Bioequivalence Study of Entecavir Tablets and Baraclude® Under Fasting Condition in Chinese Healthy Volunteers

A Single-Center, Open-Label, Randomized, Single-Dose, Two-Period, Two-Sequence, Crossover Study to Assess the Bioequivalence of Entecavir Tablets 1.0 mg With Baraclude® 1.0 mg in Healthy Adult Subjects Under Fasting Conditions

A single-center, open-Label, randomized, single-dose, two-period, two-sequence, crossover study to assess the bioequivalence of test formulation entecavir tablets 1.0 mg with reference formulation entecavir tablets (Baraclude®) 1.0 mg in healthy adult subjects under fasting conditions.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis b
• Intervention / Treatment: Drug: Baraclude® tablets,1.0 mg; Drug: Entecavir tablets,1.0 mg

Detailed Description

This is a single-center, open-label, randomized, single-dose, two-period, two-sequence, crossover study to assess the bioequivalence of test formulation Entecavir Tablets 1.0 mg with reference formulation Entecavir Tablets (Baraclude®) 1.0 mg in healthy adult subjects under fasting conditions. Each subject will be randomized to one of two treatment sequences (TR, RT) according to a randomization schedule prepared prior to the start of the study. There will be a 21-day washout between each single dose administration. Subjects in each group will be dosed on the same day for Day 1 of Period 1, and all subjects in each group will be crossed over to the alternate formulation and will be dosed on the same day for Day 22 of Period 2.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shandong
    • Ji'nan, Shandong, China, 250013
      • Ji'nan Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Able to give signed Informed Consent Form before study, and fully understand the study content, process and possible adverse reactions;
2. Able to complete the study in compliance with the protocol;
3. Subjects (including male subjects) agree to adopt effective contraceptive measurements and not plan pregnancy from 14 days before screening to 6 months after study completion;
4. Healthy male and female subjects between 18 and 50 years of age, inclusive;
5. At least 50 kg for male subjects, 45 kg for female subjects, with a Body Mass Index (BMI= Weight/Height2 kg/m2) between 18.0-28.0, inclusive.

Exclusion Criteria:

1. More than 5 cigarettes per day on average within 3 months before the study;
2. A history of allergies (such as asthma, measles, eczema, etc.), or allergic constitution (allergic to two or more drugs or food such as milk and pollen), or a history of allergy to Entecavir and its inactive ingredient;
3. A history of alcohol abuse (at least 14 units of alcohol per week: 1 units = 285 mL beer, 25 mL spirit or 100 mL wines);
4. Donation or loss of a significant volume of blood (> 400 mL) within 3 months prior to receiving study medication;
5. History of difficulties in swallowing, or any gastrointestinal disease which could affect the drug absorption;
6. History of Lactic acidosis and / or severe hepatomegaly with steatosis;
7. Use of any prescription drugs within 14 days prior to receiving study medication;
8. Use of any over-the-counter (OTC) drugs, dietary or herbal supplements within 7 days prior to receiving study medication;
9. Consumption of any special diet (including grapefruit and products containing grapefruit) or subjects have exercised strenuously or have any other factors affecting drug absorption, distribution, metabolism and excretion within 7 days prior to receiving study medication.
10. Participation in other drug clinical study within 3 months prior to receiving study medication;
11. Any clinically significant abnormalities/findings, as judged by the Investigator, including laboratory tests, vital signs, electrocardiogram, and physical examination; Or have a serious history of heart, liver, kidney, digestive tract, nervous system, respiratory system, mental disorders and metabolic abnormalities, which the Investigator considers inappropriate for participants;
12. A positive test result for hepatitis B surface antigen (HBsAg), hepatitis C antibody, HIV antibody or syphilis;
13. Consumption of chocolate or any food or beverages containing caffeine or (rich containing) xanthine within 48 h prior to receiving study medication;
14. Consumption of any product containing alcohol within 24 h prior to receiving study medication or a positive result of alcohol test;
15. A positive test result for drug screening or a history of drug abuse within 5 years or use of any controlled substances within 3 months before the study;
16. A positive pregnancy test or subject is lactating during screening or study period if the subject is female;
17. Any condition which in the opinion of Investigator is not suitable for subjects to participate in the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Baraclude® tablets，1.0 mg	Drug: Baraclude® tablets,1.0 mg; oral,once,under fasting condition
EXPERIMENTAL: Entecavir tablets，1.0 mg	Drug: Entecavir tablets,1.0 mg; oral,once,under fasting condition

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Peak Plasma Concentration (Cmax) of Entecavir.	Cmax will be obtained on Day 1 within 60 minutes pre-dose and 10 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.25 hours, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 48 hours and 72 hours post-dose.
AUC0-t、AUC0-∞	Area under the plasma concentration versus time curve (AUC) of Entecavir.	AUC will be obtained on Day 1 within 60 minutes pre-dose and 10 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.25 hours, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours,24 hours, 48 hours and 72 hours post-dose.

Collaborators and Investigators

• Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 4, 2018
• Primary Completion (ACTUAL): December 28, 2018
• Study Completion (ACTUAL): December 28, 2018

Study Registration Dates

• First Submitted: January 22, 2019
• First Submitted That Met QC Criteria: February 19, 2019
• First Posted (ACTUAL): February 20, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 20, 2019
• Last Update Submitted That Met QC Criteria: February 19, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• 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, Chronic; Hepatitis; Hepatitis B; Hepatitis B, Chronic; Anti-Infective Agents; Antiviral Agents; Entecavir
• Other Study ID Numbers: CTTQ-2018-001-JN

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No