Actual): June 16, 2022
• Last Update Submitted That Met QC Criteria: June 13, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: YHP1807-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

De-identified individual participant data (including data dictionaries) that underline the results reported in study-related publications will be made available during the period beginning 1 year and ending 5 years after all trial primary and secondary endpoints were assessed. Only requests from researchers who provide a methodologically sound proposal will be reviewed and approved by the sponsor. The analysis type should be in accordance with aims in the proposal approved by the sponsor. Proposals should be directed to ejsong@yuhan.co.kr.

A summary of the study results will be posted in the publicly accessible database (i.e. clinicaltrials.gov).

• IPD Sharing Time Frame: Beginning 1 year and ending 5 years after all trial endpoints were assessed
• IPD Sharing Access Criteria: Only requests from researchers who provide a methodologically sound proposal will be reviewed and approved by the sponsor. The analysis type should be in accordance with aims in the proposal approved by the sponsor. Proposals should be directed to ejsong@yuhan.co.kr.
• IPD Sharing Supporting Information Type: Study Protocol; Clinical Study Report (CSR)

Drug and device information, study documents

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