The Tolerability, Pharmacokinetics and Pharmacodynamics Study of HEC110114 Tablets in HCV-infected Subjects

Study Overview
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Brief Summary
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A Phase Ib/IIa, Single Center, Randomized, open, Sofosbuvir-controlled, Multiple Ascending Dose Study to Access the Tolerability，Pharmacokinetics and Pharmacodynamics of HEC110114 Tablets in HCV-infected Subjects

Detailed Description
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A total of 24 evaluable patients will be enrolled in this study. The study randomly divided into three dose groups and HEC110114 tablets planned dose levels are 600, 800, and 1200 mg, sofosbuvir tablets planned dose levels are 400 mg .

Official Title
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A Phase Ib/IIa, Single Center, Randomized, Open, Sofosbuvir-controlled, Multiple Ascending Dose Study to Access the Tolerability， Pharmacokinetics and Pharmacodynamics of HEC110114 Tablets in HCV-infected Subjects

Conditions
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Chronic Hepatitis C

Intervention / Treatment
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* Drug: HEC110114 Tablet
* Drug: Sofosbuvir Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sign the informed consent form before the trial and fully understand the contents of the trial, the process and possible adverse reactions; Be able to complete the study according to the trail protocol; Subjects (including partners) have no pregnancy plan within six months after the last dose of study drug and voluntarily take effective contraceptive measures; Male subjects and must be 18 to 65 years of age inclusive; Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive, and a body weight ≥50 kg for males and ≥45 kg for females; No previous treatment with any direct-acting antiviral (DAA) drugs for HCV, such as Simeprevir, Sofosbuvir, Daclatasvir etc; HCV RNA ≥10*5 IU/mL at screening (Roche COBAS Taqman); Chronic genotype 1-6 HCV Infection, multiple genotypes, subtype unidentifiable or others ; Serum ALT ≤5 times ULN. Exclusion Criteria: Allergies constitution ( multiple drug and food allergies); 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; History of any non-HCV liver diseases, including but not limited to hemochromatosis, primary biliary cirrhosis, Wilson's disease, autoimmune hepatitis, drug or alcoholic hepatitis, non-alcoholic steatohepatitis, etc; 12-lead ECG with clinically significant; Pregnant or lactating women; Creatinine clearance < 60 mL/min; Subjects deemed unsuitable by the investigator for any other reason.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 600 mg multiple doses<br>Subjects receiving 600 mg HEC110114 tablet (N=6) or sofosbuvir tablets(N=2) once daily (q.d.) for 3 days | Drug: HEC110114 Tablet<br>* administered orally once daily<br>Drug: Sofosbuvir Tablet<br>* administered orally once daily<br>|
| Experimental: 800 mg multiple doses<br>Subjects receiving 800 mg HEC110114 tablet (N=6) or sofosbuvir tablets(N=2) once daily (q.d.) for 3 days | Drug: HEC110114 Tablet<br>* administered orally once daily<br>Drug: Sofosbuvir Tablet<br>* administered orally once daily<br>|
| Experimental: 1200 mg multiple doses<br>Subjects receiving 1200 mg HEC110114 tablet (N=6) or sofosbuvir tablets(N=2) once daily (q.d.) for 3 days | Drug: Sofosbuvir Tablet<br>* 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 | Incidence of adverse events | From Days 1-10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum Observed Plasma Concentration | At pre-defined intervals from Days 1-7 | 
| Tmax | Time to Maximum Observed Plasma Concentration | At pre-defined intervals from Days 1-7 | 
| T1/2 T1/2 T1/2 T1/2 | Apparent Half-Life | At pre-defined intervals from Days 1-7 | 
| AUClast | Area Under the Plasma Concentration vs Time Curve to Last Measurable Concentration | At pre-defined intervals from Days 1-7 | 
| HCV RNA | HCV RNA declined from baseline | At pre-defined intervals from Days 1-10 |