Healthy Subjects
Conditions
Brief summary
This is a single-center, open-label phase I clinical study to investigate the effect of SKLB1028 on the pharmacokinetics of Midazolam and its metabolite 1'-OH-midazolam in healthy subjects. This study also aims to evaluate the safety and tolerability of SKLB1028 in the presence of Midazolam.
Detailed description
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.
Interventions
DRUGSKLB1028
SKLB1028, capsule, oral
DRUGMidazolam
Midazolam Maleate, tablet, oral
Sponsors
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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 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; 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 with sleep apnea syndrome; 4. Subjects with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption; 5. Subjects with acute angle closure glaucoma; 6. 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; 7. 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; 8. Use of any prescription drug, over-the-counter drug, herbal medicine or health products within 2 weeks prior to screening; 9. History of drug abuse within 1 year prior to screening, or positive urine drug screen at screening; 10. Smoking more than 5 cigarettes per day within 6 months prior to screening; 11. 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; 12. 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; 13. Subjects who have received vaccinations within 4 weeks prior to screening; 14. Participation in another clinical trial within 3 months before screening (whichever is administrated); 15. 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; 16. 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; 17. 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); 18. Any positive test result of hepatitis B surface antigen or hepatitis C virus antibody, or subjects with a history of hepatitis B; 19. Any positive test result of anti-human immunodeficiency virus antibody or anti-Treponema pallidum specific antibody; 20. Subjects with a history of fainting needle or blood, cannot tolerate vein puncture for blood collection; 21. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum concentration (Cmax)of Midazolam and its metabolite 1'-OH-midazolam | Day 1 and Day 3(0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hrs post-dose) |
| Area under the concentration-time curve (AUC) from 0 to the last measurable concentration (AUC0-t) of Midazolam and its metabolite 1'-OH-midazolam | Day 1 and Day 3(0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hrs post-dose) |
| AUC extrapolated to infinity (AUCinf) of Midazolam and its metabolite 1'-OH-midazolam | Day 1 and Day 3(0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hrs post-dose) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Cmax (Tmax) of Midazolam and its metabolite 1'-OH-midazolam | Day 1 and Day 3(0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hrs post-dose) | — |
| Terminal elimination half-life (t1/2) of Midazolam and its metabolite 1'-OH-midazolam | Day 1 and Day 3(0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hrs post-dose) | — |
| Apparent Clearance (CLz/F) of Midazolam | Day 1 and Day 3(0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hrs post-dose) | — |
| Apparent volume of distribution (Vz/F) of Midazolam | Day 1 and Day 3(0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hrs post-dose) | — |
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | Throughout the study period, with an average of 10 days | — |
| Clinically significant changes from baseline in routine blood test were recorded as AEs at each visit time point. | Throughout the study period, with an average of 10 days | Routine blood test included cell count (white blood cells, platelets, basophils, eosinophils, neutrophils, lymphocytes and monocytes) in 10\^9/L. |
| Clinically significant changes from baseline in blood biochemistry test were recorded as AEs at each visit time point. | Throughout the study period, with an average of 10 days | Blood biochemistry test included total bilirubin and serum creatinine in μmol/L. |
| Clinically significant changes from baseline in routine urine test were recorded as AEs at each visit time point. | Throughout the study period, with an average of 10 days | Routine urine test included urobilinogen, protein, glucose and ketones (positive or negative). |
| Clinically significant changes from baseline in coagulation function test were recorded as AEs at each visit time point. | Throughout the study period, with an average of 10 days | Coagulation function test included prothrombin time and activated partial thromboplastin time in seconds. |
| Clinically significant changes from baseline in 12-lead electrocardiogram (ECG) examination were recorded as AEs at each visit time point. | Throughout the study period, with an average of 10 days | ECG monitoring included heart rate in bpm. |
| Clinically significant changes from baseline in vital signs examination were recorded as AEs at each visit time point. | Throughout the study period, with an average of 10 days | Vital signs monitoring included body temperature in degrees Celsius. |
| Clinically significant changes from baseline in physical examination were recorded as AEs at each visit time point. | Throughout the study period, with an average of 10 days | Physical examination included general conditions, skin, mucous membranes, head, neck, chest, abdomen, spine, limbs, nervous system, and lymphatic system. |
Countries
China
Outcome results
None listed