A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of HSK21542 Injection in Subjects Undergoing Hemodialysis

Haisco Pharmaceutical Group Co., Ltd.131 enrolled

Overview

This is a multi-center, randomized, double-blind, placebo-controlled phase II clinical trial. The main objective is to evaluate the safety, pharmacokinetics, and efficacy of HSK21542 injection in subjects undergoing hemodialysis

This study is a multicenter study, which is divided into two stages. The first stage is a dose escalation, randomized, double-blind, placebo-controlled study of multiple intravenous administration within one week in hemodialysis subjects. The second stage is a randomized, double-blind, placebo-controlled study of Administration for 12 weeks in hemodialysis subjects with moderate or severe pruritus. In the second stage, consist of a Screening Visit, a 7-day Run-in Period, a 12 week Double-blind Treatment Period, and a 2-week Discontinuation Period. Informed consent will be obtained prior to performing any study-specific procedures. The Screening Visit will occur within 8 to 28 days prior to randomization to assess eligibility.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

131

Conditions

Uremic Pruritus

Interventions

Stage I:HSK21542 0.05 μg/kgDRUG

Following the principle of dose escalation and starting from the low dose of 0.05 μg/kg to the high dose 0.80 μg/kg

Stage I:HSK21542 0.15 μg/kgDRUG

Following the principle of dose escalation and starting from the low dose of 0.05 μg/kg to the high dose 0.80 μg/kg

Stage I:HSK21542 0.30 μg/kgDRUG

Following the principle of dose escalation and starting from the low dose of 0.05 μg/kg to the high dose 0.80 μg/kg

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Stage1: 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. Aged ≥ 18 and ≤ 75 years old, male or female; 3. Dry weight ≥ 50.0 kg at screening, body mass index (BMI = weight (kg) / height2 \[m2\]) in the range of 16.0-30.0 kg/m\^2 (inclusive); 4. Patients with end-stage renal diseases who receive hemodialysis (including hemodiafiltration) 3 times in a week prior to screening for at least 3 months; 5. Patients with at least two occurrences of single-compartment urea clearance (sp Kt/V, see Appendix 7 for the calculation formula) ≥ 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 3 months before screening; 6. Male subjects must agree to use condoms in sexual intercourse during the study and within 3 months after the last dose; female subjects should have had menopause for at least one year, or should have had permanent sterilization (e.g., fallopian tube occlusion, hysterectomy, bilateral salpingectomy); or women of childbearing potential must agree to take effective contraceptive measures during the study and within 3 months after the last dose, such as oral contraceptives, condoms, and contraceptive films. Stage1: 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 one week 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 within 3 months before screening; 6. History of medication or drug abuse; 7. Average daily alcohol consumption greater than 15 g (15 g of alcohol is equivalent to 450 mL of beer or 150 mL of wine or 50 mL of light liquor) within 3 months before screening; 8. Unable to comply with the standard dietary plan and unable to avoid coffee or tea during the study; 9. 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; 10. New York Heart Association (NYHA) Class ≥ III at screening; or confirmed to have abnormal ECG at screening and determined by the investigator to be inappropriate to be enrolled, including QTcF ≥ 480 ms; 11. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or total bilirubin ≥ 1.5 × upper limit of normal (ULN) at screening; 12. Blood sodium \> 155 mmol/L at screening; 13. Hemoglobin ≤ 80 g/L at screening; 14. Positive for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCVAb), syphilis antibody, or human immunodeficiency virus (HIV) antibody at screening; 15. Underwent major surgery (determined by the investigator as major surgery) within 3 months before screening; 16. Having a total blood loss of ≥ 200mL within 1 month before screening, except for the blood loss during menstruation in females; 17. Females who are pregnant or breastfeeding; 18. 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. Severe mental illness or cognitive impairment (e.g., dementia); 2. Any other relevant acute or chronic neurological and psychiatric diseases (e.g., encephalopathy, coma, delirium) within 3 months before screening; 3. Patients with malignant tumors (including malignant tumors that have been cured without recurrence).

Locations (1)

Guizhou Medical University Affiliated Hospital

Guiyang, Guizhou, China

Outcomes

Primary Outcomes

Stage I：Safety of HSK21542 injection for multiple times within one week in hemodialysis subjects

Adverse events (AEs) and serious adverse events (SAEs)，Vital signs、Physical examination, Laboratory examination, ECG

Time frame: From screening up to D14

Stage II：At week 12, the change in weekly average of daily Worst Itch NRS (WI-NRS) from baseline in subjects undergoing hemodialysis

Change from baseline in average NRS score of itch at week 12

Time frame: 12 week

Secondary Outcomes

Stage I：Area under the plasma concentration versus time curve (AUC)

Plasma HSK21542 Area Under the Concentration-time Curve (AUC)

Time frame: 1 week

Stage I：Time to the peak plasma concentration (Tmax)

Time to Maximum Plasma HSK21542 Concentration

Time frame: 1 week

Stage I：Maximum Concentration (Cmax)

Maximum Concentration of HSK21542

Time frame: 1 week

Stage I：Half-time (T1/2)

Half-time of HSK21542

Time frame: 1 week

Stage I：Total body clearance following intravenous administration (CL)

Total body clearance following intravenous administration of HSK21542

Time frame: 1 week

Stage I：Volume of distribution following intravenous administration (Vss)

Volume of distribution following intravenous administration of HSK21542

Data from ClinicalTrials.gov

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