Single-Dose, Fed Bioequivalence Study of MYLAN Rivaroxaban Tablets 20 mg (20 mg; Mylan) and Xarelto® 20 mg (20 mg; Bayer) in Healthy Adult Volunteers

Phase 1

• Conditions: Bioequivalence Study, Healthy, Thai Volunteers; Rivaroxaban &#44

• Registration Number: TCTR20201224002
• Lead Sponsor: International Bio Service Co.,Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-12-24
• Study Completion: 2021-04-23
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Pending (Not yet recruiting)
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

1.Healthy Thai male or female subjects between the ages of 18 to 55 years. Subject
must meet age requirements at the time of signing the initial informed consent and
at the dosing day in Period 1.
2.Body mass index between 18.0 to 30.0 kg/m2
3.Normal laboratory values, including vital signs and physical examination, for all
parameters in clinical laboratory tests at screening.
Any abnormalities from the normal or reference range will be carefully
considered clinically relevant by the physician as individual cases, documented
in study files prior to enrolling the subject in this study.
4.Non-smoker and non-consumer of nicotine containing products
Non-smoker or non-consumer of nicotine containing products means any
subject who has never smoked or stopped for at least 90 days.
5.Non-pregnant woman (negative pregnancy test) and not currently breast feeding.
6.Female subjects abstain from either hormonal methods of contraception (including
oral or transdermal contraceptives, injectable progesterone, progestin subdermal
implants, progesterone-releasing IUDs, postcoital contraceptive methods) or
hormone replacement therapy for at least 28 days prior to check-in in Period 1.
injectable contraceptives e.g. Depo-Provera® will be discontinued at least 6
months prior to check-in in Period 1. Subjects agree to use acceptable nonhormonal contraceptive methods such as condom, diaphragm, foams, jellies, or
abstinence for at least 14 days prior to check-in in Period 1 until 7 days after the
end of study in Period 2. Female subjects of non-childbearing potential must meet
at least one of the following criteria prior to check-in in Period 1:
ï‚· Postmenopausal for at least 1 year or
ï‚· Surgically sterile (bilateral tubal ligation, bilateral oophorectomy or
hysterectomy) at least 6 months
7.Male subjects who are willing or able to use effective contraceptive e.g. condom or
abstinence after check-in in Period 1 until 7 days after the end of study in Period 2.
8.Able to understand and voluntarily given written informed consent (signed and
dated) by the subject prior to participating in this study.
9.Adequate venous access in both arms for the collection of a number of samples
during the study

Exclusion Criteria

1.History of allergic reaction or hypersensitivity to rivaroxaban or to any excipients
of tablet
2.History or evidence of clinically significant renal, hepatic, gastrointestinal,
hematological (e.g. anemia), endocrine (e.g. hyper-/hypothyroid, diabetes),
pulmonary or respiratory (e.g. asthma), cardiovascular, psychiatric (e.g.
depression), neurologic (e.g. convulsant), allergic disease (including drug allergies,
but excluding untreated, asymptomatic, seasonal allergies at time of dosing) or any
significant ongoing chronic medical illness
3.Have high risk for coronavirus infection based on risk assessment questionnaire or
diagnosed as confirmed case of COVID-19
4.History or evidence of coagulation disorders e.g. von Willebrand's disease,
hemophilia
5.Active clinically significant bleeding e.g. intracranial or intracerebral bleeding,
gastrointestinal bleeding
6.History or evidence of disorders with increased bleeding risk e.g. periodontosis,
hemorrhoids, recent gastrointestinal bleeding or ulceration such as acute gastritis,
peptic ulcer, inflammatory bowel disease, gastroesophageal reflux disease, presence
of malignant neoplasms at high risk of bleeding, recent brain or spinal injury, recent
brain, spinal or ophthalmic surgery, oesophageal varices, oesophagitis,
arteriovenous malformations, vascular aneurysms, vascular retinopathy or major
intraspinal or intracerebral vascular abnormalities, bronchiectasis or history of
pulmonary bleeding.
7.History or evidence of galactose intolerance, the Lapp lactase deficiency or
glucose-galactose malabsorption
8.History of sensitivity to heparin or heparin-induced thrombocytopenia
9.Any condition possibly affecting drug absorption e.g. gastrectomy, enterectomy,
gastritis or duodenal or gastric ulceration other than appendectomy
10.History of preceding diarrhea within 24 hours prior to check-in in each period
11.History of febrile illness within 7 days prior to check-in in each period
12.History of problems with swallowing tablet or capsule
13.History or evidence of drug addict or investigation with urine sample shows a
positive test for drug of abuse (morphine, marijuana or methamphetamine)
14.Have sitting systolic blood pressure of less than 90 mmHg or more than 139 mmHg
and diastolic blood pressure of less than 60 mmHg or more than 89 mmHg on
screening day and check-in day. If abnormal blood pressure detects, the
measurement should be repeated two more times after take a rest for at least 5 mins
each. The last measurement value should be used to determine the subject‟s
eligibility.
15.12-lead ECG demonstrating QTc >450 msec, a QRS interval >120 msec or with an
abnormality considered clinically significant at screening. If QTc exceeds 450
msec, or QRS exceeds 120 msec, the ECG will be repeated two more times and the
average of the three QTc or QRS values will be used to determine the subject‟s
eligibility.
16.Investigation with blood sample shows positive test for HBsAg.
17.Abnormal liver function, ≥1.5 times of upper normal limit of reference range for
ALT, AST or bilirubin levels at screening laboratory test
18.Have renal creatinine clearance (Clcr) <50 mL/min based on serum creatinine
results, using glomerular filtration rate (GFR; Cockcroft-G

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Rivaroxaban plasma concentration 0-48 hrs Cmax, AUC0-tlast and AUC0-∞

Secondary Outcome Measures

Name	Time	Method
Rivaroxaban plasma concentration 0-48 hrs Tmax, t1/2, AUC0-tlast/AUC0-∞, AUC%extrapolate, λz and MRT ,Rivaroxaban plasma concentration 0-48 hrs Tmax, t1/2, AUC0-tlast/AUC0-∞, AUC%extrapolate, λz and MRT