Bioequivalence Study,
Conditions
Interventions
Generic entecavir 1.0 mg film-
coated tablet,
containing
entecavir 1.0 mg per tablet,Entecavir 1.0 mg film-
Baraclude®,
Reg.
No. 1C 3/52 (N),
containing entecavir 1.0 mg per tablet,
manufactured by ASTRAZENECA PHARMACEUTICAL LP.,
USA and imported by DKSH,
Bangkok,
Active Comparator Drug,Active Comparator Drug
Entecavir plasma concentration (test product), Entecavir plasma concentration (Reference product)
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 18.0 to 30.0 kg/m2. 3 Non-smoker and/or non-consumer of nicotine containing products. Non-smoker means any subject who has never smoked or stopped for at least 90 days whereas non-consumer means any subject who stopped nicotine containing product consumption for at least 90 days. 4 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. 5 Non-pregnant woman (negative pregnancy test) and not currently breast feeding. 6 For female subjects, one of the following must apply: Females of childbearing potential will have to take appropriate measures to prevent pregnancy during the study, such as total abstinence or the use of highly effective contraceptive regimens. Highly effective methods of birth control are defined as those, alone or in combination that result in a low failure rate (i.e. less than 1% per year). Below is a list of acceptable contraceptive regimens throughout the study until duration equal to 1 washout period post last dose: ï€ combined (estrogen and progesterone containing) hormonal contraceptives associated with inhibition of ovulation (oral, intravaginal or transdermal) used for at least 3 consecutive months prior to Period 1 dosing ï€ progestogen-only hormonal contraceptives associated with inhibition of ovulation (oral, injectable or implantable) used for at least 3 consecutive months prior to Period 1 dosing ï€ intrauterine device (IUD) and intrauterine hormone-releasing system (IUS) used for at least 3 consecutive months prior to Period 1 dosing ï€ bilateral tubal occlusion ï€ condom with intravaginally applied spermicides used for at least 14 days prior to Period 1 dosing Females who do not use an acceptable contraceptive regimen or confirm total abstinence will be allowed to participate in this study only if they are not considered to be of childbearing potential: females ï‚· who have had a documented hysterectomy, bilateral oophorectomy, bilateral salpingectomy or tubal ligation, ï‚· or who are clinically diagnosed infertile, ï‚· or who are in a menopausal state (minimum of a year without menses (FSH level >35 IU/mL + no menses since at least 1 year; subjects statement is sufficient). Note: Variations in the FSH levels will be acceptable at the medical discretion of the Principal Investigator or delegated Clinical Investigator after clinical corelation. 7 For male subjects, one of the following must apply in order to avoid impregnating a female partner, from the first study dose until duration equal to 1 washout period post last dose: ï‚· Abstinence ï‚· Use of barrier method with spermicide 8 Subjects have understood and voluntarily given written informed consents (signed and dated) by the subject prior to participating in this study
Exclusion criteria
Exclusion criteria: 1 History of allergic reaction or hypersensitivity to entecavir or any components of the product 2 History or evidence of clinically significant renal, hepatic, gastrointestinal, hematological (e.g. anemia), endocrine (e.g. thyroid), pulmonary or respiratory (e.g. asthma), cardiovascular, psychiatric, 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 History or evidence of galactose intolerance, the Lapp lactase deficiency or glucosegalactose malabsorption 4 History of problems with swallowing tablet or capsule 5 Reports difficulty fasting or consuming standardized meals 6 History of sensitivity to heparin or heparin-induced thrombocytopenia 7 Any condition possibly affecting drug absorption e.g. gastrectomy, enterectomy, gastritis or duodenal or gastric ulceration other than appendectomy 8 History of preceding diarrhea within 24 hours prior to admission in each period 9 Presence of significant infection within 1 week prior to screening or check-in 10 History or evidence of drug addict or investigation with urine sample shows a positive test for drug of abuse (morphine, marijuana, methamphetamine, benzodiazepine or cocaine) 11 Have had a tattoo or body piercing within 90 days prior to the admission in Period 1 or during enrollment 12 Reports a clinically significant illness during the 30 days prior to admission in Period 1 or during enrollment{as determined by the investigator(s)} 13 Pulse rate below 60 beats/minute or above 100 beats/minute 14 Systolic blood pressure less than 90 mmHg or more than 139 mmHg. Diastolic blood pressure less than 60 mmHg or more than 89 mmHg. Minor deviations (2-4 mmHg) at check-in may be acceptable at the discretion of the physician/investigator. 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 should be repeated two more times and the average of the three QTc or QRS values should be used to determine the subject’s eligibility. 16 Investigation with blood sample shows positive test for HBsAg, Anti-HCV or AntiHIV 17 Abnormal liver function, ≥ 1.5 times of upper normal limit of reference range for ALT, AST or bilirubin levels at screening laboratory test 18 History or evidence of alcoholism, regular alcohol consumption or alcohol-containing products and cannot abstain for at least 48 hours prior to admission and continued until last pharmacokinetic blood sample collection in each study period 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. 19 History or evidence of habitual consume of tea, coffee, xanthine or caffeine containing products and cannot abstain for at least 48 hours prior to admission and continued until last pharm
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Entecavir plasma concentration 0-72 hr. Cmax and Truncated AUC0-72 | — |
Secondary
| Measure | Time frame |
|---|---|
| Entecavir plasma concentration 0-72 hrs. Tmax , t1/2 and λz | — |
Countries
Thailand
Contacts
Public ContactUthai Suvanakoot
International Bio Service Co., Ltd
Outcome results
None listed