Studies Evaluating the Effects of Itraconazole or Rifampicin on the Pharmacokinetics of TY-9591 Tablets in Healthy Subjects

This is a Single-center, Two-sequence, Open-label, Two-cycle Drug-drug Interaction (DDI) Study in Healthy Subjects. To Evaluate the Effects of Itraconazole Capsules, a Strong Inhibitor of CYP3A4, and Rifampicin Capsules, a Strong Inducer, on the Pharmacokinetics of TY-9591 Tablets After a Single Oral Dose

Studies evaluating the effects of itraconazole or rifampicin on the pharmacokinetics of TY-9591 tablets in healthy subjects

Study Overview

• Status: Recruiting
• Conditions: NSCLC
• Intervention / Treatment: Drug: Itraconazole; Drug: Rifampicin

Detailed Description

To evaluate the pharmacokinetics of TY-9591 tablets in healthy Chinese subjects after a single oral administration. To evaluate the effects of itraconazole/rifampicin on the pharmacokinetics of TY-9591 and its metabolites D1 and D2 after oral administration of TY-9591 tablets.

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yali Liu; Phone Number: 0754-88258290; Email: fuyiyuanban@163.com
• Study Contact Backup: Name: Yali Liu; Phone Number: 075488258290; Email: fuyiyuanban@163.com

Study Locations

• China
  • Shantou
    • Guangdong, Shantou, China, 515041
      • Recruiting
      • Yali Liu
      • Contact: liu yali; Phone Number: 0754-88258290; Email: fuyiyuanban@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female healthy adult subjects aged 18-45 years old (inclusive), in which male or female accounted for no less than 1/4 of the total number of subjects in each sequence.
2. Body mass index (BMI) between 19.0 and 26.0 kg/m2 [BMI= weight (kg)/ height 2 (m2)] (including boundary values).
3. Participants (including male participants) were infertile themselves, or agreed to use highly effective nonpharmacologic contraceptive methods or abstain completely from sex for 6 months after the last dose of self-medication.
4. Subjects voluntarily participated and signed an informed consent form.
5. Subjects had good communication with investigators and were able to complete the trial in accordance with the protocol.

Exclusion Criteria:

1. Those with clinically significant abnormalities in physical examination, vital signs, routine laboratory tests (blood routine, urine routine, blood biochemistry, coagulation function), 12-lead electrocardiogram, ophthalmic examination, abdominal color Doppler ultrasound (liver, bile duct, pancreas, spleen, kidney), etc.
2. Persons with one or more positive results of human immunodeficiency virus (HIV) antibody, hepatitis B virus surface antigen (HBsAg) or hepatitis C virus (HCV) antibody, or treponema pallidum antibody (Anti-TP).
3. smokers with an average of more than 10 cigarettes per day in the previous 3 months or habitual users of nicotine products who could not quit during the study.
4. Heavy drinking or regular drinking in the 3 months before the screening period, i.e. drinking more than 14 units of alcohol per week (1 unit =360 mL of beer or 45 mL of 40% spirits or 150 mL of wine); Or alcohol breath test results on admission > 0.0 mg/100 mL and those who could not abstain from alcohol during the experiment.
5. those who consumed excessive amounts of tea, coffee, and/or caffeinated beverages (average > 8 cups/day, 250 mL/cup) in the 3 months before the screening period, and those who could not stop using them during the study period.
6. those who took dragon fruit, mango, grapefruit, chocolate, any food or beverage containing caffeine, diet rich in xanthine, and other special diets affecting drug absorption, distribution, metabolism, and excretion within 7 days before taking the drug.
7. Use of any drugs that inhibit or induce the liver CYP3A4 enzyme (see Appendix II), herbs, or foods containing herbal ingredients within 30 days before the screening period.
8. taking any medicine (including Chinese herbal medicine and health supplements) within 14 days before taking the test drug.
9. enrollment in any drug clinical trial within 3 months before the screening period.
10. Subjects who may not be able to complete the study for other reasons or who are considered unsuitable for the study by the investigators.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Itraconazole	Drug: Itraconazole; The study was divided into two sequences with a planned enrollment of 48 healthy adult subjects (24 in each sequence). PartA was the itraconazole study sequence, which was used to study the effect of itraconazole on the pharmacokinetic characteristics of TY-9591 tablets after multiple doses.
Experimental: Rifampicin	Drug: Rifampicin; The study was divided into two sequences with a planned enrollment of 48 healthy adult subjects (24 in each sequence). PartB was the rifampin study sequence, which investigated the effect of multiple doses of rifampin on the pharmacokinetic profile of TY-9591 tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak plasma concentrations (Cmax) of TY-9591 and its metabolites D1 and D2	Peak plasma concentrations (Cmax) of TY-9591 and its metabolites D1 and D2	through study completion,an average of 6 months
Area under the concentration-time curve from 0 to the last quantifiable time point after dose administration (AUC0-t)	Area under the concentration-time curve from 0 to the last quantifiable time point after dose administration (AUC0-t)	through study completion,an average of 6 months
Area under the concentration-time curve from 0 to infinity (AUC0-inf), as data permit	Area under the concentration-time curve from 0 to infinity (AUC0-inf), as data permit	through study completion,an average of 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to peak concentration (Tmax) of TY-9591 and its metabolites D1 and D2	Time to peak concentration (Tmax) of TY-9591 and its metabolites D1 and D2	through study completion,an average of 6 months
The half-life of elimination phase (t1/2) of TY-9591 and its metabolites D1 and D2	The half-life of elimination phase (t1/2) of TY-9591 and its metabolites D1 and D2	through study completion,an average of 6 months
elimination rate constant (λz) of TY-9591 and its metabolites D1 and D2	elimination rate constant (λz) of TY-9591 and its metabolites D1 and D2	through study completion,an average of 6 months
apparent clearance rate (CL/F) of TY-9591 and its metabolites D1 and D2	apparent clearance rate (CL/F) of TY-9591 and its metabolites D1 and D2	through study completion,an average of 6 months
apparent volume of distribution (Vd/F) of TY-9591 and its metabolites D1 and D2	apparent volume of distribution (Vd/F) of TY-9591 and its metabolites D1 and D2	through study completion,an average of 6 months
mean retention time (MRT) of TY-9591 and its metabolites D1 and D2	mean retention time (MRT) of TY-9591 and its metabolites D1 and D2	through study completion,an average of 6 months
Cmax ratio of metabolites to original drug	Cmax ratio of metabolites to original drug	through study completion,an average of 6 months
AUC ratio of metabolites to original drug	AUC ratio of metabolites to original drug	through study completion,an average of 6 months

Collaborators and Investigators

• Sponsor: TYK Medicines, Inc
• Investigators: Principal Investigator: yali liu, Investigator

Study record dates

Study Major Dates

• Study Start (Estimated): March 4, 2024
• Primary Completion (Estimated): July 8, 2024
• Study Completion (Estimated): August 5, 2024

Study Registration Dates

• First Submitted: January 17, 2024
• First Submitted That Met QC Criteria: February 3, 2024
• First Posted (Actual): February 13, 2024

Study Record Updates

• Last Update Posted (Estimated): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 22, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Leprostatic Agents; Hormone Antagonists; Cytochrome P-450 Enzyme Inducers; Antifungal Agents; Steroid Synthesis Inhibitors; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; 14-alpha Demethylase Inhibitors; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Rifampin; Itraconazole
• Other Study ID Numbers: TYKM1601105

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