to compare and evaluate the oral bioavailability of edoxaban 60 mg film coated tablet with that of lixiana® 60 mg filmtabletten (film coated tablet) (edoxaban) in healthy, adult, human subjects under fasting conditions

Conditions: Prevention of Stroke or Systemic Embolism; Deep Vein Thrombosis (DVT); Pulmonary Embolism (PE)

Summary: * to compare and evaluate the oral bioavailability of edoxaban 60 mg film coated tablet with that of lixiana® 60 mg filmtabletten (film coated tablet (edoxaban) in healthy, adult, human subjects under fasting conditions. * to monitor the safety and tolerability of the subjects.


Eligibility criteria:
inclusion criteria: * age: 18 to 55 years old, both inclusive. * gender: male and/or non-pregnant, non-lactating female. a. female of child-bearing potential had a negative serum beta human chorionic gonadotropin (β hcg) pregnancy test performed within 28 days prior to first dosing day. they used an acceptable form of contraception. for female of child-bearing potential, acceptable forms of contraception included the following: i. non hormonal intrauterine device in place for at least 3 months prior to the start of the study and remaining in place during the study period, or ii. barrier methods containing or used in conjunction with a spermicidal agent, or iii. surgical sterilization or iv. practicing sexual abstinence throughout the course of the study. b. female was not considered of child-bearing potential if one of the following was reported and documented on the medical history: i. postmenopausal with spontaneous amenorrhea for at least one year, or ii. spontaneous amenorrhea for more than 6 months and less than one year with serum follicular stimulating hormone (fsh) level \> 40 miu/ml, or iii. bilateral oophorectomy with or without a hysterectomy and an absence of bleeding for at least 6 months, or iv. total hysterectomy and an absence of bleeding for at least 3 months. * bmi: 18.5 to 30.0 kg/m2, both inclusive; bmi value was rounded off to one significant digit after decimal point (e.g. 30.04 rounds down to 30.0, while 18.45 rounds up to 18.5). * volunteers had a body weight of more than 60 kg * non-smokers and non-tobacco users (i.e. had no past history of smoking and tobacco consuming for at least one year prior to study). * able to communicate effectively with study personnel. * willing to provide written informed consent to participate in the study. * all volunteers were judged by the principal or sub-investigator or physician as normal and healthy during a pre-study safety assessment performed within 28 days of the first dose of study medication which will include: 1. a physical examination (clinical examination) with no clinically significant finding. exclusion criteria * history of allergic responses to edoxaban or other related drugs, or any of its formulation ingredients. * had significant diseases or clinically significant abnormal findings during screening \[medical history, physical examination (clinical examination), laboratory evaluations, ecg recording, gynecological history and examination (including pelvic examination and routine breast examination) (for female volunteers)\]. * any disease or condition like diabetes, psychosis or others, which might compromise the haemopoietic, gastrointestinal, renal, hepatic, cardiovascular, respiratory, central nervous system or any other body system. * history or presence of bronchial asthma. * used any hormone replacement therapy within 3 months prior to the first dose of study medication. * used any depot injection or implant of any drug within 3 months prior to the first dose of study medication. * used cyp enzyme inhibitors or inducers within 30 days prior to the first dose of study medication (see https://drug-interactions.medicine.iu.edu/maintable.aspx). * history or evidence of drug dependence or of alcoholism or of moderate alcohol use. * history of difficulty with donating blood or difficulty in accessibility of veins. * a positive hepatitis screen (includes subtypes b \& c). * a positive test result for hiv antibody. * volunteers who had received a known investigational drug within seven elimination half-life of the administered drug prior to the first dose of study medication. * volunteers who had donated blood or loss of blood 50 ml to 100 ml within 30 days or 101 ml to 200 ml within 60 days or \>200 ml within 90 days (excluding volume drawn at screening for this study) prior to first dose of study medication, whichever was greater. * history of difficulty in swallowing or of any gastrointestinal disease, which could affect drug absorption. * intolerance to venipuncture * any food allergy, intolerance, restriction or special diet that, in the opinion of the principal investigator or sub-investigator, could contraindicate the volunteer's participation in this study. * institutionalized volunteers. * used any prescribed medications \[including aspirin and other antiplatelet agents, antithrombotic agents, fibrinolytic therapy, nonsteroidal anti-inflammatory drugs (nsaids), selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors\] within 14 days prior to the first dose of study medication. * used any otc products, vitamin and herbal products, etc., within 7 days prior to the first dose of study medication. * used grapefruit and grapefruit containing products within 7 days prior to the first dose of study medication. * ingestion of any caffeine or xanthine products (i.e. coffee, tea, chocolate, and caffeine-containing sodas, colas, etc.), recreational drugs, alcohol or other alcohol containing products within 48 hours prior to the first dose of study medication. * ingestion of any unusual diet, for whatever reason (e.g.: low sodium) for three weeks prior to the first dose of study medication. * volunteer had a platelet count below the lower limit of the normal range during screening. * volunteer had an inr and prothrombin time and/or activated partial thromboplastin time value higher than 1.1 times of the upper limit of normal ranges during screening. * volunteers had sgpt, sgot and alkaline phosphatase values 1.1 times higher than the upper limit of normal range during screening. * volunteers had serum bilirubin value higher than the upper limit of normal range during screening. * history of bleeding disorders or any significant family history of bleeding disorders. * history of prosthetic heart valve or history of pulmonary embolism. * history of traumatic or repeated epidural or spinal puncture or plan for spinal surgery/spinal procedure or volunteer having any spinal deformity or neurological impairment. * creatinine clearance below 60 ml/min during screening. * history or presence of active pathological bleeding.