The study is conducted in healthy human volunteers to examine bioequivalence between two rivaroxaban formulations. Bioequivalence, rivaroxaban, generic rivaroxaban, pharmacokinetics, healthy volunteers
Conditions
Interventions
The subject who is assigned in Sequence 1 will receive REBLESS-20 (Test product) in Period 1 then Xarelto 20 mg (Reference product) in Period 2 while who is in Sequence 2 will receive Xarelto 20 mg (R
Experimental Drug,Active Comparator Drug
REBLESS-20,Xarelto 20 mg
Sponsors
Mankind Pharma Limited, India
Infinity Pharmaceutical Company Limited
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Inclusion criteria
Inclusion criteria: 1. Thai Male/Female must be 18-55 years of age, body weight more than 50.0 kg with body mass index (BMI) = 18.0-30.0 kg/m2, inclusive. 2. Must be in good health as determined by medical history, vital signs (blood pressure (systolic blood pressure not lower than 90 and not over 139 mmHg, diastolic blood pressure not lower than 60 and not over 89 mmHg), body temperature, pulse rate and respiratory rate) and physical examination or showing no clinically significant abnormalities in the opinion of Principal/Clinical Investigator or designated physicians 3. Screening ECG without clinically significant abnormalities in the opinion of Principal/Clinical Investigator or designated physicians 4. Screening visit laboratory values of blood test including hematology (CBC with differential), FBS, BUN, Cr and liver function test (AST, ALT, ALP and total bilirubin) must be within the normal range or showing no clinically significant abnormalities in the opinion of Principal/Clinical Investigator or designated physicians. 5. PT and aPTT should be within normal range or showing no clinically significant abnormalities in the opinion of Principal/Clinical Investigator or designated physicians. 6. Urinalysis results within normal limit or showing no clinically significant abnormalities in the opinion of Principal/Clinical Investigator or designated physicians 7. Must have serum HBsAg, anti-HCV and anti-HIV negative 8. Female subject must have serum beta-subunit of human chorionic gonadotropin (beta-hCG) within normal range of non-pregnant woman or showing no clinically significant abnormalities in the opinion of Principal/Clinical Investigator or designated physicians. 9. Female subject of childbearing potential or male subject agrees to use an acceptable birth control method from Screening Visit to Follow-up Visit. The acceptable birth control method is defined as a barrier method of contraception (including condoms, intrauterine device and diaphragm with spermicidal agent) or total abstinence from sexual intercourse from Screening Visit to Follow-up Visit. Hormonal contraceptives are not acceptable. 10. Female subject of non-childbearing potential (hysterectomy, both ovaries removed, surgically sterilized or postmenopausal (for at least 12 consecutive months of amenorrhea)) 11. Female subject must agree not to become pregnant for the entire participation period and must have a negative result for a urine pregnancy test before dose administration of each period. 12. Non-smoker (never smoked or no smoking within the previous 1 year as judged by medical history) 13. Refrain from using herbal medications, cannabis containing products, dietary supplements (e.g., St. John's Wort, ginkgo biloba, garlic supplements), vitamins, grapefruit or grapefruit juice, or pomelo within 14 days before the first dose administration of investigational product (Day 1). Subjects must agree to refrain from these items until the last collection time point of Period 2. 14. Subject must have ended any systemic medications or any medications that have any impact on gastrointestinal system at least 30 days prior to Day 1 or at least 7 times of elimination half-life prior to Day 1 and agree to continue their refraining throughout the follow-up period. 15. Subject must refrain from drinking caffeine and alcohol for at least 72 hours prior to Day 1 and agree to continue their refraining throughout the last collection time point of Period 2. 16. Have the ability
Exclusion criteria
Exclusion criteria: 1. Known hypersensitivity to rivaroxaban or any other similar class of drugs or its components 2. Past medical history of renal and hepatic insufficiency 3. Subject has a history of any illness that, in the opinion of Principal/Clinical Investigator or designated physicians, might confound the result of the study or pose an additional risk in administering investigational product to the subject. This may include but is not limited to: a history of relevant drug or food allergies; history of cardiovascular, gastrointestinal, central nervous system disease, renal and hepatic impairment; history or presence of clinically significant illness; or history of mental illness that may affect compliance with study requirements. 4. Have a history of significant hemorrhage within 6 months 5. Known of coagulation disorders (this may include but is not limited to hemophilia) or sensitive to common cause of bleeding 6. Have condition associated with an increase risk of bleeding. This may include but is not limited to: periodontitis, hemorrhoids, acute gastroenteritis and acute peptic ulcer. 7. CrCl less than 50 mL/min 8. Have history of drug abuse (in the opinion of Principal/Clinical Investigator or designated physicians, as judged by medical history) in the last 12 months 9. Have positive results of urine drug abuse test on opioids (Mor, MTD), cannabinoids (THC), Meth, Coc or MDMA at Screening Visit or before dose administration of each period 10. Alcohol abuse or excessive use (in the opinion of Principal/Clinical Investigator or designated physicians, as judged by medical history) in the last 12 months 11. Have positive result of alcohol breathing test at Screening Visit or before dose administration of each period 12. Female subject is pregnant or breast feeding. 13. Difficulties fasting or consuming standard high-fat, high-calorie meal or standard meals 14. Difficulties swallowing whole tablets 15. Donation or loss of whole blood: a. More than or equal to 50 mL and less than or equal to 499 mL within 30 days prior to Day 1 b. More than or equal to 500 mL within 56 days prior to Day 1 16. Participation in any investigational drug study within 30 days from Screening Visit (from the last Follow-up Visit of the previous study to Screening Visit of this study).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cmax, AUC0-t, AUC0-inf At pre-dose (duplicate) and 0.333, 0.667, 1.000, 1.333, 1.667, 2.000, 2.333, 2.667, 3.000, 3.500, 4.000, 4.500, 5.000, 5.500, 6.000, 8.000, 10.000, 12.000, 14.000, 24.000, and 36.000 hours post-dose Pharmacokinetic parameters will be obtained from rivaroxaban plasma concentrations using non-compartmental methods. | — |
Secondary
| Measure | Time frame |
|---|---|
| Tmax, Terminal elimination half-life, Terminal elimination rate constant and %Extrapolated AUC At pre-dose (duplicate) and 0.333, 0.667, 1.000, 1.333, 1.667, 2.000, 2.333, 2.667, 3.000, 3.500, 4.000, 4.500, 5.000, 5.500, 6.000, 8.000, 10.000, 12.000, 14.000, 24.000, and 36.000 hours post-dose Pharmacokinetic parameters will be obtained from rivaroxaban plasma concentrations using non-compartmental methods.,Safety of rivaroxaban in healthy Thai subjects under fed condition AEs will be collected from Day 1 after the first dose administration to the safety Follow-up Visit. Reported adverse events (AEs) | — |
Countries
Thailand
Contacts
Public ContactPinpilai Jutasompakorn
Faculty of Medicine Siriraj Hospital, Mahidol University
Outcome results
None listed