A Single Dose, Randomized, Open-label, Balanced, Two-way Crossover Bioequivalence Study of Generic Apixaban 5 mg Film-coated Tablets and Reference Product (ELIQUIS Apixaban 5 mg Film-coated Tablets) in Healthy Thai Volunteers under Fasting Conditions
- Conditions
- Apixaban 5 mg Film-coated Tablets in Healthy Thai VolunteersBioequivalence Study Healthy Thai Volunteers
- Registration Number
- TCTR20210824006
- Lead Sponsor
- International Bio Service Co., Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending (Not yet recruiting)
- Sex
- All
- Target Recruitment
- 28
1.Healthy Thai male or female subjects between the ages of 18 to 55 years.
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-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 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 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:
Postmenopausal for at least 1 year or Surgically sterile (bilateral tubal ligation, bilateral oophorectomy oror 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 7 days after the end of study in Period 2.
7.Have voluntarily given written informed consents (signed and dated) by the subject prior to participating in this study.
1.History of allergic reaction or hypersensitivity to apixaban 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 (e.g. depression), neurologic (e.g. convulsion), 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 about administration of first dose or second dose of COVID-19 vaccine within 30 days prior to check-in in each Period.
5.History or evidence of clinically significant active bleeding
6.Have abnormality of prothrombin time (PT) and activated partial thromboplastin time (aPTT)
7.History or evidence of hepatic disease associated with coagulopathy and clinically relevant bleeding risk
8.Has 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.
9.History or evidence of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
10.History of problems with swallowing tablet or capsule
11History of sensitivity to heparin or heparin-induced thrombocytopenia
12.12.Any condition possibly affecting drug absorption e.g. gastrectomy, enterectomy, gastritis or duodenal or gastric ulceration other than appendectomy
13.History of vomiting or diarrhea within 24 hours prior to check-in in each period
14.History or evidence of drug addict or investigation with urine sample shows a positive test for drug of abuse (morphine, marijuana or methamphetamine)
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 eligibility.
16.Investigation with blood sample shows positive test for HBsAg
17.Abnormal liver function, more than 1.5 times of upper normal limit of reference range for ALT, AST or bilirubin levels at screening laboratory test
18.Has renal creatinine clearance (Clcr) < 50 mL/min based on serum creatinine results, using glomerular filtration rate (GFR; Cockcroft-Gault formula), at the screening laboratory test
19.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
20.History or evidence of alcoholism or harmful use of alcohol (less than 2 years) i.e., alcohol consumption of more than 14 standard drinks per week for men and 7 standard drinks per week for women (A standard drink is defined as 360 mL of beer or 150 mL of wine or 45 mL of 40% distilled spirits, such as rum, whisky, brandy etc.)
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Plasma Apixaban concentrations 23 points 0-48 hours post dose Cmax, AUC0-tlast and AUC0-infinity
- Secondary Outcome Measures
Name Time Method Plasma Apixaban concentrations 23 points 0-48 hours post dose Tmax, t1/2, AUC0-tlast/AUC infinity , AUC%extrapolate,