Study to Evaluate Safety, Tolerability and Pharmacokinetics and Pharmacodynamics of ASC42 in Healthy Subjects

Study Overview
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Brief Summary
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This is a first in human study of single and multiple ascending doses and food effect of ASC42. This study consists of 8 cohorts and is divided as follows: Part Ia: Single ascending doses study including cohorts 1 to 5. Part Ib: A cross-over design of cohort 2 to study the food effect on ASC42 PK. Part II: Multiple ascending doses study including cohorts 6 to 8.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Dose Escalation, Single Center Phase I Study to Evaluate Safety, Tolerability and Pharmacokinetics and Pharmacodynamics (Biomarkers) of ASC42 in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: ASC42
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Healthy male and female subjects between 18 to 65 years of age. Subjects' weight ≥ 50 kg and BMI within the range of 19 - 29 kg/m2. Physical examination and vital signs are within normal range or slightly abnormal. Key Exclusion Criteria: History or current liver disease, or liver injuries. A positive HBsAg, HCV Ab and/or HIV Ab. Platelet count <150,000/mcL INR> 1.2

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Ascending Dose-ASC42<br>ASC42 tablet，Dose 1，Dose 2，Dose 3，Dose 4，and Dose 5, single dose administration | Drug: ASC42<br>* Oral tablets<br>|
| Experimental: Multiple Ascending Dose-ASC42<br>ASC42 tablet, Dose 1，Dose 2，Dose 3，q.d.×14 days | Drug: ASC42<br>* Oral tablets<br>|
| Placebo Comparator: Single Ascending Dose-Placebo<br>Placebo tablet，Dose 1，Dose 2，Dose 3，Dose 4，and Dose 5, single dose administration | Drug: Placebo<br>* Oral tablets<br>|
| Placebo Comparator: Multiple Ascending Dose-Placebo<br>Placebo tablet，Dose 1，Dose 2，Dose 3，q.d.×14 days | Drug: Placebo<br>* Oral tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Occurrence of Serious Adverse Event (SAE), Adverse Event (AE) resulting in treatment discontinuation and/or dose reductions, and AE of special interest, from baseline up to 21 days | Up to 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC of ASC42 | Evaluate the Area under the plasma concentration versus time curve after single and multiple oral doses of ASC42 administered to healthy volunteers. | On Day 1 to Day 14 after single or multiple doses, respectively. The entire study will last up to 15 days. | 
| Cmax of ASC42 | Evaluate the Peak Plasma Concentration after single and multiple oral doses of ASC42 administered to healthy volunteers. | On Day 1 to Day 14 after single or multiple doses, respectively. The entire study will last up to 15 days. | 
| t1/2 of ASC42 | Evaluate the Terminal-Phase Half-Life after single and multiple oral doses of ASC42 administered to healthy volunteers. | On Day 1 to Day 14 after single or multiple doses, respectively. The entire study will last up to 15 days. | 
| CL/F of ASC42 | Evaluate the Apparent Systemic Clearance after single and multiple oral dose of ASC42 administered to healthy volunteers. | On Day 1 to Day 14 after single or multiple doses, respectively. The entire study will last up to 15 days. | 
| Vd/F of ASC42 | Evaluate the Apparent Volume of Distribution after single and multiple oral dose of ASC42 administered to healthy volunteers. | On Day 1 to Day 14 after single or multiple doses, respectively. The entire study will last up to 15 days. | 
| Tmax of ASC42 | Evaluate the Time to reach the maximum plasma concentration after single single and multiple oral doses of ASC42 administered to healthy volunteers. | On Day 1 to Day 14 after single or multiple doses, respectively. The entire study will last up to 15 days. | 
| C4 | Bile acid precuisor:C4 (7αhydroxy-4-cholesten-3-one) | On Day 1 to Day 14 after single or multiple doses, respectively. The entire study will last up to 15 days. | 
| FGF19 | Bile acid precursor:FGF19 (Fibroblast growth factor 19) | On Day 1 to Day 14 after single or multiple doses, respectively. The entire study will last up to 15 days. |