The Tolerability, Pharmacokinetics and Pharmacodynamics Study of HEC74647 in HCV-infected Subjects

Study Overview
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Brief Summary
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The goal of this study is to assess the tolerability, pharmacokinetics and antiviral activity of HEC74647 in HCV treatment naïve subjects with genotypes 1-6.

Detailed Description
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All subjects will be receive QD doses of HEC74647 or the matching placebo for 3 days to assess the the tolerability, pharmacokinetics and antiviral activity at specified time-points during the study.All subjects also will be monitored for up to 8 days post-dose to determine the persistence of viral mutations.

Official Title
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A Single-center, Randomized, Double-blind, Parallel, Placebo-controlled, Multiple Consecutive Dose Study to Assess the Tolerability, Pharmacokinetics and Pharmacodynamics of HEC74647 in Subjects With Chronic Hepatitis C Virus Infection

Conditions
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Chronic Hepatitis C

Intervention / Treatment
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* Drug: HEC74647PA capsule
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to comprehend and sign the ICF voluntarily prior to initiate the study; Able to complete the study according to the protocol; Agree to use protocol defined precautions against pregnancy Body weight of male and female subject should be ≥50 kg and ≥45 kg respectively; Body Mass Index (BMI) is between 18 and 30 kg/m2, inclusive; HCV treatment-naïve adult subjects with GT1-6 HCV infection HCV RNA level ≥ 5 log10 IU/mL at screening FibroScan score within 6 months≤12.5 kPa or Liver biopsy results within 12 months proved Non-cirrhosis Exclusion Criteria: Smokers, who smoke more than 5 cigarettes/day within 3 months before the study; Drink frequently, namely alcohol consumption are 14 units per week (1 unit = 285 mL of beer, or 25 mL of strong wine, or 100 mL of grape wine); Donated blood or massive blood loss within 3 months before screening (>450 mL）; Have any disease that increases the risk of bleeding, such as acute gastritis or stomach and duodenal ulcers; Have taken any prescription drug, over-the-counter drug, vitamin product or herbal medicine within 14 days prior to screening; Have taken any drug that inhibit gastric acid secretion, such as H2 receptor antagonist famotidine and proton pump inhibitor omeprazole; Have participated in any clinical trial or taken any study drug within 3 months before dosing; Positive test result of HBV,HIV or syphilis; Solid organ transplanters

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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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>up to HEC74647PA capsule 50 mg once daily for 3 days | Drug: HEC74647PA capsule<br>* Capsule administered orally once daily<br>|
| Experimental: Cohort 2<br>up to HEC74647PA capsule 100 mg once daily for 3 days | Drug: HEC74647PA capsule<br>* Capsule administered orally once daily<br>|
| Experimental: Cohort 3<br>up to HEC74647PA capsule 200 mg once daily for 3 days | Drug: HEC74647PA capsule<br>* Capsule administered orally once daily<br>|
| Placebo Comparator: Cohort 4<br>up to placebo once daily for 3 days | Drug: placebo<br>* HEC74647PA capsule matching placebo administered orally once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events,laboratory abnormalities and other abnormalities | Number of participants with Adverse Events, laboratory abnormalities and other abnormalities following dose administration of HEC74647 | 8 days | 
| Antiviral Activity | Change from baseline in HCV RNA following dose administration of HEC74647 | 8 days | 
| Sequence changes in the NS5A coding region | Sequence changes in the NS5A coding region of HCV following multiple dose administration of HEC74647 and for up to 8 days thereafter | 8 days | 
| Cmax | Maximum observed plasma concentration of HEC74647 | 8 days | 
| Tmax | Time of the maximum observed plasma concentration | 8 days | 
| AUC | Area under the plasma concentration-time curve (AUC) | 8 days | 
| t1/2 | Terminal elimination half-life | 8 days |