Pharmacokinetics of Two Formulations of Entecavir

A Randomized, Parallel, Single-Dose Study to Evaluate the Pharmacokinetics of a Test Formulation of Entigin Film Coated Tablet 0.5mg (Entecavir 0.5 mg), Compared to an Equivalent Dose of a Reference Drug Product (Baraclude 0.5mg Tablets) in Healthy Adult Subjects

A Randomized, Parallel, Single-Dose Study to Evaluate the Pharmacokinetics of a Test Formulation of Entigin Film Coated Tablet 0.5mg (Entecavir 0.5 mg), Compared to an Equivalent Dose of a Reference Drug Product (Baraclude 0.5mg Tablets) in Healthy

Study Overview

• Status: Completed
• Conditions: Hepatitis B
• Intervention / Treatment: Drug: Entigin Film Coated Tablet 0.5mg; Drug: (Baraclude 0.5mg Tablets

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy adult, aged between 20 to 45 years old.

2. Physically and mentally healthy subjects as confirmed by an interview, medical history, clinical examination, laboratory tests, chest x-ray and electrocardiogram.

   • no particular clinical significance in clinical examination and laboratory tests within two months (60 days) prior to administration of study medication.
   • normal or considered not clinically significant by the investigator chest X-ray and Electrocardiogram (ECG) results within six months(180 days)prior to administration of study medication.
3. Body weight must be above 50 kg for male and 45 kg for female.
4. The normal range of the body mass index should be between 18 and 30; body mass index equals [weight (kg)]/[height (m)]2.
5. Laboratory determinations results are within normal range or considered not clinically significant by the investigator, including: Serum Glutamic Oxaloacetic Transaminase (SGOT, same as AST), Serum Glutamic Pyruvic Transaminase (SGPT, same as ALT), albumin, glucose, creatinine, uric acid, cholesterol, Triglycerides (TG), Gamma-Glutamyl-Transpeptidase (γ-GT), alkaline phosphatase, total bilirubin, Blood Urea Nitrogen (BUN), Hepatitis B surface antigen (HBsAg), Anti-Hepatitis C virus (HCV) and Anti-Human Immunodeficiency Virus (HIV) test.
6. Hematology test results are within normal range or considered not clinically significant by the investigator, including: hemoglobin, hematocrit, White Blood Cell (WBC) count, Red Blood Cell (RBC) count, platelet count and WBC count with differential.
7. Urinalysis results are within normal range or considered not clinically significant by the investigator, including: glucose, protein, RBC, WBC, epithelial cells, casts and bacteria.

8. Female subject who is:

   • using adequate contraception since last menstruation and no plan for conception during the study.
   • non-lactating.
   • has negative pregnancy test (urine) prior to the study.
9. Informed consent form signed.

Exclusion Criteria:

1. A history of drug or alcohol abuse during the past 24 weeks.
2. Sensitivity to analogous drug.
3. A clinically significant illness (such as lactic acidosis or severe hepatomegaly with steatosis) within the past 4 weeks.
4. Evidence of any clinical significant renal, cardiovascular, hepatic, hematopoietic, neurological, pulmonary or gastrointestinal pathology within the past 4 weeks.
5. Planned vaccination during the time course of the study.
6. Participation of any clinical investigation during the last 60 days.
7. Regular use of any medication during the last 4 weeks.
8. Single use of any medication during the last 2 weeks.
9. Blood donation of more than 250 mL within the past 12 weeks.
10. Employees and their families of sponsor and/or Contract Research Organization (CRO) company.
11. Individuals are judged by the investigator or co-investigator to be undesirable as subjects.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Entigin Film Coated Tablet 0.5mg; Entigin Film Coated Tablet 0.5mg Dosing Regimen: Single dosing of two tablets	Drug: Entigin Film Coated Tablet 0.5mg
ACTIVE_COMPARATOR: Baraclude 0.5mg Tablets; Baraclude 0.5mg Tablets Dosing Regimen: Single dosing of two tablets	Drug: (Baraclude 0.5mg Tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the plasma concentration(AUC)	Plasma sample: 0, 0.167, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 84, 132 and 168 hr Urine sample: -2~0, 0~6, 6~12, 12~24, 24~36, 36~48 hr
Time to reach Cmax(Tmax)	Plasma sample: 0, 0.167, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 84, 132 and 168 hr Urine sample: -2~0, 0~6, 6~12, 12~24, 24~36, 36~48 hr
Peak Drug Concentration(Cmax)	Plasma sample: 0, 0.167, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 84, 132 and 168 hr Urine sample: -2~0, 0~6, 6~12, 12~24, 24~36, 36~48 hr
Elimination half-life(T1/2)	Plasma sample: 0, 0.167, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 84, 132 and 168 hr Urine sample: -2~0, 0~6, 6~12, 12~24, 24~36, 36~48 hr
Area under the (first) moment plasma concentration-time curve(AUMC)	Plasma sample: 0, 0.167, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 84, 132 and 168 hr Urine sample: -2~0, 0~6, 6~12, 12~24, 24~36, 36~48 hr
Mean Residence Time(MRT)	Plasma sample: 0, 0.167, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 84, 132 and 168 hr Urine sample: -2~0, 0~6, 6~12, 12~24, 24~36, 36~48 hr

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of Treatment-Emergent Adverse Events	The safety was monitored throughout the study. Up to 10 weeks

Collaborators and Investigators

• Sponsor: Yung Shin Pharm. Ind. Co., Ltd.
• Collaborators: Taichung Veterans General Hospital

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (ACTUAL): February 1, 2016
• Study Completion (ACTUAL): February 1, 2016

Study Registration Dates

• First Submitted: June 16, 2016
• First Submitted That Met QC Criteria: July 27, 2016
• First Posted (ESTIMATE): August 1, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): August 1, 2016
• Last Update Submitted That Met QC Criteria: July 27, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Pharmacokinetic
• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis; Hepatitis B; Anti-Infective Agents; Antiviral Agents; Entecavir
• Other Study ID Numbers: YSP RHH3001-01