Clinical trial NCT05631678: Drug-drug Interaction Study Beteewn ASK120067 and Rifampicin or Itraconazole
Official title: An Open-lable, Two- Period, Single-sequence, Self-controlled Study to Evaluate the Effect of Oral Rifampicin or Itraconazole on the Pharmacokinetics of ASK120067 Tablets
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Locally Advanced or Metastatic NSCLC
Lead sponsor: Jiangsu Aosaikang Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-11-30
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the effects of oral administration rifampicin or itraconazole capsules on the pharmacokinetics of ASK120067 and its metabolite CCB4580030 in healthy subjects.

To evaluate the safety of ASK120067 tablets or combination with rifampicin capsules or itraconazole capsules in healthy subjects.


Eligibility criteria: Inclusion Criteria:

1. healthy adult subjects, male and female;
2. Age: 18-45 years old (including boundary value);
3. Body weight: body mass index (BMI) between 18.5 and 26.0 kg/m2 (including boundary values);
4. Subjects are willing to sign the informed consent;
5. Subjects are able to communicate well with investigators and complete the clinical trial in according to the protocol.

Exclusion Criteria:

1. patients with clinical significance who are abnormal by comprehensive physical examination, vital signs examination, routine laboratory examination (blood routine, urine routine, blood biochemistry, coagulation function), 12-lead electrocardiogram, and positive and lateral chest radiographs;
2. HBSAg HCVAb HIVAb, and treponema palliatum antibody test results were positive;
3. taking any drugs that inhibit or induce hepatic metabolism of drugs (especially CYP3A4, CYP2C8, CYP2C9 and CYP2C19) within 30 days before the screening period (e.g., inducers - barbiturates, carbamazepine, phenytoin, rifampicin, glucocorticoids, rifabutin, PPI inhibitors; Inhibitors: SSRI antidepressants, cimetidine, diltiazem, macrolides, verapamil, nitroimidazoles, sedative hypnotics, fluoroquinolones, antihistamines);'
4. taking any medication 14 days before the trial;
5. taking any investigational drug or participating in any investigational drug within 3 months before the screening period;
6. previous history of organic heart disease, heart failure, myocardial infarction, angina pectoris, unexplained arrhythmia, torssion ventricular tachycardia, ventricular tachycardia, long QT syndrome or symptoms of long QT syndrome and family history (genetic proof or sudden death of a close relative at young age);
7. major surgery within 6 months before the screening period or surgical incision did not heal completely;
8. history of any clinically serious illness or disease or condition considered by the investigators to be likely to affect the results of the trial, including but not limited to a history of cardiac, respiratory, endocrine, nervous, digestive, urinary, or hematologic, immunologic, psychiatric, or metabolic diseases;
9. specific allergic history (asthma, measles, eczema, etc.) or allergic constitution (presence of two or more allergens), or allergic to EGFR receptor inhibitor drugs or any component of the trial drugs; allergic to any food ingredients or have special requirements for diet and cannot abide by the uniform diet;
10. smoking more than 5 cigarettes per day within 3 months before screening period and unable to quit during the trial;
11. Heavy drinking or regular drinking within 3 months before the screening period, defined as drinking more than 14 units of alcohol per week (1 unit =360ml of beer or 45 ml of 40% spirits or 150 ml of wine); Or alcohol breath test \> 0.0mg /100mLduring screening;
12. history of drugs use or drugs abuse screening positive;
13. special diet (including dragon fruit, mango, grapefruit, and/or xanthine diet, chocolate) and/or drank excessive tea, coffee, grapefruit/grapefruit juice and/or caffeinated beverages (more than 8 cups per day, 200 mL per cup on average) within 2 weeks before the first dose of research medication;
14. Pregnant or lactating women, or pregnancy screening positive;
15. Sujects plan to have a child during the trial or within 6 months after completion of the trial, or do not agree that heself /herself and his/her spouse use strict contraception (condoms, contraceptive sponges, contraceptive gels, contraceptive membranes, intrauterine devices, oral or injectable contraceptives, subcutaneous implants, or other contraceptive methods) during the trial and within 6 months after completion of the trial.
16. History of lost blood or donated a blood volume of 400 mL within 3 months before the screening period or planing to donate blood within 1 month after the end of the trial;
17. Subjects were vaccinated within 15 days before screening or planing to be vaccinated during the trial, or have not been vaccinated against COVID-19;
18. Subjects may be unable to complete the study for other reasons or may be considered inappropriate by the investigator.

Primary outcomes:
measure: Cmax
timeFrame: Blood samples will be collected from each subject after the administration of ASK120067 on Day 1 and Day 15 in arm A ,and on Day 1 and Day 11 in arm B (pre-dose, 0.25h,0.5h, 1h,1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 12h, 24h,36h,48h,72 h post dose)
measure: AUC
timeFrame: Blood samples will be collected from each subject after the administration of ASK120067 on Day 1 and Day 15 in arm A ,and on Day 1 and Day 11 in arm B (pre-dose, 0.25h,0.5h, 1h,1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 12h, 24h,36h,48h,72 h post dose)
Secondary outcomes:
measure: Tmax
timeFrame: Blood samples will be collected from each subject after the administration of ASK120067 on Day 1 and Day 15 in arm A ,and on Day 1 and Day 11 in arm B (pre-dose, 0.25h,0.5h, 1h,1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 12h, 24h,36h,48h,72 h post dose)
measure: t1/2
timeFrame: Blood samples will be collected from each subject after the administration of ASK120067 on Day 1 and Day 15 in arm A ,and on Day 1 and Day 11 in arm B (pre-dose, 0.25h,0.5h, 1h,1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 12h, 24h,36h,48h,72 h post dose)
measure: CL/F
timeFrame: Blood samples will be collected from each subject after the administration of ASK120067 on Day 1 and Day 15 in arm A ,and on Day 1 and Day 11 in arm B (pre-dose, 0.25h,0.5h, 1h,1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 12h, 24h,36h,48h,72 h post dose)
measure: Vd/F
timeFrame: Blood samples will be collected from each subject after the administration of ASK120067 on Day 1 and Day 15 in arm A ,and on Day 1 and Day 11 in arm B (pre-dose, 0.25h,0.5h, 1h,1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 12h, 24h,36h,48h,72 h post dose)
measure: λz
timeFrame: Blood samples will be collected from each subject after the administration of ASK120067 on Day 1 and Day 15 in arm A ,and on Day 1 and Day 11 in arm B (pre-dose, 0.25h,0.5h, 1h,1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 12h, 24h,36h,48h,72 h post dose)
measure: Incidence and Severity of Treatment-Emergent Adverse Events
timeFrame: Adverse events will be collected from baseline until 18 days of arm A or 14 days of arm B after the first dose administration and the follow-up period
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Drum Tower Hospital of Nanjing University School of Medical
state: Jiangsu
Study officials:
affiliation: Drum Tower Hospital of Nanjing University School of Medical
name: Juan Li
role: PRINCIPAL_INVESTIGATOR
References: