Clinical trial NCT05070195: A Study to Investigate the Drug-drug Interactions (DDIs) Between SKLB1028 and Midazolam in Healthy Subjects
Official title: A Single-center, Open-label, Phase I Drug-drug Interaction Clinical Study to Investigate the Effect of SKLB1028 on the Pharmacokinetics of Midazolam in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Lead sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-10-07
Enrollment: 14
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

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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.

Primary outcomes:
measure: Maximum concentration (Cmax)of Midazolam and its metabolite 1'-OH-midazolam
timeFrame: Day 1 and Day 3(0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hrs post-dose)
measure: Area under the concentration-time curve (AUC) from 0 to the last measurable concentration (AUC0-t) of Midazolam and its metabolite 1'-OH-midazolam
timeFrame: Day 1 and Day 3(0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hrs post-dose)
measure: AUC extrapolated to infinity (AUCinf) of Midazolam and its metabolite 1'-OH-midazolam
timeFrame: 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 outcomes:
measure: Time to Cmax (Tmax) of Midazolam and its metabolite 1'-OH-midazolam
timeFrame: Day 1 and Day 3(0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hrs post-dose)
measure: Terminal elimination half-life (t1/2) of Midazolam and its metabolite 1'-OH-midazolam
timeFrame: Day 1 and Day 3(0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hrs post-dose)
measure: Apparent Clearance (CLz/F) of Midazolam
timeFrame: Day 1 and Day 3(0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hrs post-dose)
measure: Apparent volume of distribution (Vz/F) of Midazolam
timeFrame: Day 1 and Day 3(0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hrs post-dose)
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
timeFrame: Throughout the study period, with an average of 10 days
measure: Clinically significant changes from baseline in routine blood test were recorded as AEs at each visit time point.
timeFrame: Throughout the study period, with an average of 10 days
measure: Clinically significant changes from baseline in routine blood test were recorded as AEs at each visit time point.
timeFrame: Throughout the study period, with an average of 10 days
measure: Clinically significant changes from baseline in routine blood test were recorded as AEs at each visit time point.
timeFrame: Throughout the study period, with an average of 10 days
measure: Clinically significant changes from baseline in blood biochemistry test were recorded as AEs at each visit time point.
timeFrame: Throughout the study period, with an average of 10 days
measure: Clinically significant changes from baseline in blood biochemistry test were recorded as AEs at each visit time point.
timeFrame: Throughout the study period, with an average of 10 days
measure: Clinically significant changes from baseline in blood biochemistry test were recorded as AEs at each visit time point.
timeFrame: Throughout the study period, with an average of 10 days
measure: Clinically significant changes from baseline in blood biochemistry test were recorded as AEs at each visit time point.
timeFrame: Throughout the study period, with an average of 10 days
measure: Clinically significant changes from baseline in routine urine test were recorded as AEs at each visit time point.
timeFrame: Throughout the study period, with an average of 10 days
measure: Clinically significant changes from baseline in routine urine test were recorded as AEs at each visit time point.
timeFrame: Throughout the study period, with an average of 10 days
measure: Clinically significant changes from baseline in coagulation function test were recorded as AEs at each visit time point.
timeFrame: Throughout the study period, with an average of 10 days
measure: Clinically significant changes from baseline in coagulation function test were recorded as AEs at each visit time point.
timeFrame: Throughout the study period, with an average of 10 days
measure: Clinically significant changes from baseline in coagulation function test were recorded as AEs at each visit time point.
timeFrame: Throughout the study period, with an average of 10 days
measure: Clinically significant changes from baseline in 12-lead electrocardiogram (ECG) examination were recorded as AEs at each visit time point.
timeFrame: Throughout the study period, with an average of 10 days
measure: Clinically significant changes from baseline in 12-lead electrocardiogram (ECG) examination were recorded as AEs at each visit time point.
timeFrame: Throughout the study period, with an average of 10 days
measure: Clinically significant changes from baseline in vital signs examination were recorded as AEs at each visit time point.
timeFrame: Throughout the study period, with an average of 10 days
measure: Clinically significant changes from baseline in vital signs examination were recorded as AEs at each visit time point.
timeFrame: Throughout the study period, with an average of 10 days
measure: Clinically significant changes from baseline in vital signs examination were recorded as AEs at each visit time point.
timeFrame: Throughout the study period, with an average of 10 days
measure: Clinically significant changes from baseline in physical examination were recorded as AEs at each visit time point.
timeFrame: Throughout the study period, with an average of 10 days
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
Study officials:
References: