A Single Dose, Randomized, Open-label, Two-treatment, Four-period, Two-sequence, Replicate Crossover Bioequivalence Study of Generic Dabigatran Etexilate Capsules 150 mg and Reference Product (Pradaxa) in Healthy Thai Volunteers under Fasting Conditions
- Conditions
- Bioequivalence Study Healthy Thai VolunteersDabigatran etexilate 150 mg Capsules in Healthy Thai Volunteers
- Registration Number
- TCTR20230427002
- 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
- 48
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 18.5 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-smoker and non-consumer of nicotine containing products
Non-smoker or non-consumer of nicotine containing products means any subject who has never smoked/consumed 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 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 4. 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
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 4.
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
1.History of hypersensitivity to dabigatran or dabigatran etexilate or to any of the excipients of product
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 (e.g. hyper-/hypotension), 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 about administration of COVID-19 vaccine within 30 days prior to check-in in each Period.
5.Have renal creatinine clearance (CrCl) < 50 mL/min based on serum creatinine results, using glomerular filtration rate (GFR; Cockcroft-Gault formula), at the screening laboratory test
6.History or evidence of haemorrhagic manifestations, patients with a bleeding diathesis or patients with spontaneous or pharmacological impairment of haemostasis
7.History or evidence of organ lesions at risk of clinically significant bleeding, including haemorrhagic stroke within the last 6 months
8.History or evidence of surgery for prosthetic heart valve replacement
9.History or evidence of surgery for knee or hip replacement
10.History or evidence of venous thromboembolic events, deep vein thrombosis or pulmonary embolism.
11.History or evidence of stroke
12.History or evidence of atrial fibrillation
13.History of sensitivity to heparin or heparin-induced thrombocytopenia
14.Any condition possibly affecting drug absorption e.g. gastrectomy, enterectomy, gastritis or duodenal or gastric ulceration other than appendectomy
15.History of diarrhea or vomiting within 24 hours prior to check-in in each period
16.History of problems with swallowing tablet or capsule
17.History or evidence of drug addict or investigation with urine sample shows a positive test for drug of abuse (morphine, marijuana or methamphetamine)
18.12-lead ECG demonstrating QTc more than 450 msec, a QRS interval more than120 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.
19.Investigation with blood sample shows positive test for HBsAg
20.Abnormal liver function, more than or equal 1.5 times of upper normal limit of reference range for ALT, AST or bilirubin levels at screening laboratory test
21.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.)
22.History or evidence of alcohol consumption or alcohol-containing products and cannot abstain for at least 48 hours prior to check-in and continued for entire duration of the study or alcohol breath test shows positive result
In case of alcohol breath test result represents the alcohol concentration range of 1 - 10 mg percent BAC and the physician carefully considers that the value came from other reasons, not from the alcohol drinking b
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method free dabigatran and total dabigatran concentration 0-48 hrs Cmax AUC0-tlast and AUC infinaity
- Secondary Outcome Measures
Name Time Method free dabigatran and total dabigatran concentration 0-48 hrs Tmax ,t1/2 ,AUC0-tlast and AUC infinity, AUC extrapolate