A Study to Investigate the Drug-drug Interactions (DDIs) Between SKLB1028 and Midazolam in Healthy Subjects

This study aims to characterize the drug-drug Interactions (DDI) potential of SKLB1028 with the sensitive index substrate drug (Midazolam) in Healthy Subjects. The 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.

Inclusion criteria

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Healthy subjects:

• Voluntarily sign the informed consent form, understand the trial procedures, and be willing to comply with all trial procedures and restrictions;
• 18 ≤ age ≤45, male;
• Subjects with weight ≥50.0 kg and body mass index (BMI) 19-26 kg/m^2 (inclusive);
• Subjects are willing to use effective non-hormonal contraceptives such as sexual abstinence, 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;
• Ability to communicate well with researchers, and be willing to comply with all trial requirements.

Exclusion criteria

• Allergic constitution, including a history of allergy to any of the study drugs or other similarly structured drugs;
• 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;
• Subjects with sleep apnea syndrome;
• Subjects with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption;
• Subjects with acute angle closure glaucoma;
• 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;
• Use of any inhibitors or inducers of CYP3A4, or any strong inhibitors or inducers of CYP2C8 or P-gp within 2 weeks prior to screening;
• Use of any prescription drug, over-the-counter drug, herbal medicine or health products within 2 weeks prior to screening;
• History of drug abuse within 1 year prior to screening, or positive urine drug screen at screening;
• Smoking more than 5 cigarettes per day within 6 months prior to screening;
• 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;
• 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;
• Subjects who have received vaccinations within 4 weeks prior to screening;
• Participation in another clinical trial within 3 months before screening (whichever is administrated);
• 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;
• 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;
• 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);
• Any positive test result of hepatitis B surface antigen or hepatitis C virus antibody, or subjects with a history of hepatitis B;
• Any positive test result of anti-human immunodeficiency virus antibody or anti-Treponema pallidum specific antibody;
• Subjects with a history of fainting needle or blood, cannot tolerate vein puncture for blood collection;
• Any condition that, in the opinion of the Investigator, may prevent the subject from completing the study or pose a significant risk to the subject.