| Eligibility |
Inclusion Criteria:
- 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.
- Body mass index between 18.5 to 30.0 kg/m2
- 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
- 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.
- Non-pregnant woman (negative pregnancy test) and not currently breast feeding.
- 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
- 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.
- Able to understand and voluntarily given written informed consent (signed and dated)
by the subject prior to participating in this study.
- Adequate venous access in both arms for the collection of a number of samples during
the study.
Exclusion Criteria:
- History of hypersensitivity to dabigatran or dabigatran etexilate or to any of the
excipients of product
- 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. Have high risk for
coronavirus infection based on risk assessment questionnaire or diagnosed as confirmed
case of COVID-19.
- History about administration of COVID-19 vaccine within 30 days prior to check-in in
each Period.
- Have eGFR (CKD-EPI) < 50 mL/min/1.73 m2 based on serum creatinine results, at the
screening laboratory test or during enrollment.
- History or evidence of haemorrhagic manifestations, patients with a bleeding diathesis
or patients with spontaneous or pharmacological impairment of haemostasis.
- History or evidence of organ lesions at risk of clinically significant bleeding,
including haemorrhagic stroke within the last 6 months.
- History or evidence of surgery for prosthetic heart valve replacement.
- History or evidence of surgery for knee or hip replacement.
- History or evidence of venous thromboembolic events, deep vein thrombosis or pulmonary
embolism.
- History or evidence of stroke.
- History or evidence of atrial fibrillation.
- History of sensitivity to heparin or heparin-induced thrombocytopenia.
- Any condition possibly affecting drug absorption e.g. gastrectomy, enterectomy,
gastritis or duodenal or gastric ulceration other than appendectomy.
- History of diarrhea or vomiting within 24 hours prior to check-in in each period.
- History of problems with swallowing tablet or capsule.
- History or evidence of drug addict or investigation with urine sample shows a positive
test for drug of abuse (morphine, marijuana or methamphetamine).
- 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.
- Investigation with blood sample shows positive test for HBsAg.
- Abnormal liver function, =1.5 times of upper normal limit of reference range for ALT,
AST or bilirubin levels at screening laboratory test. 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.).
- 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% BAC and the physician carefully considers that the value came from other
reasons, not from the alcohol drinking behavior of subjects, the test will be repeated
two times separately, not more than 10 minutes. The result of the last time should be
used for subject's eligibility which must be 0 mg%BAC.
- History or evidence of habitual consume of any caffeine- or xanthine-containing
products e.g. tea, coffee, chocolate, colas etc. and cannot abstain for at least 72
hours prior to check-in and continued for entire duration of the study.
- Consume or drink juice of grapefruit or orange or pomelo or its supplement/ containing
products and cannot abstain for at least 7 days prior to check-in and continued for
entire duration of the study.
- Use of prescription or nonprescription drugs (e.g. paracetamol, amiodarone, verapamil,
quinidine, ketoconazole, dronedarone, ticagrelor, clarithromycin, other
anticoagulants, NSAIDs, selective serotonin reuptake inhibitors, selective serotonin
norepinephrine reuptake inhibitors, fibrinolytic agents and etc.), herbal medications
or supplements (e.g. St. John's wort), vitamins or mineral (e.g. iron) or dietary
supplements within 14 days prior to check-in in Period 1 and continued for entire
duration of the study
- Participated in other clinical trials within 90 days prior to check-in in Period 1
(except for the subjects who drop out or withdrawn from the previous study prior to
Period 1 dosing) or still participates in the clinical trial or participates in other
clinical trials during enrollment in this study
- Blood donation or blood loss = 1 unit (1 unit is equal to 350-450 mL of blood) within
90 days prior to check-in in Period 1 or during enrollment.
- Subjects with poor venous access or intolerant to venipuncture.
- Unwilling or unable to comply with schedule visit, treatment plan and other study
procedures until end of study.
- Inability to communicate well (i.e. language problem, poor mental development,
psychiatric illness or poor cerebral function) that may impair the ability to provide
written informed consent or cooperate with clinical team.
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