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

Phase 1

Completed

• Conditions: Primary Sclerosing Cholangitis (PSC)
• Interventions: Drug: CS0159

• Registration Number: NCT05082779
• Lead Sponsor: Cascade Pharmaceuticals, Inc

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2021-09-25
• Status Verified: 2021-10
• Study First Submitted QC: 2021-10-05
• Study First Posted: 2021-10-19
• Study Start: 2021-10-26
• Primary Completion: 2022-09-16
• Study Completion: 2022-10-12
• Last Update Submitted: 2022-10-15
• Last Update Posted: 2022-10-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 79

Inclusion Criteria

1. Healthy male and non-pregnant female volunteers
2. 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

1. Subjects with special dietary requirements and cannot follow a uniform diet.
2. Pregnant or nursing females or females who have pregnancy plans during the trial or within 3 months after the trial.
3. Any subject with SARS-CoV-2 infection, based on a positive polymerase chain reaction for SARS-CoV-2.
4. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort A4: 2 mg	CS0159	Participants in fasted state will receive CS0159 2 mg or placebo once on Day 1.
Cohort A1: 0.2 mg	CS0159	Participants in fasted state will receive CS0159 0.2 mg or placebo once on Day 1.
Cohort A2: 0.6 mg	CS0159	Participants in fasted state will receive CS0159 0.6 mg or placebo once on Day 1.
Cohort A3: 1 mg	CS0159	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.
Cohort B3: 2 mg	CS0159	Participants in fasted state will receive CS0159 2 mg or placebo once daily for a consecutive 14 days.
Cohort B4: 4mg	CS0159	Participants in fasted state will receive CS0159 4 mg or placebo once daily for a consecutive 14 days.
Cohort A5: 4 mg	CS0159	Participants in fasted state will receive CS0159 4 mg or placebo once on Day 1.
Cohort A6: 8 mg	CS0159	Participants in fasted state will receive CS0159 8 mg or placebo once on Day 1.
Cohort B1: 0.4 mg	CS0159	Participants in fasted state will receive CS0159 0.4 mg or placebo once daily for a consecutive 14 days.
Cohort B2: 1 mg	CS0159	Participants in fasted state will receive CS0159 1 mg or placebo once daily for a consecutive 14 days.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Pharmacodynamic (PD) Parameter: C4	Day -1; day 1	serum concentration
Pharmacodynamic (PD) Parameter: FGF19	Day -1; day 1	fibroblast growth factor 19

Trial Locations

Locations (1)

Labcorp Clinical Research Unit, Inc.; 🇺🇸 Daytona Beach, Florida, United States