Bioequivalence study of rivaroxaban 20 mg film-coated tablet produced by PT Dexa Medica in comparison with the comparator drug (Xarelto® 20 mg Film-Coated Tablet, manufactured by Bayer AG, Germany, imported by PT Bayer Indonesia, Indonesia) when administered under fed condition in healthy subjects.


INA-MWZQTNN
07-12-2023
29-11-2023
No
Bioequivalence study of rivaroxaban 20 mg film-coated tablet produced by PT Dexa Medica in comparison with the comparator drug (Xarelto® 20 mg Film-Coated Tablet, manufactured by Bayer AG, Germany, imported by PT Bayer Indonesia, Indonesia) when administered under fed condition in healthy subjects.
Bioequivalence study of rivaroxaban 20 mg film-coated tablet produced by PT Dexa Medica in comparison with the comparator drug (Xarelto® 20 mg Film-Coated Tablet, manufactured by Bayer AG, Germany, imported by PT Bayer Indonesia, Indonesia) when administered under fed condition in healthy subjects.
 
PT Dexa Medica
PT Dexa Medica
PT Equilab International
 
Danang Agung Yunaidi, MD
Jakarta
Indonesia
Natalia Denda Wijaya
natalia.wijaya@equilab-int.com
Kartika Widyanty
Jl. Boulevard Bintaro Blok B7/B1 No. 05 Bintaro Jaya Sektor 7 Tangerang Selatan 15224 – INDONESIA.
Tangerang Selatan
Indonesia
15224
Monica Mutiara Anindita
monica.anindita@dexa-medica.com
085290819937
Kartika Widyanty
Jl. Boulevard Bintaro Blok B7/B1 No. 05 Bintaro Jaya Sektor 7 Tangerang Selatan 15224 – INDONESIA.
Tangerang Selatan
Indonesia
15224
Monica Mutiara Anindita
kartika.widyanty@dexa-medica.com
 
KET-295/UN2.F1/ETIK/PPM.00.02/2023
The Ethics Committee of Faculty of Medicine, University of Indonesia – Cipto Mangunkusumo Hospital.
13-03-2023
Gedung Fakultas Kedokteran UI Jalan Salemba Raya No.6, Jakarta Phone : 0213912477 Email : humas@fk.ui.ac.id
RG.01.02.321.04.23.01654/UB
 
Indonesia
PT Equilab International
Complete
06-07-2023
00028 -
26
18-07-2023
 
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.
Bioequivalence study
Interventional
Bioequivalence study
Test drug: Rivaroxaban 20 mg Film-Coated Tablet (produced by PT Dexa Medica, Indonesia) Reference drug: Xarelto® 20 mg Film-Coated Tablet (produced by Bayer AG, Germany, imported by PT Bayer Indonesia, Indonesia)
The subjects blood samples will be taken at a certain time. Drug administration, drink and meal for subjects, and subject activities will be standardized during study period.
Crossover
 
Male, Female
18 years
55 years
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 the 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 range: a) Systolic blood pressure : 100 - 129 mmHg. b) Diastolic blood pressure : 60 - 84 mmHg. c) 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.
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.
 
To compare whether the bioavailability of PT Dexa Medica’s formulation of rivaroxaban 20 mg film-coated tablet is equivalent to that of the comparator drug (Xarelto® 20 mg Film-Coated Tablet, manufactured by Bayer AG, Germany, imported by PT Bayer Indonesia, Indonesia) when administered under fed condition in healthy subjects.
The bioequivalence of the two products was concluded based on the 90% confidence intervals of the test/comparator geometric mean ratios of Rivaroxaban AUC0-t and Cmax which were within the range of 80.00 - 125.00%.
The subjects blood samples will be taken at a certain time. Drug administration, drink and meal for subjects, and subject activities will be standardized during study period.
 
It was concluded that the rivaroxaban 20 mg film-coated tablet produced by PT Dexa Medica as bioequivalent to the comparator drug (Xarelto® 20 mg Film-Coated Tablet, manufactured by Bayer AG, Germany, imported by PT Bayer Indonesia, Indonesia) in healthy subjects, based on the findings that the 90% confidence intervals for AUC0-t and Cmax were within the range of 80.00 - 125.00%.
10-10-2023