Metabolism and Excretory of HSK21542 in Maintenance Hemodialysis Patients

A Phase I Clinical Trial Exploring the Metabolic and Excretion Characteristics of HSK21542 Injection in Maintenance Hemodialysis Patients

This is a single-center, nonrandomized, and open design study to investigate metabolism and excretion of HSK21542 in maintenance hemodialysis patients.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease Patients
• Intervention / Treatment: Drug: HSK21542 Injection

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China
      • The First Affiliated Hospital of Shandong First Medical University (Shandong Provincial Qianfoshan Hospital)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subjects who are willing to sign an informed consent form, fully understand the objectives and purposes of the study, and are willing to comply with the study protocol before any of the study-related procedures start.
2. Age ≥18 years old, Male or female;
3. Patients with end-stage renal diseases who receive hemodialysis (including hemodiafiltration) 3 times in a week prior to screening for at least 3 months;
4. Dry weight is 40.0-135.0 kg (inclusive) during the screening period;
5. Patients with at least two occurrences of single-compartment urea clearance (sp Kt/V) ≥ 1.2, or at least two occurrences of urea reduction ratio (URR) ≥ 65%, or one occurrence of sp Kt/V ≥ 1.2 and one occurrence of URR ≥ 65% on different days of dialysis within 6 months before administration;
6. Female of childbearing age or Male must agree to adopt efficient contraceptive measures in sexual intercourse during the study period and within 3 months after the last administration; Menopausal female subjects should have had menopause at least one year or should have had permanent sterilization (e.g., fallopian tube occlusion, hysterectomy, bilateral salpingectomy).

Exclusion Criteria:

1. Expected to undergo kidney transplantation and/or parathyroidectomy during the study;
2. History of allergy to opioids, such as urticaria (Note: adverse effects related to opioid use, such as constipation and nausea, are not included as the exclusion criteria in this study);
3. Used opioids within 7 days before screening, or unable to avoid the use of opioids other than the investigational product during the study;
4. Participated in any clinical trial of other drug or medical device within 1 month before screening (received study medication or treated by the medical device in the clinical trial);
5. Used blood perfusion during the screening period or expected study period;
6. Blood pressure of upper limbs in the supine position at screening: systolic blood pressure < 90 mmHg, or diastolic blood pressure < 60 mmHg, or systolic blood pressure > 180 mmHg, or diastolic blood pressure > 110 mmHg;
7. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST)≥ 2.5 × upper limit of normal (ULN), or total bilirubin ≥ 2 × upper limit of normal (ULN) at screening;
8. Blood sodium > 155 mmol/L at screening;
9. Blood donation (or loss) ≥ 400 mL within the first 3 months of screening or Hemoglobin < 80 g/L at screening;
10. Positive for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCVAb), syphilis antibody, or human immunodeficiency virus (HIV) antibody;
11. Females who are pregnant or breastfeeding;
12. Smoking an average of more than 5 cigarettes per day within the first 3 months of screening, or not stopping the use of any tobacco products during the trial period;

13. Any physiological or psychological diseases or conditions that may increase the risk of the trial, affect the subject's compliance with the protocol, or affect the subject's completion of the trial, as judged by the study physician, including but not limited to:

    1. Known or suspected alcohol, anesthetic, or other substance abuse or drug dependence history within the first 12 months of screening; Baseline urine drug screening (if any) or positive alcohol breath test;
    2. severe systolic or diastolic heart failure within the first 6 months of screening (e.g. NYHA grade IV congestive heart failure (NYHA heart function grading criteria can be found in Appendix 3) ;
    3. Severe mental illness or cognitive impairment (e.g., dementia);
    4. Any other relevant acute or chronic neurological and psychiatric diseases (e.g., encephalopathy, coma, delirium) within 3 months before screening And the researchers believe it is not suitable for enrollment;
    5. Patients with malignant tumors, but not including: curable cervical carcinoma in situ, skin basal cell carcinoma, or squamous cell carcinoma, or any other tumor that has been cured (with no evidence of disease recurrence within 5 years).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.8 μg/kg HSK21542 Injection	Drug: HSK21542 Injection; A single intravenous dose of 0.8 μg/kg HSK21542 in boluses after D1 dialysis completed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative recovery of unchanged drug (Ae)	The pharmacokinetic parameters of HSK21542 in urine, feces, and dialysate	From the start of administration to 168 hours after administration
Cumulative recovery fraction of unchanged drug (Fe)	The pharmacokinetic parameters of HSK21542 in urine, feces, and dialysate	From the start of administration to 168 hours after administration
Plasma clearance	The pharmacokinetic parameters of HSK21542 in urine, feces, and dialysate	From the start of administration to 168 hours after administration
Cmax	The pharmacokinetic parameters of HSK21542 in plasma	From the start of administration to 168 hours after administration
AUC(0-t)	The pharmacokinetic parameters of HSK21542 in plasma	From the start of administration to 168 hours after administration
AUC(0-∞)	The pharmacokinetic parameters of HSK21542 in plasma	From the start of administration to 168 hours after administration
Tmax	The pharmacokinetic parameters of HSK21542 in plasma	From the start of administration to 168 hours after administration
t1/2	The pharmacokinetic parameters of HSK21542 in plasma	From the start of administration to 168 hours after administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The main metabolites of HSK21542	The main metabolites of HSK21542 in plasma, urine, feces, and dialysate	From the start of administration to 168 hours after administration
Adverse events (AEs)	The incidence and severity of AEs	From after administration to the end of telephone follow-up

Collaborators and Investigators

• Sponsor: Haisco Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2023
• Primary Completion (Actual): November 21, 2023
• Study Completion (Actual): February 27, 2024

Study Registration Dates

• First Submitted: January 21, 2024
• First Submitted That Met QC Criteria: February 1, 2024
• First Posted (Actual): February 2, 2024

Study Record Updates

• Last Update Posted (Actual): August 20, 2024
• Last Update Submitted That Met QC Criteria: August 19, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: HSK21542-105

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