A First in Human Study to Evaluate Safety, Tolerability, Pharmacology of HS-10374 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, and pharmacokinetics (PK) of HS-10374 in healthy subjects.

Official Title
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A Phase 1, Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of HS-10374 in Healthy Subjects

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: HS-10374 tablets
* Drug: HS-10374-matched placebo tablets


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 of contraception, and refrain from donating sperm or eggs during the study period and for at least 6 months after last dosing Have signed the informed consent form approved by the IRB Exclusion Criteria: Have a clinically significant infection currently or within past 30 days, or have a history of active tuberculosis; or have positive screening test for infectious disease, including tuberculosis, 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 or drugs of abuse Smokers smoked ≥5 cigarettes per day within past 3 months or have a positive test result for nicotine Clinically significant abnormal physical examination, vital signs, clinical laboratory values, ECGs or imaging tests Pregnant or breastfeeding female subjects Have received hormone-based contraceptives, drugs that prolong the QT interval, drugs that may cause drug interactions with investigational product, immunosuppressants, vaccines or other drugs within a specific period

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-10374<br>Single and multiple ascending doses of HS-10374 orally | Drug: HS-10374 tablets<br>* Single or multiple dosing of HS-10374 orally in a fasting state<br>|
| Placebo Comparator: Placebo<br>Single and multiple ascending doses of HS-10374-matched placebo orally | Drug: HS-10374-matched placebo tablets<br>* Single or multiple dosing of HS-10374-matched placebo orally in a fasting state<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 42 (MAD) | 
| Number of participants with clinical laboratory abnormalities | Clinical laboratory tests include hematology, urinalysis, stool analysis, blood chemistry, coagulation testing, Cystatin C, urine β2-microglobulin, erythrocyte sedimentation rate, C-reactive protein, etc. | Day 1 up to Day 12 (SAD), Day 1 up to Day 42 (MAD) | 
| Number of participants with abnormalities of vital signs | Vital sign measured include blood pressure, pulse rate, temperature, and respiration rate. | Day 1 up to Day 12 (SAD), Day 1 up to Day 42 (MAD) | 
| Number of participants with abnormalities of physical examination | Physical examination includes assessments of general appearance, skin, lymph nodes, head, neck, lung, heart, abdomen, spine, extremities, nervous system, etc. | Day 1 up to Day 12 (SAD), Day 1 up to Day 42 (MAD) | 
| Number of participants with abnormalities of electrocardiogram (ECG) parameters | ECG parameters include heart rate, PR interval, RR interval, QRS duration, QTcF interval. | Day 1 up to Day 12 (SAD), Day 1 up to Day 42 (MAD) | 

Secondary Outcome Measures

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