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

NCT05070195 | Completed Phase 1

• 1 other identifier: HA114-CSP-011
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (23)

• 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

Study Arms (1)

The DDI of SKLB1028 and Midazolam

EXPERIMENTAL

Eligible subjects received a single dose of Midazolam 15 mg on Day 1, and took a single dose of Midazolam 15 mg and a single dose of SKLB1028 150 mg with dosing interval of 0.5 h on Day 3.

Drug: SKLB1028; Drug: Midazolam

Interventions

SKLB1028 DRUG

SKLB1028, capsule, oral

The DDI of SKLB1028 and Midazolam

Midazolam DRUG

Midazolam Maleate, tablet, oral

The DDI of SKLB1028 and Midazolam

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy subjects:
• Voluntarily sign the informed consent form, understand the trial procedures, and be willing to comply with all trial procedures and restrictions;
• ≤ 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• CSPC ZhongQi Pharmaceutical Technology Co., Ltd.: lead

Study Sites (1)

Beijing Friendship Hospital, Capital Medical University

Beijing, China

Location

MeSH Terms

Interventions

SKLB1028; Midazolam

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2021
• First Posted: October 7, 2021
• Study Start: June 7, 2021
• Primary Completion: July 9, 2021
• Study Completion: July 9, 2021
• Last Updated: October 7, 2021

Record last verified: 2021-09

Locations

CN (1)