A First in Human Study to Evaluate Safety, Tolerability, Pharmacology of HS-10390 in Healthy Subjects

Study Overview
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Brief Summary
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The purpose of this first in human study is to evaluate the safety, tolerability, pharmacokinetics (PK),and pharmacodynamics (PD) of HS-10390 in healthy subjects.

Detailed Description
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This is a Phase 1, randomized, double-blind, placebo-controlled, single and multiple ascendingdose (SAD and MAD) study to evaluate the safety, tolerability, PK, and PD of different doses of HS-10390 tablet(s) in healthy subjects. During the SAD and MAD periods, there will be approximately 6and 3 sequential cohorts respectively. A sentinel dosing strategy will be used in the first cohort ofSAD. The MAD study will start after sufficient safety and PK data of SAD period are obtained.

Official Title
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A Phase 1, Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Studyto Evaluate the Safety, Tolerability and Pharmacokinetics of HS-10390 in Healthy Subjects

Conditions
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IgA Nephropathy, Focal Segmental Glomerulosclerosis

Intervention / Treatment
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* Drug: HS-10390 tablet
* Drug: Placebo tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female subjects between the ages of 18-45 years Have no reproductive potential; or agree to use a highly effective method ofcontraception, and refrain from donating sperm or eggs during the study period and forat least 6 months after last dosing Have signed the informed consent form approved by the IRB Exclusion Criteria: History or evidence of clinically significant cardiovascular, pulmonary, endocrine,gastrointestinal, psychiatric, neurologic, hematological or metabolic diseases, especiallythose conditions that interfere with absorption, metabolism and/or excretion of the studydrug, determined by the investigator Have a clinically significant infection currently or within past 30 days, or have a history ofactive tuberculosis; or have positive screening test for infectious disease, includingtuberculosis, viral hepatitis, AIDS and syphilis Have a history of or current allergic disease Have a history of drug or alcohol abuse or currently positive test result(s) for alcohol ordrugs of abuse Smokers smoked ≥5 cigarettes per day within past 3 months or have a positive test resultfor nicotine Clinically significant abnormal physical examination, vital signs, clinical laboratory values,ECGs or imaging tests Pregnant or breastfeeding female subjects

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HS-10390<br>Single or multiple dosing of HS-10390 in a fastingstate | Drug: HS-10390 tablet<br>* Oral administration of specified dose of HS-10390<br>|
| Experimental: Placebo<br>Single or multiple dosing of placebo in a fastingstate | Drug: Placebo tablet<br>* Oral administration of matching dose ofplacebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence, severity and association with the study drug of adverse events (AEs), serious AEs (SAEs), and AEs leading to discontinuation |  | Day 1 up to Day 12 (SAD), Day 1 up to Day 28 (MAD) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) |  | Day 1 up to Day 6 (SAD), Day 1 up to Day 19 (MAD) | 
| Time to reach Cmax (Tmax) |  | Day 1 up to Day 6 (SAD), Day 1 up to Day 19 (MAD) | 
| Area under the plasma concentration-time curve from time zero to time t (AUC0-t) |  | Day 1 up to Day 6 (SAD), Day 1 up to Day 19 (MAD) | 
| Half time (t½) |  | Day 1 up to Day 6 (SAD), Day 1 up to Day 19 (MAD) | 
| Apparent clearance (CL/F) |  | Day 1 up to Day 6 (SAD), Day 1 up to Day 19 (MAD) | 
| Apparent volume of distribution (Vz/F) |  | Day 1 up to Day 6 (SAD), Day 1 up to Day 19 (MAD) | 
| Accumulation ratio（Rac） |  | Day 14 up to Day 19 (MAD) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HS-10390, Safety, Tolerability, Pharmacokinetics, Pharmacodynamics