Clinical trial NCT05947097: A Study to Evaluate the Pharmacokinetics of HSK21542 in Subjects With Renal Impairment
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Renal Impairment
Lead sponsor: Haisco Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-07-17
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Cmax
timeFrame: From the start to 240 hours after bolus
measure: AUC0-t
timeFrame: From the start to 240 hours after bolus
measure: AUC0-inf
timeFrame: From the start to 240 hours after bolus
Secondary outcomes:
measure: Tmax
timeFrame: From the start to 240 hours after bolus
measure: t1/2
timeFrame: From the start to 240 hours after bolus
measure: Vz
timeFrame: From the start to 240 hours after bolus
measure: CL
timeFrame: From the start to 240 hours after bolus
measure: Ae
timeFrame: Predose and 72 hours after dosing
measure: Fe
timeFrame: Predose and 72 hours after dosing
measure: CLr
timeFrame: Predose and 72 hours after dosing
Other outcomes:
Locations:
city: Jinan
country: China
facility: Shandong Provincial Qianfoshan Hospital
state: Shandong
Study officials:
affiliation: Qianfoshan Hospital
name: Wei Zhao, PhD
role: PRINCIPAL_INVESTIGATOR
References: