Drug Interaction and Food Effect Study of CS0159

NCT07429331 | Completed Phase 1 FDA Drug

• 1 other identifier: CS0159-DDI-CN-I-08
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Purpose: This study aims to evaluate the effect of food (high-fat, high-calorie meal) on the pharmacokinetic (PK) profile of CS0159 tablets and to assess the drug-drug interactions (DDI) when CS0159 is co-administered with a strong CYP3A4 inducer (rifampicin) and a strong CYP3A4 inhibitor (itraconazole), respectively. Design: Part A (DDI - Induction): Single-center, open-label, fixed-sequence design. Sixteen healthy participants will receive a single dose of CS0159 (4 mg) under fasting conditions on Day 1, rifampicin alone (600 mg, QD) under fasting conditions on Days 2-8, and co-administration of CS0159 with rifampicin under fasting conditions on Day 9. Part B (Food Effect \& DDI - Inhibition): Single-center, open-label, two-phase design. Sixteen healthy participants will first undergo a randomized, two-period, two-sequence crossover food effect study (CS0159 4 mg administered under fasting vs. high-fat meal conditions). All participants will then enter the second phase, receiving itraconazole (200 mg, QD) after a meal for 5 consecutive days, followed by co-administration of CS0159 with itraconazole after a high-fat meal on the 6th day. Endpoints: The primary endpoints are the pharmacokinetic parameters of CS0159 (C\~max, AUC\~0-t, AUC\~0-∞)and other PK parameters (Tmax，t1/2，λz，AUC\_%Extrap，Tlag，CL/F，V/F). Secondary endpoints include safety (adverse events, vital signs, laboratory tests, etc.) .

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (6)

• Cmax of CS0159

  Maximum observed plasma concentration (Cmax) of CS0159

  Day 1, Day 3, Day 9

• AUC0-t of CS0159

  Area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC0-t) of CS0159

  Day 1, Day 3, Day 9

• AUC0-∞ of CS0159

  Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC0-∞) of CS0159

  Day 1, Day 3, Day 9

• Tmax of CS0159

  Time to reach Cmax (Tmax)

  Day 1, Day 3, Day 9

• t1/2 of CS0159

  terminal elimination half-life (t1/2)

  Day 1, Day 3, Day 9

• CL/F of CS0159

  apparent oral clearance (CL/F)

  Day 1, Day 3, Day 9

Secondary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events (TEAEs)

  From screening until 7 days after the last dose.

Study Arms (3)

Part A: CS0159 + Rifampicin (DDI)

EXPERIMENTAL

Healthy participants receive a single oral dose of CS0159 (4 mg) under fasting conditions on Day 1, followed by oral rifampicin (600 mg) once daily under fasting conditions on Days 2-8, and then co-administration of both drugs under fasting conditions on Day 9.

Drug: CS0159 Tablet; Drug: Rifampicin Capsule

Part B: CS0159 (Food Effect)

EXPERIMENTAL

The 16 enrolled participants are randomly assigned to two groups (fasting-fed group and fed-fasting group) in Phase 1, with an equal number in each group. Each group receives a single 4 mg dose per period, with a 2-day washout period (in-house).

Drug: CS0159 Tablet

Part B: CS0159 + Itraconazole (DDI)

EXPERIMENTAL

Healthy participants receive oral itraconazole capsules (200 mg, two capsules of 0.1 g each) once daily in the morning under fed conditions (following a standard meal) from Day 4 to Day 8 (D4\~D8), which corresponds to days 2 to 6 after completing the second period of Phase 1. This constitutes 5 consecutive days of itraconazole administration. On the 6th administration day (D9), participants simultaneously take itraconazole capsules (200 mg) and CS0159 tablets (4 mg, two tablets of 2 mg each) under fed conditions (following a high-fat meal).

Drug: CS0159 Tablet; Drug: Itraconazole Capsule

Interventions

CS0159 Tablet DRUG

A novel, selective farnesoid X receptor (FXR) agonist.

Also known as: Investigational drug (FXR agonist)

Part A: CS0159 + Rifampicin (DDI); Part B: CS0159 (Food Effect); Part B: CS0159 + Itraconazole (DDI)

Rifampicin Capsule DRUG

A strong cytochrome P450 3A4 (CYP3A4) enzyme inducer.

Also known as: CYP3A4 inducer (perpetrator drug)

Part A: CS0159 + Rifampicin (DDI)

Itraconazole Capsule DRUG

A strong cytochrome P450 3A4 (CYP3A4) enzyme inhibitor.

Also known as: CYP3A4 inhibitor (perpetrator drug)

Part B: CS0159 + Itraconazole (DDI)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male or female participants aged between 18 and 45 years (inclusive);
• Male weight ≥ 50.0 kg, female weight ≥ 45.0 kg; body mass index (BMI) within the range of 19.0 to 26.0 kg/m² (including the threshold values);
• Normal renal function (glomerular filtration rate calculated using the CKD-EPI equation ≥ 90 mL/min/1.73 m²);
• Participants (including male participants) agree to have no plans for conception from screening until 3 months after the last dose, voluntarily adopt effective contraceptive measures, and have no plans for sperm or egg donation;
• Participants fully understand the study purpose, nature, procedures, and potential adverse events, voluntarily agree to participate as subjects, can communicate well with the investigator, comply with all study requirements, and sign the informed consent form before the initiation of any study procedures.

You may not qualify if:

• History of allergic diseases (e.g., asthma, urticaria, eczema, etc.), allergic constitution (e.g., allergy to two or more drugs), or known hypersensitivity to CS0159, rifampicin, itraconazole, or any excipients;
• Participants with clinically significant findings, as judged by the investigator, of the following diseases (including but not limited to gastrointestinal, renal, hepatic, neurological, hematological, endocrine, oncological, pulmonary, immunological, psychiatric, or cardiovascular/cerebrovascular diseases) that may complicate protocol implementation or interpretation of study results, or whom the investigator considers to be at risk from participating in the study;
• History of susceptibility to pruritus, or presence of conditions such as eczema/atopic dermatitis, neurodermatitis, psoriasis, or other diseases that may cause pruritus;
• History of corrected QT interval (QTc) prolongation at screening:
• QTc interval prolongation on 12-lead electrocardiogram (ECG) (QTcF ≥450 ms in males; QTcF ≥470 ms in females);
• Family history of hypocalcemia or long QT syndrome.
• History of acute or chronic bronchospasm (including treated or untreated asthma, chronic obstructive pulmonary disease);
• Occurrence of an acute illness within 2 weeks prior to the first dose;
• Presence of any known disease or condition that may interfere with drug absorption, distribution, metabolism, or excretion, including bile salt metabolism in the large intestine. Examples include inflammatory bowel disease, gastrectomy, cholecystectomy, etc.;
• Use of drugs affecting hepatic metabolic enzyme function (e.g., barbiturates, carbamazepine, phenytoin, glucocorticoids, omeprazole, SSRIs, cimetidine, diltiazem, macrolides, nitroimidazoles, sedative-hypnotics, verapamil, fluoroquinolones, antihistamines) within 30 days prior to the first dose, or requirement for concomitant use of other drugs that may affect the absorption, distribution, metabolism, or excretion of the investigational drug during the study period;
• History of blood donation within 3 months prior to the first dose, total blood loss ≥400 mL due to donation or other reasons within 6 months, or plans to donate blood during the study or within 3 months after study completion;
• Current smokers, or participants unwilling to discontinue nicotine product use from 3 months before screening and during the study, or with positive urine cotinine test results;
• Excessive consumption of tea, coffee, or caffeinated beverages (more than 8 cups per day, 1 cup = 250 mL) within 6 months prior to screening; or consumption of any food or beverage rich in caffeine and/or xanthine (e.g., coffee, strong tea, chocolate, caffeinated carbonated beverages, cola, etc.) from 48 hours before the first dose until the end of the study; or unwillingness to abstain from alcohol, fruit juice beverages, strenuous exercise, or other factors that may affect drug absorption, distribution, metabolism, or excretion;
• Average weekly alcohol consumption exceeding 14 units (1 unit = 360 mL beer, 45 mL of 40% alcohol liquor, or 150 mL wine) in the past year, or inability to abstain from alcohol during the study, or alcohol breath test result \>0.0 mg/100 mL;
• Drug abusers or participants with positive results on drug abuse screening (morphine, tetrahydrocannabinol acid, methamphetamine, methylenedioxymethamphetamine, ketamine, and cocaine);

Sponsors & Collaborators

• Cascade Pharmaceuticals, Inc: lead

Study Sites (1)

Shanghai Xuhui Central Hospital

Shanghai, Shanghai Municipality, China

Location

MeSH Terms

Interventions

Drugs, Investigational; Rifampin; Cytochrome P-450 CYP3A Inducers; Itraconazole; Cytochrome P-450 CYP3A Inhibitors

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Cytochrome P-450 Enzyme Inducers; Metabolic Side Effects of Drugs and Substances; Pharmacologic Actions; Chemical Actions and Uses; Molecular Mechanisms of Pharmacological Action; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Piperazines; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors

Study Officials

• Yun Liu

  Shanghai Xuhui District Central Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label study. No blinding was used.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a two-part, hybrid-design pharmacokinetic study: 1. Part A (n=16): A single-group, fixed-sequence study. All participants receive CS0159 monotherapy (Day 1), followed by rifampicin alone (Days 2-8), and then co-administration of both drugs (Day 9) to assess the inducing effect of rifampicin on CS0159. 2. Part B (n=16): This part consists of two sequential phases within the same cohort: * Phase 1 (Food Effect):\*\* A randomized, two-period, two-sequence crossover study. Participants are randomized to receive CS0159 either under fasting conditions or after a high-fat meal in the first period, and then cross over to the opposite condition in the second period after a washout. * Phase 2 (DDI with Itraconazole):\*\* Following Phase 1, all participants enter a single-group, fixed-sequence study. They receive itraconazole alone for 5 days, followed by co-administration of CS0159 with itraconazole to assess the inhibitory effect.

Study Record Dates

• First Submitted: February 9, 2026
• First Posted: February 24, 2026
• Study Start: March 9, 2026
• Primary Completion: March 25, 2026
• Study Completion: April 1, 2026
• Last Updated: June 3, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)