A Study to Evaluate the Pharmacokinetics of HSK21542 in Subjects With Renal Impairment

An Open-label, Single-dose Study to Assess the Pharmacokinetics of HSK21542 Injection in Subjects With Varying Degrees of Renal Impairment Compared to the Control Subjects With Normal Renal Function

This is an open-label, single-dose study to evaluate the pharmacokinetics and safety of HSK21542 in subjects with mild, moderate and severe renal impairment compared to the matched control subjects with normal renal function.

Study Overview

• Status: Recruiting
• Conditions: Renal Impairment
• Intervention / Treatment: Drug: HSK21542 Injection

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Meixia Chen, PhD; Phone Number: 028-67258779; Email: chenmeixia@haisco.com

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250014
      • Recruiting
      • Shandong Provincial Qianfoshan Hospital
      • Contact: Wei Zhao, PhD; Phone Number: 0531-89268212

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Subjects with renal impairment(RI):

1. Voluntarily sign the informed consent form, understand the trial procedures, and be willing to comply with all trial procedures and restrictions;
2. 18 years to 79 years (inclusive), male and female;
3. Male subjects weight ≥50 kg and female subjects weight ≥45 kg. Body mass index (BMI) : 18-30 kg/m2 (inclusive) (BMI= weight (kg)/height2 (m^2));
4. Subjects with medically stable RI until study completion corresponding to the classifications of Renal Function based on GFR: mild RI: 60≤GFR<90 mL/min; moderate RI: 30≤GFR<60 mL/min, severe RI:15≤GFR<30 mL/min;
5. Physical examination, vital sign measurements, 12-lead electrocardiogram (ECG), and clinical laboratory tests results were deemed appropriate by the investigator;
6. Not in use of any drug within 2 weeks prior to screening, except for the medication necessary for RI/ other comorbidities (last more than four weeks in good compliance);
7. Subjects (including partners) are willing to voluntarily use effective contraceptives from screening to at least 6 months after the last dose administration.

Subjects with normal renal function :

1. Voluntarily sign the informed consent form, understand the trial procedures, and be willing to comply with all trial procedures and restrictions;
2. 18 years to 79 years (inclusive), male and female, age and sex must be matched with subjects with RI;
3. Male subjects weight ≥50 kg and female subjects weight ≥45 kg, weight must be matched with subjects with RI. Body mass index (BMI) : 18-30 kg/m^2 (inclusive) (BMI= weight (kg)/height2 (m^2));
4. 90≤GFR<130 mL/min;
5. Physical examination, vital sign measurements, 12-lead electrocardiogram (ECG), and clinical laboratory tests results were deemed appropriate by the investigator;
6. Not in use of any drug within 2 weeks prior to screening, except for the medication necessary for comorbidities (last more than four weeks in good compliance);
7. Subjects (including partners) are willing to voluntarily use effective contraceptives from screening to at least 6 months after the last dose administration.

Exclusion Criteria:

1. Subjects who have a allergic to any component of HSK21542 injection or allergic history to opiates, such as urticaria (opiate-related adverse reactions such as constipation and nausea are not included as exclusion criteria in this study);
2. Have a history of severe and uncontrolled diseases, such as cardiovascular, respiratory, liver, gastrointestinal, endocrine, hematologic, mental/nervous systems diseases within one year prior to screening;
3. Have conditions that may affect drug absorption, distribution, metabolism, or excretion (e.g., disease, drugs or surgery);
4. Acute renal failure;
5. Smoking more than 5 cigarettes per day within 3 months prior to screening or smoking during the study;
6. Average alcohol intake is more than 14 unit per week (1unit=17.7 mL alcohol , 1 unit=357mL 5% alcohol beer, or 43mL 40% alcohol spirit, or 147mL 12% alcohol wine) within the 3 months prior to screening, or taking any alcohol during study or a positive ethanol breath test at screening;
7. Drug abuse history within 5 years prior to screening, or positive urine drug screen at screening;
8. History of high consumption of grapefruit juice, methylxanthine-rich food or beverage (such as coffee, tea, cola, chocolate, energy drinks) ,consumption of grapefruit juice, methylxanthine-rich food within 48 hours before the administration;
9. Participation in another clinical trial within 3 months before screening;
10. Blood donation (or blood loss) ≥400 mL, or receiving blood products to improve anemia within 3 months prior to the screening;
11. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) > 2 × upper limit of normal, or bilirubin > 1.5 × upper limit of normal;
12. Have a positive result for hepatitis B surface antigen, hepatitis C virus antibody, human immunodeficiency virus antibody, or anti-treponema pallidum specific antibody;
13. A pregnant/lactating woman, or has a positive pregnancy test at screening or during the trial;
14. Not suitable for this study as judged by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mild Renal Impairment	Drug: HSK21542 Injection; 1ug/kg bolus for 2min±5s
Experimental: Moderate Renal Impairment	Drug: HSK21542 Injection; 1ug/kg bolus for 2min±5s
Experimental: Severe Renal Impairment	Drug: HSK21542 Injection; 1ug/kg bolus for 2min±5s
Experimental: Normal Renal function	Drug: HSK21542 Injection; 1ug/kg bolus for 2min±5s

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	The maximun plasma concentration of HSK21542	From the start to 240 hours after bolus
AUC0-t	Area under the concentration-time curve from time zero to time of last quantifiable concentration	From the start to 240 hours after bolus
AUC0-inf	Area under the concentration-time curve from time zero extrapolated to infinite time	From the start to 240 hours after bolus

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tmax	Time of maximum concentration	From the start to 240 hours after bolus
t1/2	half-life	From the start to 240 hours after bolus
Vz	Volume of distribution associated with the terminal phase	From the start to 240 hours after bolus
CL	Plasma clearance	From the start to 240 hours after bolus
Ae	Cumulative urinary recovery of unchanged drug	Predose and 72 hours after dosing
Fe	Cumulative urinary recovery fraction of unchanged drug	Predose and 72 hours after dosing
CLr	Renal clearance	Predose and 72 hours after dosing

Collaborators and Investigators

• Sponsor: Haisco Pharmaceutical Group Co., Ltd.
• Investigators: Principal Investigator: Wei Zhao, PhD, Qianfoshan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2023
• Primary Completion (Estimated): July 30, 2023
• Study Completion (Estimated): December 30, 2023

Study Registration Dates

• First Submitted: June 29, 2023
• First Submitted That Met QC Criteria: July 12, 2023
• First Posted (Actual): July 17, 2023

Study Record Updates

• Last Update Posted (Actual): July 17, 2023
• Last Update Submitted That Met QC Criteria: July 12, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency
• Other Study ID Numbers: HSK21542-104

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No