Bioequivalence study in healthy Thai male volunteers Edoxaban 60 mg Film-coated Tablets and Reference Product (Lixiana) in Healthy Thai Volunteers under Fasting Conditions
Conditions
Interventions
Each tablet contains 60 mg edoxaban. (Test product),Each film-coated tablet contains 60 mg edoxaban (as tosilate).(Reference product)
Experimental Drug,Active Comparator Drug
Generic edoxaban 60 mg film-coated tablet,Edoxaban 60 mg film-coated tablet, Lixiana
Sponsors
International Bio Service Co., Ltd.
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Inclusion criteria
Inclusion criteria: 1.Healthy Thai male or female subjects between the ages of 18 to 55 years. 2.Body mass index between 18.5 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-pregnant woman (negative pregnancy test) and not currently breast feeding. 5.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 non-hormonal contraceptive methods such as condom, diaphragm, foams, jellies, or abstinence for at least 14 days prior to check-in in Period 1 until 10 days after the end of study in Period 3. Female subjects of non-childbearing potential must meet at least one of the following criteria prior to check-in in Period 1: -Postmenopausal for at least 1 year or -Surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy) at least 6 months. 6.Male subjects who are willing or able to use effective contraceptive e.g. condom or abstinence after check-in in Period 1 until 10 days after the end of study in Period 3. 7.Have voluntarily given written informed consent (signed and dated) by the subject prior to participating in this study.
Exclusion criteria
Exclusion criteria: 1.History of allergic reaction or hypersensitivity to edoxaban, soya, or to any of the excipients 2.History or evidence of clinically significant renal, hepatic, gastrointestinal, hematological (e.g. anemia), endocrine (e.g. hyper/hypothyroidism, diabetes mellitus), pulmonary or respiratory (e.g. asthma), cardiovascular (e.g. hyper/hypotension), psychiatric, neurologic (e.g. seizures), allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing) or any significant ongoing chronic medical illness. 3.Have body weight is less than or equal to 60 kg at the screening day or during enrollment. 4.Have abnormality of prothrombin time (PT) and activated partial thromboplastin time (aPTT). 5.History or evidence of active clinically significant bleeding e.g. intracranial or intracerebral bleeding, gastrointestinal bleeding. 6.History or evidence of hepatic disease associated with coagulopathy and clinically relevant bleeding risk. 7.Have lesion or condition if considered a significant risk factor for major bleeding including current or recent gastrointestinal ulceration, presence of malignant neoplasms at high risk of bleeding, recent brain or spinal injury, recent brain, spinal or ophthalmic surgery, recent intracranial haemorrhage, known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities. 8.History of problems with swallowing tablet or capsule. 9.History of sensitivity to heparin or heparin-induced thrombocytopenia. 10.Any condition possibly affecting drug absorption e.g. gastrectomy, enterectomy, gastritis or duodenal or gastric ulceration other than appendectomy. 11.History of diarrhea or vomiting within 24 hours prior to check-in in each period. 12.History or evidence of drug addict or investigation with urine sample shows a positive test for drug of abuse (morphine, marijuana or methamphetamine). 13.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 subjects eligibility. 14.12-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 subjects eligibility. 15.Investigation with blood sample shows positive test for HBsAg. 16.Abnormal liver function, is greater than or equal to1.5 times of upper normal limit of reference range for ALT, AST or bilirubin levels at screening laboratory test. 17.Have eGFR (CKD-EPI) is less than or equal to 50 mL/min/1.73 m2 based on serum creatinine results at the screening laboratory test or during enrollment. 18.History or evidence of habitual use of tobacco or nicotine containing products and cannot abstain for at least 48 hours prior to check-in in Period 1 and continued for entire duration of the study. 19.History or evidence of alcoholism or harmful use of alcohol within 2 years prior to screening i.e., alcohol consumption of more than 14 standard drinks per week for men and
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Plasma bisoprolol concentrations 0.00-48.00 hours post-dose Cmax, AUC0-tlast and AUC0-inf will be determined from the plasma concentration data of analytes. | — |
Secondary
| Measure | Time frame |
|---|---|
| Time of the maximum plasma concentration (Tmax) , The elimination half-life (t1/2) and lambdaz will be determined from the plasma concentration data of analytes. 0.00-48.00 hours post-dose Mass spectrometry (LC-MS/MS) | — |
Countries
Thailand
Contacts
Public ContactPorranee Puranajoti
International Bio Service Co., Ltd.
Outcome results
None listed