Bioequivalence Study of Rivaroxaban 10 mg Film-coated Tablets

Bioequivalence Study of Rivaroxaban 10 mg Film-Coated Tablet Produced by PT Dexa Medica in Comparison With the Comparator Drug (Xarelto® 10 mg Film-Coated Tablet, Manufactured by Bayer AG, Germany, Imported by PT Bayer Indonesia, Indonesia) When Administered Under Fasting Condition in Healthy Subjects

This study was an open-label, randomized, single-dose, two-period, two-sequence, two-way crossover study under fasting conditions which included 28 healthy adult male and female subjects. The objective of this study was to compare whether the bioavailability of PT Dexa Medica's formulation of rivaroxaban 10 mg film-coated tablet is equivalent to that of the comparator drug (Xarelto® 10 mg Film-Coated Tablet, manufactured by Bayer AG, Germany, imported by PT Bayer Indonesia, Indonesia) when administered under fasting condition in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Rivaroxaban 10 mg film-coated tablet; Drug: Xarelto 10 mg film-coated tablet

Detailed Description

The objective of this study was to compare whether the bioavailability of PT Dexa Medica's formulation of rivaroxaban 10 mg film-coated tablet is equivalent to that of the comparator drug (Xarelto® 10 mg Film-Coated Tablet, manufactured by Bayer AG, Germany, imported by PT Bayer Indonesia, Indonesia) when administered under fasting condition in healthy subjects. This was an open-label, randomized, single-dose, two-period, two-sequence, two-way crossover study under fasting conditions which included 28 healthy adult male and female subjects. The participating subjects were required to have an 8 hours overnight fast and in the next morning (first day of period) were given orally the test drug (rivaroxaban 10 mg film-coated tablet produced by PT Dexa Medica) or the comparator drug (Xarelto® 10 mg Film-Coated Tablet, manufactured by Bayer AG, Germany, imported by PT Bayer Indonesia, Indonesia) with total 200 mL of water. The subject's oral cavity was checked thoroughly to confirm complete medication and fluid consumption after dosing. Blood samples were drawn before taking the drug (control), and at 0.33, 0.67, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.33, 3.67, 4.00, 4.33, 4.67, 5.00, 6.00, 8.00, 12.00, 24.00 and 36.00 hours after drug administration. These blood samples were used to investigate the pharmacokinetic parameters of rivaroxaban following single dose administration.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• Indonesia
  • Jakarta, Indonesia, 12430
    • PT Equilab International

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Able to participate, communicate well with the investigators and willing to provide written informed consent to participate in the study.
2. Healthy male and female subjects with absence of significant disease or clinically significant abnormal laboratory values on laboratory evaluation, medical history or physical examination during screening and could be considered healthy based on the evaluation.
3. Aged 18 - 55 years inclusive.
4. Non-smokers.
5. Body mass index within 18 to 25 kg/m2.

6. Vital signs (after 10 minutes rest) must be within the following ranges:

   • Systolic blood pressure: 100 - 129 mmHg
   • Diastolic blood pressure: 60 - 84 mmHg
   • Pulse rate: 60 - 90 bpm.
7. Willing to practice abstention or contraception during the study.
8. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) values should be within normal range.
9. Normal renal function with acceptable creatinine clearance (CrCl) >50 mL/min.

Exclusion Criteria:

1. History of allergy or hypersensitivity or contraindication to rivaroxaban or factor Xa inhibitors or allied drugs.
2. Pregnant or lactating female (urinary pregnancy test was applied to female subjects at screening and before taking the study drug).
3. Any major illness in the past 90 days or clinically significant ongoing chronic medical illness.
4. Presence of any clinically significant abnormal values during screening e.g. significant abnormality of liver function test (AST, ALT, alkaline phosphatase, total bilirubin, direct bilirubin ≥ 1.5 ULN), renal function test (serum creatinine concentration > 1.4 mg/dL and ureum ≥ 1.5 ULN), etc.
5. Patient with significant liver disease (severe hepatic impairment/Child Pugh C).
6. Positive Hepatitis B surface antigen (HBsAg), anti-HCV, or anti-HIV.
7. Positive result for COVID-19 rapid antigen test (this criteria only applied if the study conduct during pandemic condition).
8. Clinically significant hematology abnormalities.
9. Clinically significant electrocardiogram (ECG) abnormalities.
10. Any surgical or medical condition (present or history) which might significantly alter the absorption, distribution, metabolism or excretion of the study drug, e.g. gastrointestinal disease including gastric or duodenal ulcers or history of gastric surgery.
11. Past history of anaphylaxis or angioedema.
12. History of drug or alcohol abuse within 12 months prior to screening for this study.
13. Participation in any clinical trial within the past 90 days calculated from the last visit until this study's first dosing day.
14. History of any bleeding or coagulative disorders.
15. History of significant head or spinal cord injury or recent surgery on the brain, spinal cord or eyes.
16. Presence of difficulty in accessibility of veins in left or right arm.
17. A donation or significant blood loss within 90 days before this study's first dosing day.
18. Intake of any prescription, non-prescription drug (including hormonal contraception), food supplements or herbal medicines within 21 days of this study's first dosing day.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test Rivaroxaban 10 mg PT Dexa Medica; Rivaroxaban 10 mg Film-coated Tablet, produced by PT Dexa Medica, Indonesia	Drug: Rivaroxaban 10 mg film-coated tablet; One tablet of the test drug was given orally after an overnight fast.
Active Comparator: Reference Xarelto 10 mg Bayer; Xarelto 10 mg Film-Coated Tablet, manufactured by Bayer AG, Germany, imported by PT Bayer Indonesia, Indonesia	Drug: Xarelto 10 mg film-coated tablet; One tablet of the reference drug was given orally after an overnight fast.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum plasma concentration	36 hours
AUC(0-t)	Area under the plasma concentration-time curve to the last observer quantifiable concentration at time t	36 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC(0-inf)	Area under the plasma concentration-time curve extrapolated to infinitive time	36 hours
T1/2	Plasma half-life	36 hours
Tmax	Time taken to reach maximum observed plasma concentration	36 hours

Collaborators and Investigators

• Sponsor: Dexa Medica Group
• Collaborators: PT Equilab International

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2023
• Primary Completion (Actual): June 16, 2023
• Study Completion (Actual): August 29, 2023

Study Registration Dates

• First Submitted: August 14, 2024
• First Submitted That Met QC Criteria: August 14, 2024
• First Posted (Actual): August 16, 2024

Study Record Updates

• Last Update Posted (Actual): August 16, 2024
• Last Update Submitted That Met QC Criteria: August 14, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• 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: BE. 786/EQL/2023

Drug and device information, study documents

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