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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Renal Impairment

Intervention / Treatment
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* Drug: HSK21542 Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with renal impairment(RI): Voluntarily sign the informed consent form, understand the trial procedures, and be willing to comply with all trial procedures and restrictions; 18 years to 79 years (inclusive), male and female; 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)); 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; Physical examination, vital sign measurements, 12-lead electrocardiogram (ECG), and clinical laboratory tests results were deemed appropriate by the investigator; 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); 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 : Voluntarily sign the informed consent form, understand the trial procedures, and be willing to comply with all trial procedures and restrictions; 18 years to 79 years (inclusive), male and female, age and sex must be matched with subjects with RI; 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)); 90≤GFR<130 mL/min; Physical examination, vital sign measurements, 12-lead electrocardiogram (ECG), and clinical laboratory tests results were deemed appropriate by the investigator; 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); Subjects (including partners) are willing to voluntarily use effective contraceptives from screening to at least 6 months after the last dose administration. Exclusion Criteria: 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); 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; Have conditions that may affect drug absorption, distribution, metabolism, or excretion (e.g., disease, drugs or surgery); Acute renal failure; Smoking more than 5 cigarettes per day within 3 months prior to screening or smoking during the study; 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; Drug abuse history within 5 years prior to screening, or positive urine drug screen at screening; 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; Participation in another clinical trial within 3 months before screening; Blood donation (or blood loss) ≥400 mL, or receiving blood products to improve anemia within 3 months prior to the screening; Aspartate aminotransferase (AST), alanine aminotransferase (ALT) > 2 × upper limit of normal, or bilirubin > 1.5 × upper limit of normal; Have a positive result for hepatitis B surface antigen, hepatitis C virus antibody, human immunodeficiency virus antibody, or anti-treponema pallidum specific antibody; A pregnant/lactating woman, or has a positive pregnancy test at screening or during the trial; Not suitable for this study as judged by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |