Phase I Study to Evaluate Safety, Tolerability, and Pharmacokinetics of HS-10360 in Healthy Subjects.

Study Overview
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Brief Summary
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The primary objective of this study is to assess the safety and tolerability of single and multiple oral administered doses of HS-10360 in healthy subjects.

Detailed Description
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This is a phase I, randomized, double-blinded, placebo-controlled, single ascending doses (SAD) study followed by multiple ascending doses (MAD) clinical trial to assess the safety, tolerability, and pharmacokinetics of HS-10360 tablet (s) in Chinese healthy adult subjects. Approximately five sequential dose levels will be evaluated in SAD phase. Two sentinel subjects will be enrolled in the first cohort and minimal 72 hours post-dose safety data will be evaluated before the remaining subjects are enrolled in this cohort. Approximately three sequential dose cohorts (the specific dose levels should be further determined according to the SAD results) will be evaluated in MAD phase. Each subject will receive only one dose regimen in this study. Safety data up to Day12 (±2) in SAD and up to Day28 (±2) in MAD will be reviewed prior to the next dose level. The number of Cohorts in SAD and MAD would be adjusted based on the assessment of SRC.

Official Title
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A Phase I, Randomized, Double-blinded, Placebo-controlled Dose Escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of Oral Administered HS-10360 in Healthy Subjects.

Conditions
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Healthy

Intervention / Treatment
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* Drug: HS-10360
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must meet all of the following inclusion criteria to be eligible for participation in this study: Healthy male or female subjects between 18 and 45 years old; Body weight more than 50.0kg (male) or 45.0kg (female), body mass index (BMI) within the range of 19.0 26.0kg/m2 (both inclusive); Subjects and their partners should have no fertility plan, no sperm or ootid donation plan and must use highly effective contraceptive methods (such as abstinence, condom, etc.) from the screening period to 6 months post-trial; Additional inclusion criteria apply; Exclusion Criteria: A subject will not be eligible for inclusion in this study if any of the following criteria apply: Clinically significant abnormalities in baseline results of laboratory evaluations; Subjects has a positive result of any of following virology tests (hepatitis B surface antigen HBsAg, hepatitis B core antibody HBcAb, hepatitis C virus HCV antibody, human immunodeficiency virus HIV antibody, Treponema pallidum antibody TP-Ab) ; History or evidence of clinically significant cardiovascular, pulmonary, endocrine, gastrointestinal, psychiatric, neurologic, hematological or metabolic diseases, especially those conditions that interfere with absorption, metabolism and/or excretion of the study drug, determined by the investigator; Any previous or current severe infection, such as cellulitis, pneumonia, sepsis etc., requiring hospitalization and/or intravenous antibiotic treatment, within 30 prior to the screening period; Have participated in clinical trials of other drugs or medical devices within 3 months or within 5 half-lives of other drugs before screening (if 5 half-lives exceed 3 months); History or presence of allergy, especially known allergy to investigational product components or other JAK inhibitors; Had taken any medication, including prescription, over-the-counter, herbal, dietary supplements, or vaccines, within the previous 2 weeks; or within the five half-lives of the aforementioned drugs prior to randomization;

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-10360<br>Either single or multiple doses of varying dose levels | Drug: HS-10360<br>* Single or multiple dose(s) of HS-10360<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Single or multiple dose(s) of Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-emergent adverse events (TEAE) | Number of participants who experience one or more treatment-emergent adverse events (TEAE) | Baseline to end of follow-up (a maximum of 42 days) | 
| Moderate or severe treatment-emergent adverse events (TEAE) | Number of participants who experience one or more moderate or severe treatment-emergent adverse events (TEAE) | Baseline to end of follow-up (a maximum of 42 days) | 
| Serious treatment-emergent adverse events (TEAE) | Number of participants who experience one or more serious treatment-emergent adverse events (TEAE) | Baseline to end of follow-up (a maximum of 42 days) | 
| Clinical laboratory measurements | Number of participants who experienced a clinically significant clinical laboratory measurements | Baseline to end of follow-up (a maximum of 42 days) | 
| Electrocardiogram | Number of participants who experienced a clinically significant electrocardiogram (ECG) result | Baseline to end of follow-up (a maximum of 42 days) | 
| Vital Signs | Number of participants who experienced a clinically significant vital sign measurement | Baseline to end of follow-up (a maximum of 42 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SAD pharmacokinetic endpoints: | The maximum plasma concentration (Cmax) | Day1-Day6 | 
| SAD pharmacokinetic endpoints: | Time to Cmax (Tmax) | Day1-Day6 | 
| SAD pharmacokinetic endpoints: | The area under the plasma concentration-time curve from time zero to the time of the last measurable concentration (AUC0-t) | Day1-Day6 | 
| SAD pharmacokinetic endpoints: | The area under the plasma concentration-time curve from time zero xtrapolated to infinite time (AUC0-∞) | Day1-Day6 | 
| SAD pharmacokinetic endpoints: | Terminal rate constant (λz) | Day1-Day6 | 
| SAD pharmacokinetic endpoints: | Half life (t½) | Day1-Day6 | 
| SAD pharmacokinetic endpoints: | Apparent clearance following oral administration (CL/F) | Day1-Day6 | 
| SAD pharmacokinetic endpoints: | Apparent volume of distribution following oral administration (Vz/F) | Day1-Day6 | 
| SAD pharmacokinetic endpoints: | Mean residence time (MRT) | Day1-Day6 | 
| SAD pharmacokinetic endpoints: | Amount excreted in urine (Aeu) | Day1-Day6(SAD) | 
| SAD pharmacokinetic endpoints: | Amount excreted in feces (Aef) | Day1-Day6(SAD) | 
| MAD pharmacokinetic endpoints: | The maximum steady state drug concentration in plasma during dosing interval (Css,max) | Day1-Day19 | 
| MAD pharmacokinetic endpoints: | The minimum steady state drug concentration in plasma during dosing interval (Css,min) | Day1-Day19 | 
| MAD pharmacokinetic endpoints: | Average steady state drug concentration in plasma during dosing interval Css,av) | Day1-Day19 | 
| MAD pharmacokinetic endpoints: | Time to Css, max (Tss,max) | Day1-Day19 | 
| MAD pharmacokinetic endpoints: | The area under the plasma concentration-time curve over the dosing interval at steady state (AUCss) | Day1-Day19 | 
| MAD pharmacokinetic endpoints: | The area under the plasma concentration-time curve from time zero to the time of the last measurable concentration at steady state(AUC0-t) | Day1-Day19 | 
| MAD pharmacokinetic endpoints: | The area under the plasma concentration-time curve from time zero xtrapolated to infinite time (AUC0-∞) at steady state | Day1-Day19 | 
| MAD pharmacokinetic endpoints: | Half life (t½) | Day1-Day19 | 
| MAD pharmacokinetic endpoints: | Accumulation ratio (Rac) | Day1-Day19 | 
| MAD pharmacokinetic endpoints: | Apparent clearance at steady state following oral administration (CLss/F) | Day1-Day19 | 
| MAD pharmacokinetic endpoints: | Apparent volume of distribution at steady state following oral administration (Vd/F) | Day1-Day19 | 
| MAD pharmacokinetic endpoints: | Amount excreted in urine (Aeu) | Day1-Day19 | 
| MAD pharmacokinetic endpoints: | Amount excreted in feces (Aef) | Day1-Day19 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HS-10360; Safety; Pharmacokinetics