The Tolerability and Pharmacokinetics Study of HEC74647PA Capsule in Healthy Adult Subjects

Study Overview
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Brief Summary
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The Tolerability and Pharmacokinetics Study of HEC74647PA Capsule in Healthy Adult Subjects

Detailed Description
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A Phase I, Single Center, Randomized, Double-blind, Placebo-controlled, Single & Multiple Ascending Dose Study to Access the Tolerability and Pharmacokinetics of HEC74647PA Capsule in Healthy Adult Subjects.

Official Title
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A Phase I, Single-center, Randomized，Double-blind, Placebo-controlled, Single & Multiple Ascending Dose Study to Assess the Tolerability and Pharmacokinetics of HEC74647PA Capsule in Healthy Adult Subjects

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; Between 18 and 45 years of age, inclusive, male subject should be no fertility needs; Body weight of male and female subject should be ≥50 kg and ≥45 kg respectively; Body Mass Index (BMI) is between 18 and 28 kg/m2, inclusive; Physical examination and vital signs without clinically significant abnormalities. 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 acne, acute gastritis or stomach and duodenal ulcers; Have taken any prescription drug, over-the-counter drug, vitamin product or herbal medicine within 1 month prior to screening; Have participated in any clinical trial or taken any study drug within 3 months before dosing; Viral hepatitis（including CHB and CHC）and positive test result of anti-HIV Ab or syphilis.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 50 mg single dose<br>It includes two group, one group is pilot study, healthy subjects receive a single dose of 50 mg HEC74647PA capsule (N=2) . Another group is formal study, healthy subjects receive a single dose of 50 mg HEC74647PA capsule (N=8) or matching placebo (N=2). | Drug: HEC74647PA Capsule<br>* Capsule administered orally once daily<br>Drug: placebo<br>* Matching Placebo Capsule<br>|
| Experimental: 100 mg single dose<br>Healthy subjects, receiving a single dose of 100 mg HEC74647PA capsule (N=8) or matching placebo (N=2). | Drug: HEC74647PA Capsule<br>* Capsule administered orally once daily<br>Drug: placebo<br>* Matching Placebo Capsule<br>|
| Experimental: 200 mg single dose<br>Healthy subjects, receiving a single dose of 200 mg HEC74647PA capsule (N=16) or matching placebo (N=2) under fed or fasted conditions, this group is a two-sequence, two-period crossover study. | Drug: HEC74647PA Capsule<br>* Capsule administered orally once daily<br>Drug: placebo<br>* Matching Placebo Capsule<br>|
| Experimental: 400 mg single dose<br>Healthy subjects, receiving a single dose of 400 mg HEC74647PA capsule (N=8) or matching placebo (N=2). | Drug: HEC74647PA Capsule<br>* Capsule administered orally once daily<br>Drug: placebo<br>* Matching Placebo Capsule<br>|
| Experimental: 600 mg single dose<br>Healthy subjects, receiving a single dose of 600 mg HEC74647PA capsule (N=8) or matching placebo (N=2). | Drug: HEC74647PA Capsule<br>* Capsule administered orally once daily<br>Drug: placebo<br>* Matching Placebo Capsule<br>|
| Experimental: 800 mg single dose<br>Healthy subjects, receiving a single dose of 800 mg HEC74647PA capsule (N=8) or matching placebo (N=2). | Drug: HEC74647PA Capsule<br>* Capsule administered orally once daily<br>Drug: placebo<br>* Matching Placebo Capsule<br>|
| Experimental: 100 mg multiple doses<br>Healthy subjects, receiving 100 mg HEC74647PA capsule (N=10) or placebo(N=2) once daily (q.d.) for 7 days. | Drug: HEC74647PA Capsule<br>* Capsule administered orally once daily<br>Drug: placebo<br>* Matching Placebo Capsule<br>|
| Experimental: 200 mg multiple doses<br>Healthy subjects, receiving 200 mg HEC74647PA capsule (N=10) or placebo(N=2) once daily (q.d.) for 7 days. | Drug: HEC74647PA Capsule<br>* Capsule administered orally once daily<br>Drug: placebo<br>* Matching Placebo Capsule<br>|
| Experimental: 400 mg multiple doses<br>Healthy subjects, receiving 400 mg HEC74647PA capsule (N=10) or placebo(N=2) once daily (q.d.) for 7 days. | Drug: HEC74647PA Capsule<br>* Capsule administered orally once daily<br>Drug: placebo<br>* Matching Placebo Capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events of the single ascending-dose | To assess the tolerability after a single dose of HEC74647PA capsule | Baseline to day 6 13 | 
| Adverse events of the multiple ascending-dose | To assess the tolerability after multiple doses of HEC74647PA capsule | Baseline to day 12 | 
| Tmax | Time of the maximum observed plasma concentration | Prior to dosing (0 h) and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96 and 120 h after dosing | 
| AUC | Area under the plasma concentration-time curve (AUC) | Prior to dosing (0 h) and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96 and 120 h after dosing | 
| Cmax | Maximum observed plasma concentration of HEC74647 | Prior to dosing (0 h) and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96 and 120 h after dosing | 
| T1/2 | Terminal elimination half-life | Prior to dosing (0 h) and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96 and 120 h after dosing | 
| Vz/F | Apparent volume of distribution | Prior to dosing (0 h) and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96 and 120 h after dosing | 
| CL/F | Oral clearance | Prior to dosing (0 h) and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96 and 120 h after dosing | 
| MRT | Mean Residence Time | Prior to dosing (0 h) and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96 and 120 h after dosing |