Study in Healthy Volunteers to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of CS0159

Study Overview
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Brief Summary
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The whole study includes 2 parts. Both the SAD study and MAD study are randomized, double-blinded, and placebo-controlled studies, conducted in healthy subjects, to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics profiles of CS0159. The SAD part also involves a pilot food effect (FE) study, designed to assess the food effect on single-dose PK profile in healthy subjects.

Detailed Description
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A total of 48 healthy subjects will be allocated to 1 of 6 cohorts (cohort A1 A6) in the SAD study, each cohort including 8 subjects (6 subjects will receive investigational new drug (IND) product and 2 receive placebo). Each subject in fasted state will be randomly assigned to receive a single oral dose of CS0159 or placebo.To ensure the safety for all SAD cohorts (including A3 in both treatment periods). The MAD study will enroll 32 healthy subjects, allocated to 1 of 4 cohorts (cohort B1 B4) and each cohort including 8 participants (6 subjects will receive IND products and 2 receive placebo). Subjects will be randomly assigned to orally receive the IND product or placebo.

Official Title
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A Phase I, Randomized, Double-Blind, Placebo-Contralled, Single Asending Dose / Multiple Ascending Dose Study of CS0159 to to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics, and Effect Food in Healthy Subject

Conditions
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Primary Sclerosing Cholangitis (PSC)

Intervention / Treatment
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* Drug: CS0159


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and non-pregnant female volunteers In good health, determined by having no clinically significant findings from medical history, physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory evaluations Exclusion Criteria: Subjects with special dietary requirements and cannot follow a uniform diet. Pregnant or nursing females or females who have pregnancy plans during the trial or within 3 months after the trial. Any subject with SARS-CoV-2 infection, based on a positive polymerase chain reaction for SARS-CoV-2. History or evidence of clinically significant disorder, condition, or disease that, in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluations, procedures, or completion.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A1: 0.2 mg<br>Participants in fasted state will receive CS0159 0.2 mg or placebo once on Day 1. | Drug: CS0159<br>* Tablets administered orally<br>* Other names: Placebo;|
| Experimental: Cohort A2: 0.6 mg<br>Participants in fasted state will receive CS0159 0.6 mg or placebo once on Day 1. | Drug: CS0159<br>* Tablets administered orally<br>* Other names: Placebo;|
| Experimental: Cohort A3: 1 mg<br>Participants in fasted state will receive CS0159 1 mg or placebo once on Day 1 followed by a 7-day washout period then given in 1 mg tablet (in fed state) on Day 8. | Drug: CS0159<br>* Tablets administered orally<br>* Other names: Placebo;|
| Experimental: Cohort A4: 2 mg<br>Participants in fasted state will receive CS0159 2 mg or placebo once on Day 1. | Drug: CS0159<br>* Tablets administered orally<br>* Other names: Placebo;|
| Experimental: Cohort A5: 4 mg<br>Participants in fasted state will receive CS0159 4 mg or placebo once on Day 1. | Drug: CS0159<br>* Tablets administered orally<br>* Other names: Placebo;|
| Experimental: Cohort A6: 8 mg<br>Participants in fasted state will receive CS0159 8 mg or placebo once on Day 1. | Drug: CS0159<br>* Tablets administered orally<br>* Other names: Placebo;|
| Experimental: Cohort B1: 0.4 mg<br>Participants in fasted state will receive CS0159 0.4 mg or placebo once daily for a consecutive 14 days. | Drug: CS0159<br>* Tablets administered orally<br>* Other names: Placebo;|
| Experimental: Cohort B2: 1 mg<br>Participants in fasted state will receive CS0159 1 mg or placebo once daily for a consecutive 14 days. | Drug: CS0159<br>* Tablets administered orally<br>* Other names: Placebo;|
| Experimental: Cohort B3: 2 mg<br>Participants in fasted state will receive CS0159 2 mg or placebo once daily for a consecutive 14 days. | Drug: CS0159<br>* Tablets administered orally<br>* Other names: Placebo;|
| Experimental: Cohort B4: 4mg<br>Participants in fasted state will receive CS0159 4 mg or placebo once daily for a consecutive 14 days. | Drug: CS0159<br>* Tablets administered orally<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Single-Dose Pharmacokinetic (PK) Parameter | Area under the concentration-time curve (AUC) from time zero to infinity (AUC0-∞) | Day 1 after dosing | 
| Single-Dose Pharmacokinetic (PK) Parameter: (AUC0-last) | AUC from time zero to the time of the last measured concentration | Day 1 after dosing | 
| Single-Dose Pharmacokinetic (PK) Parameter: (Cmax) | Maximum observed plasma concentration | Day 1 after dosing | 
| Single-Dose Pharmacokinetic (PK) Parameter: (Tmax) | Time of the maximum observed plasma concentration | Day 1 after dosing | 
| Multiple-Dose PK Parameter | Maximum concentration during a dosing interval Ct_max | Day 1 after dosing; day 14 | 
| Multiple-Dose PK Parameter: (Ct_min, Day 14) | Minimum concentration during a dosing interval | Day 1 after dosing; day 14 | 
| Multiple-Dose PK Parameter: (AUCtau) | AUC over one dosing interval | Day 1 after dosing; day 14 | 
| To characterize the safety and tolerability of single dose of CS0159 | Incidence and severity of adverse events | up to Day 31 | 
| To characterize the safety and tolerability of multiple doses of CS0159 | Incidence and severity of adverse events | up to Day 44 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamic (PD) Parameter: FGF19 | fibroblast growth factor 19 | Day -1; day 1 | 
| Pharmacodynamic (PD) Parameter: C4 | serum concentration | Day -1; day 1 |