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| Name | Class |
|---|---|
| Covance | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort A1: 0.2 mg | Experimental | Participants in fasted state will receive CS0159 0.2 mg or placebo once on Day 1. |
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| Cohort A2: 0.6 mg | Experimental | Participants in fasted state will receive CS0159 0.6 mg or placebo once on Day 1. |
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| Cohort A3: 1 mg | Experimental | 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. |
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| Cohort A4: 2 mg | Experimental | Participants in fasted state will receive CS0159 2 mg or placebo once on Day 1. |
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| Cohort A5: 4 mg | Experimental | Participants in fasted state will receive CS0159 4 mg or placebo once on Day 1. |
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| Cohort A6: 8 mg | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CS0159 | Drug | Tablets administered orally |
|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacodynamic (PD) Parameter: FGF19 | fibroblast growth factor 19 | Day -1; day 1 |
| Pharmacodynamic (PD) Parameter: C4 | serum concentration |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kathleen Doisy, MD | Labcorp Clinical Research Unit, Inc. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Labcorp Clinical Research Unit, Inc. | Daytona Beach | Florida | 32117 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42271063 | Derived | Zang Y, Shi J, Zhao G, Tang B, Liu M, Yao B, Wang G, Pan H, Yang S, Deng R, Zhao Y, Zhang Z, Guo HR, Sun DD, Wang H, Gao L, Yu J, Diao X, Li Y, Li J, Xu HE. A first-in-class pulsatile FXR agonist for bile-acid-related liver diseases. Nature. 2026 Jun 10. doi: 10.1038/s41586-026-10633-1. Online ahead of print. |
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| ID | Term |
|---|---|
| D015209 | Cholangitis, Sclerosing |
| ID | Term |
|---|---|
| D002761 | Cholangitis |
| D001649 | Bile Duct Diseases |
| D001660 | Biliary Tract Diseases |
| D004066 | Digestive System Diseases |
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Participants in fasted state will receive CS0159 8 mg or placebo once on Day 1.
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| Cohort B1: 0.4 mg | Experimental | Participants in fasted state will receive CS0159 0.4 mg or placebo once daily for a consecutive 14 days. |
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| Cohort B2: 1 mg | Experimental | Participants in fasted state will receive CS0159 1 mg or placebo once daily for a consecutive 14 days. |
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| Cohort B3: 2 mg | Experimental | Participants in fasted state will receive CS0159 2 mg or placebo once daily for a consecutive 14 days. |
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| Cohort B4: 4mg | Experimental | Participants in fasted state will receive CS0159 4 mg or placebo once daily for a consecutive 14 days. |
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| 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 |
| Day -1; day 1 |