A Single Dose, Randomized, Open-label, Two-way Crossover Bioequivalence Study of Entecavir 1.0 mg Film-coated Tablets and Reference Product (Baraclude®) in Healthy Thai Volunteers under Fasting Conditions
- Conditions
- VolunteersBioequivalence Study,Healthy,Thai,Entecavir,
- Registration Number
- TCTR20190606006
- Lead Sponsor
- International Bio Service Co. Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 26
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
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Entecavir plasma concentration 0-72 hr. Cmax and Truncated AUC0-72
- Secondary Outcome Measures
Name Time Method Entecavir plasma concentration 0-72 hrs. Tmax , t1/2 and λz