NCT07429331

Drug Interaction and Food Effect Study of CS0159

Evaluation of Drug-Drug Interactions Between CS0159 Tablets and Rifampicin/Itraconazole and the Effect of a High-Fat Meal on the Pharmacokinetic Characteristics of CS0159 Tablets in Healthy Adult Participants

• Status: Not Yet Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 32 (estimated)
• Sponsor: Cascade Pharmaceuticals, Inc · Academic / Other
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

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.) .

Detailed description

1. Study Background: CS0159 is a novel farnesoid X receptor agonist under development for the treatment of diseases such as nonalcoholic steatohepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. Preclinical studies indicate that CS0159 is primarily metabolized by the CYP3A4 enzyme. According to relevant guidelines, it is necessary to evaluate the impact of CYP3A4 modulators (rifampicin and itraconazole) on the exposure of CS0159, as well as the effect of food on its pharmacokinetics, to guide safe clinical use. 2. Study Design and Methods: Overall Design: The study consists of two independent parts (Part A and Part B), planning to enroll a total of 32 healthy adult participants (both sexes) aged 18-45. Part A - DDI Study with Rifampicin: A fixed-sequence design is employed. Participants, under fasting conditions, sequentially receive CS0159 monotherapy, rifampicin monotherapy (for 7 consecutive days), and then co-administration of both drugs. Intensive blood sampling is performed for PK analysis. Part B - Food Effect and DDI Study with Itraconazole: Phase 1 (Food Effect): A randomized, open-label, two-period, two-sequence crossover design is used. Participants are randomly divided into two groups to receive a single dose of CS0159 under fasting and high-fat meal conditions, respectively, with a 2-day washout period between the two periods. Phase 2 (DDI Study with Itraconazole): All participants who complete Phase 1 enter this phase. Participants first receive itraconazole after a meal for 5 consecutive days, followed by co-administration of CS0159 with itraconazole after a high-fat meal. Pharmacokinetic and Safety Assessments: Blood samples are collected at scheduled time points during all CS0159 dosing periods (monotherapy or co-administration). CS0159 plasma concentrations are determined using a validated LC-MS/MS method. Throughout the study, adverse events, vital signs, physical examinations, 12-lead ECGs, and laboratory test results are continuously monitored and recorded. 3. Statistical Methods: Pharmacokinetic parameters will be calculated using non-compartmental analysis. For DDI analysis, analysis of variance will be performed on log-transformed C\~max\~ and AUC values, and geometric mean ratios with their 90% confidence intervals will be calculated. Food effect analysis will employ a crossover design analysis of variance. Safety data will be summarized using descriptive statistics.

Conditions

• Healthy Volunteers

Interventions

Type	Name	Description
DRUG	CS0159 Tablet	A novel, selective farnesoid X receptor (FXR) agonist.
DRUG	Rifampicin Capsule	A strong cytochrome P450 3A4 (CYP3A4) enzyme inducer.
DRUG	Itraconazole Capsule	A strong cytochrome P450 3A4 (CYP3A4) enzyme inhibitor.

Timeline

• Start date: 2026-03-01
• Primary completion: 2027-02-01
• Completion: 2027-02-01
• First posted: 2026-02-24
• Last updated: 2026-02-24

Regulatory

• FDA-regulated drug study