Clinical trial NCT06255951: Studies Evaluating the Effects of Itraconazole or Rifampicin on the Pharmacokinetics of TY-9591 Tablets in Healthy Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: NSCLC
Lead sponsor: TYK Medicines, Inc
Sponsor class: INDUSTRY
First posted: 2024-02-13
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: PartA is the itraconazole study sequence,PartB was the rifampin study sequence.
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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 \&gt; 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.

Primary outcomes:
measure: Peak plasma concentrations (Cmax) of TY-9591 and its metabolites D1 and D2
timeFrame: through study completion,an average of 6 months
measure: Area under the concentration-time curve from 0 to the last quantifiable time point after dose administration (AUC0-t)
timeFrame: through study completion,an average of 6 months
measure: Area under the concentration-time curve from 0 to infinity (AUC0-inf), as data permit
timeFrame: through study completion,an average of 6 months
Secondary outcomes:
measure: Time to peak concentration (Tmax) of TY-9591 and its metabolites D1 and D2
timeFrame: through study completion,an average of 6 months
measure: The half-life of elimination phase (t1/2) of TY-9591 and its metabolites D1 and D2
timeFrame: through study completion,an average of 6 months
measure: elimination rate constant (λz) of TY-9591 and its metabolites D1 and D2
timeFrame: through study completion,an average of 6 months
measure: apparent clearance rate (CL/F) of TY-9591 and its metabolites D1 and D2
timeFrame: through study completion,an average of 6 months
measure: apparent volume of distribution (Vd/F) of TY-9591 and its metabolites D1 and D2
timeFrame: through study completion,an average of 6 months
measure: mean retention time (MRT) of TY-9591 and its metabolites D1 and D2
timeFrame: through study completion,an average of 6 months
measure: Cmax ratio of metabolites to original drug
timeFrame: through study completion,an average of 6 months
measure: AUC ratio of metabolites to original drug
timeFrame: through study completion,an average of 6 months
Other outcomes:
Locations:
city: Guangdong
country: China
facility: Yali Liu
state: Shantou
Study officials:
affiliation: Investigator
name: yali liu
role: PRINCIPAL_INVESTIGATOR
References: