A Study to Investigate the Drug-drug Interactions (DDIs) of SKLB1028 With Itraconazole, Gemfibrozil or Rifampicin in Healthy Subjects

CSPC Pharmaceutical Group

Status and phase: Unknown; Phase 1

Conditions: Healthy Subjects

Treatments: Drug: Gemfibrozil; Drug: Itraconazole; Drug: SKLB1028; Drug: Rifampicin

Study type: Interventional

Funder types: Industry

Identifiers

NCT05069870

HA114-CSP-009

Details and patient eligibility

About

This is a three-part, single-center, open-label phase I clinical study to characterize the DDIs potential of SKLB1028 with Itraconazole, Gemfibrozil or Rifampicin in healthy subjects. This study also aims to evaluate the safety and tolerability of SKLB1028 in the presence of Itraconazole, Gemfibrozil or Rifampicin.

Full description

SKLB1028 is the potential substrate of CYP3A4, CYP2C8 and P-gp. This study conducted in three parts to characterize the DDIs potential of SKLB1028 with the perpetrator drugs ( Itraconazole, Gemfibrozil, Rifampicin) in Healthy Subjects. Each part of this study consists of a screening period (Day -14 to Day -2), a baseline period (Day -1), a treatment period, and a follow-up visit period.

Enrollment: 42 patients

Sex: Male

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

Healthy subjects:

1. Voluntarily sign the informed consent form, understand the trial procedures, and be willing to comply with all trial procedures and restrictions;
2. 18 ≤ age ≤45, male;
3. Subjects with weight ≥50.0 kg and body mass index (BMI) 19-26 kg/m^2 (inclusive);
4. Subjects are willing to use effective contraceptives and not allowed to donate sperm from screening to the 6 months after the last dose administration unless permanent contraception has been taken, such as vasectomy.
5. Ability to communicate well with researchers, and be willing to comply with all trial requirements.

Exclusion criteria

1. Allergic constitution, including a history of allergy to any of the study drugs or other similarly structured drugs;
2. Previous or current severe diseases, such as cardiovascular, respiratory, gastrointestinal, endocrine, hematological, psychiatric/neurological systems diseases, or any other disease that can interfere with the results of the study;
3. Subjects who have previously undergone surgery that may affect the absorption, distribution, metabolism, or excretion of the drug (e.g., subtotal gastrectomy), or who have a scheduled surgical plan during the study period;
4. Use of any strong inhibitors or inducers of CYP3A4, CYP2C8 or P-gp within 2 weeks prior to screening;
5. Use of any prescription drug, over-the-counter drug, herbal medicine or health products within 2 weeks prior to screening;
6. History of drug abuse within 1 year prior to screening, or positive urine drug screen at screening;
7. Smoking more than 5 cigarettes per day within 6 months prior to screening;
8. Average daily intake of alcohol more than 14 units (14 units ≈285 mL of beer, or 25 mL of liquor, or 150 mL of wine) within 4 weeks prior to screening, or a positive ethanol breath test at screening;
9. Consumption of grapefruit juice, methylxanthine-rich food or beverage (such as coffee, tea, cola, chocolate, energy drinks) within 48 h before the administration, or those who have had strenuous exercise, or have other factors affecting absorption, distribution, metabolism, excretion, etc of the drug;
10. Participation in another clinical trial within 3 months before screening (whichever is administrated);
11. Blood donation (or blood loss) ≥200 mL within 4 weeks prior to the screening, or who have a blood donation plan during the entire study or within 1 months after the study;
12. Any abnormalities of clinical significance in physical examination, vital signs, clinical laboratory tests (routine blood test, blood biochemistry, routine urine test, coagulation function), anteroposterior chest radiograph or chest CT scan;
13. Abnormalities of clinical significance in 12-lead ECG examination (such as tachycardia/bradycardia in need of medical treatment, II-III degree atrioventricular block, QTcF>450 ms or any other clinically significant abnormalities );
14. Any positive test result of hepatitis B surface antigen or hepatitis C virus antibody, or subjects with a history of hepatitis B;
15. Any positive test result of anti-human immunodeficiency virus antibody or anti-Treponema pallidum specific antibody;
16. Any condition that, in the opinion of the Investigator, may prevent the subject from completing the study or poses a significant risk to the subject.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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42 participants in 3 patient groups

The DDI of SKLB1028 and Itraconazole

Experimental group

Description:

Eligible subjects received a single dose of SKLB1028 100 mg on Day 1, then took Itraconazole 200 mg twice-daily on Day 8 and 200 mg once-daily on Day 9 through Day 18, and took a single dose of SKLB1028 100 mg on Day 11.

Treatment:

Drug: SKLB1028

Drug: Itraconazole

The DDI of SKLB1028 and Gemfibrozil

Experimental group

Description:

Eligible subjects received a single dose of SKLB1028 100 mg on Day 1, then took Gemfibrozil 600 mg twice-daily on Day 8 through Day 19, and took a single dose of SKLB1028 100 mg on Day 12.

Treatment:

Drug: Gemfibrozil

Drug: SKLB1028

The DDI of SKLB1028 and Rifampicin

Experimental group

Description:

Eligible subjects received a single dose of SKLB1028 150 mg on Day 1, then took Rifampicin 600 mg once-daily on Day 8 through Day22, and took a single dose of SKLB1028 150 mg on Day 15.

Treatment:

Drug: Rifampicin

Drug: SKLB1028