Evaluation Freethiadine Tolerance in Healthy Subjects and Patients With Chronic Hepatitis B, Pharmacokinetics Characteristics and Antiviral Activity of Ⅰ Phase of Study

A Phase 1, Randomized, Double-blind, Placebo-controlled, Single- and Multiple-dose Study in Healthy Subjects and Chronic Hepatitis B Subjects to Evaluate the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of Freethiadine

The Safety, Tolerability, Pharmacokinetics and antiviral activity Study of Anti hepatitis B virus treatment drug Freethiadine in Healthy subjects and in patients with chronic hepatitis B

Study Overview

• Status: Completed
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Drug: Freethiadine tablets(part I); Drug: Freethiadine placebo tablets; Drug: Freethiadine tablets (part II); Drug: entecavir tablets

• Study Type: Interventional
• Enrollment (Actual): 128
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Southern Hospital of Southern Medical University
  • Jilin
    • Changchun, Jilin, China, 130000
      • The First Hospital of Jilin University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Health volunteer:

1. Sign the informed consent form before the trial and fully understand the contents of the trial, the process and possible adverse reactions.
2. subjects and must be 18 to 45 years of age inclusive.
3. Body weight ≥ 45 kg and body mass index（BMI）between 18 and 28 kg / m^2, inclusive.
4. Physical examination and vital signs without clinically significant abnormalities.

Patients with chronic hepatitis B:

1. Sign the informed consent form before the trial and fully understand the contents of the trial, the process and possible adverse reactions.
2. subjects and must be 18 to 65 years of age inclusive.
3. Body mass index（BMI）between 18 and 32 kg / m^2, inclusive.
4. No cirrhosis.

Exclusion Criteria:

Health volunteer:

1. Use of >5 cigarettes per day during the past 3 months.
2. History of alcohol abuse (14 units of alcohol per week: 1 unit = 285 mL of beer, or 25 mL of spirits or 100 mL of wine).
3. Donation or loss of blood over 450 mL within 3 months prior to screening.

Patients with chronic hepatitis B:

1. AFP>50 ng/mL.
2. INR>1.5.
3. Positive for Viral hepatitis C, HIV and syphilis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: entecavir tablets; part 2(Patients with chronic hepatitis B): 0.5 mg	Drug: entecavir tablets; once daily for consecutive 28 days
Experimental: Freethiadine tablets; part 1(Health volunteer): single-Dose Study: There will be a total of 5 dose cohorts: 5 mg、10 mg、200 mg(food effect)、400 mg、600 mg; multiple-dose study: 100 mg、200 mg、300 mg、150 mg	Drug: Freethiadine tablets(part I); Subjects will receive either a single dose of Freethiadine on Day 1 only (SAD HV), twice daily dosing of Freethiadine starting on Day 1 through Day 10 (MAD HV)
Placebo Comparator: Freethiadine placebo tablets; part 1(Health volunteer): single-Dose Study: There will be a total of 5 dose cohorts: 5 mg、10 mg、200 mg(food effect)、400 mg、600 mg; multiple-dose study: 100 mg、200 mg、300 mg、150 mg	Drug: Freethiadine placebo tablets; Subjects will receive either a single dose of Freethiadine on Day 1 only (SAD HV), twice daily dosing of Freethiadine starting on Day 1 through Day 10 (MAD HV)
Experimental: Freethiadine tablet; part 2(Patients with chronic hepatitis B): There will be a total of 4 dose cohorts:100 mg、200 mg(BID or QD)、300 mg	Drug: Freethiadine tablets (part II); once or twice daily for consecutive 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Incidence of adverse events	From Days 1-35
AUC	Maximum plasma concentration of study drugs	Day 1-12
HBV DNA	Change from baseline in HBV DNA	Day 1-35

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HBsAg	Change from baseline in HBsAg	Day 1-35

Collaborators and Investigators

• Sponsor: Sunshine Lake Pharma Co., Ltd.
• Investigators: Principal Investigator: junqi Niu, Doctor, The First Hospital of Jilin University; Principal Investigator: JinLin Hou, Doctor, Southern Hospital of Southern Medical University

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2021
• Primary Completion (Actual): January 17, 2023
• Study Completion (Actual): January 17, 2023

Study Registration Dates

• First Submitted: May 20, 2022
• First Submitted That Met QC Criteria: May 20, 2022
• First Posted (Actual): May 25, 2022

Study Record Updates

• Last Update Posted (Actual): April 12, 2023
• Last Update Submitted That Met QC Criteria: April 11, 2023
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Anti-Infective Agents; Antiviral Agents; Entecavir
• Other Study ID Numbers: HEC160208-HBV-101

Drug and device information, study documents

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