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

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

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.

Study Overview

• Status: Completed
• Conditions: Primary Sclerosing Cholangitis (PSC)
• Intervention / Treatment: Drug: CS0159

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 Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Labcorp Clinical Research Unit, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A1: 0.2 mg; Participants in fasted state will receive CS0159 0.2 mg or placebo once on Day 1.	Drug: CS0159; Tablets administered orally; Other Names: Placebo
Experimental: Cohort A2: 0.6 mg; Participants in fasted state will receive CS0159 0.6 mg or placebo once on Day 1.	Drug: CS0159; Tablets administered orally; Other Names: Placebo
Experimental: Cohort A3: 1 mg; 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; Tablets administered orally; Other Names: Placebo
Experimental: Cohort A4: 2 mg; Participants in fasted state will receive CS0159 2 mg or placebo once on Day 1.	Drug: CS0159; Tablets administered orally; Other Names: Placebo
Experimental: Cohort A5: 4 mg; Participants in fasted state will receive CS0159 4 mg or placebo once on Day 1.	Drug: CS0159; Tablets administered orally; Other Names: Placebo
Experimental: Cohort A6: 8 mg; Participants in fasted state will receive CS0159 8 mg or placebo once on Day 1.	Drug: CS0159; Tablets administered orally; Other Names: Placebo
Experimental: Cohort B1: 0.4 mg; Participants in fasted state will receive CS0159 0.4 mg or placebo once daily for a consecutive 14 days.	Drug: CS0159; Tablets administered orally; Other Names: Placebo
Experimental: Cohort B2: 1 mg; Participants in fasted state will receive CS0159 1 mg or placebo once daily for a consecutive 14 days.	Drug: CS0159; Tablets administered orally; Other Names: Placebo
Experimental: Cohort B3: 2 mg; Participants in fasted state will receive CS0159 2 mg or placebo once daily for a consecutive 14 days.	Drug: CS0159; Tablets administered orally; Other Names: Placebo
Experimental: Cohort B4: 4mg; Participants in fasted state will receive CS0159 4 mg or placebo once daily for a consecutive 14 days.	Drug: CS0159; Tablets administered orally; Other Names: Placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Cascade Pharmaceuticals, Inc
• Collaborators: Covance
• Investigators: Principal Investigator: Kathleen Doisy, MD, Labcorp Clinical Research Unit, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2021
• Primary Completion (Actual): September 16, 2022
• Study Completion (Actual): October 12, 2022

Study Registration Dates

• First Submitted: September 25, 2021
• First Submitted That Met QC Criteria: October 5, 2021
• First Posted (Actual): October 19, 2021

Study Record Updates

• Last Update Posted (Actual): October 18, 2022
• Last Update Submitted That Met QC Criteria: October 15, 2022
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholangitis; Cholangitis, Sclerosing
• Other Study ID Numbers: CS0159-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No