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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Hepatitis B, Chronic

Intervention / Treatment
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* Drug: Freethiadine tablets(part I)
* Drug: Freethiadine tablets (part II)
* Drug: Freethiadine placebo tablets
* Drug: entecavir tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Health volunteer: Sign the informed consent form before the trial and fully understand the contents of the trial, the process and possible adverse reactions. subjects and must be 18 to 45 years of age inclusive. Body weight ≥ 45 kg and body mass index（BMI）between 18 and 28 kg / m^2, inclusive. Physical examination and vital signs without clinically significant abnormalities. Patients with chronic hepatitis B: Sign the informed consent form before the trial and fully understand the contents of the trial, the process and possible adverse reactions. subjects and must be 18 to 65 years of age inclusive. Body mass index（BMI）between 18 and 32 kg / m^2, inclusive. No cirrhosis. Exclusion Criteria: Health volunteer: Use of >5 cigarettes per day during the past 3 months. 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). Donation or loss of blood over 450 mL within 3 months prior to screening. Patients with chronic hepatitis B: AFP>50 ng/mL. INR>1.5. Positive for Viral hepatitis C, HIV and syphilis.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Freethiadine tablets<br>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)<br>* 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)<br>|
| Placebo Comparator: Freethiadine placebo tablets<br>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<br>* 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)<br>|
| Experimental: Freethiadine tablet<br>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)<br>* once or twice daily for consecutive 28 days<br>|
| Active Comparator: entecavir tablets<br>part 2(Patients with chronic hepatitis B): 0.5 mg | Drug: entecavir tablets<br>* once daily for consecutive 28 days<br>|

What is the study measuring?
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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 |