Drug-drug Interaction Study Beteewn ASK120067 and Rifampicin or Itraconazole

NCT ID: NCT05631678

Last Updated: 2022-11-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-06
• Study Completion Date: 2022-08-03

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.

Conditions

Locally Advanced or Metastatic NSCLC

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

the effect of oral rifampicin on the pharmacokinetics of ASK120067 tablets

Take ASK120067 tablets orally once on the first day at 160mg in fast condition；Take rifampicin capsules orally once on the days 8 to 17 at 600mg in fast condition, and a combination of 160mg ASK120067 and 600mg rifampicin were administrated on the 15th day in fast condition.

Group Type: EXPERIMENTAL

Rifampicin; ASK120067

Intervention Type: DRUG

Take ASK120067 tablets orally once on the first day at 160mg in fast condition;Take rifampicin capsules orally once on the days 8 to 17 at 600mg in fast condition, and a combination of 160mg ASk120067 and 600mg rifampicin were administrated on the 15th day in fast condition.

effect of oral itraconazole on the pharmacokinetics of ASK120067 tablets

Take ASK120067 tablets orally once on the first day at 80mg in fast condition；Take itraconazole capsules orally twice on the days 8 to 13 at 200mg in fed condition, and a combination of 80mg ASK120067 and 200mg itraconazole were administrated on the 11th day in fast condition.

Group Type: EXPERIMENTAL

ASK120067;itraconazole

Intervention Type: DRUG

Take ASK120067 tablets orally once on the first day at 80mg in fast condition;Take itraconazole capsules orally twice on the days 8 to 13 at 200mg in fed condition, and a combination of 80mg ASK120067 and 200mg itraconazole were administrated on the 11th day in fast condition.

Interventions

Rifampicin; ASK120067

Take ASK120067 tablets orally once on the first day at 160mg in fast condition;Take rifampicin capsules orally once on the days 8 to 17 at 600mg in fast condition, and a combination of 160mg ASk120067 and 600mg rifampicin were administrated on the 15th day in fast condition.

Intervention Type: DRUG

ASK120067;itraconazole

Take ASK120067 tablets orally once on the first day at 80mg in fast condition;Take itraconazole capsules orally twice on the days 8 to 13 at 200mg in fed condition, and a combination of 80mg ASK120067 and 200mg itraconazole were administrated on the 11th day in fast condition.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Jiangsu Aosaikang Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Juan Li

Role: PRINCIPAL_INVESTIGATOR

Drum Tower Hospital of Nanjing University School of Medical

Locations

Drum Tower Hospital of Nanjing University School of Medical

Nanjing, Jiangsu, China

Countries

China

References

Cao B, Huang L, Liu M, Lin H, Ma T, Zhao Y, Geng Y, Yang Y, Guo H, Li J. Phase 1 study to evaluate the effects of rifampin or itraconazole on the pharmacokinetics of limertinib (ASK120067), a novel mutant-selective inhibitor of the epidermal growth factor receptor in healthy Chinese subjects. Expert Opin Drug Metab Toxicol. 2023 Sep;19(9):653-664. doi: 10.1080/17425255.2023.2260738. Epub 2023 Oct 12.

Reference Type: DERIVED

PMID: 37811634 (View on PubMed)

Other Identifiers

ASK120067-PK-1

Identifier Type: -

Identifier Source: org_study_id