A Trial of SHR0410 Injection in Hemodialysis Participants.

Study Overview
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Brief Summary
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This is a multi-site study to evaluate the safety and pharmacokinetics of repeated doses of IV SHR0410 in participants who are undergoing hemodialysis.

Detailed Description
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This is a multi-site study to evaluate the safety and pharmacokinetics of repeated doses of IV SHR0410 in participants who are undergoing hemodialysis. Twenty-four eligible participants will be enrolled into 3 dose cohorts. SHR0410 will be administered after dialysis session. Safety assessments, PK assessments and efficacy evaluations will be performed.

Official Title
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A Phase I, Randomized, Double-blind, Placebo-controlled Study of Intravenous SHR0410 to Evaluate Safety and Pharmacokinetics in Hemodialysis Participants.

Conditions
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Pruritus

Intervention / Treatment
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* Drug: SHR0410
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to understand the study procedures, the risks involved and obtain written informed consent before any study related activity. Male or female between the ages of 18 and 75 years, inclusive. Male subjects with a partner of childbearing potential must be willing to use a condom when sexually active, throughout the study period and for 28 days following last study drug dosing. Female subjects must be post-menopausal for at least 1 year, permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy) or, if of childbearing potential, must be willing to use a highly effective method of contraception throughout the study period and for 28 days following last study drug dosing. Negative drug screen (including alcohol, amphetamines, cocaine, marijuana, opiates, phencyclidine, barbiturates, benzodiazepines, methadone, methamphetamines, tramadol, and tricyclic antidepressants) at screening and on admission to study site. Exclusion Criteria: Anticipated to receive a kidney transplant during the study. Known history of allergic reaction to opiates such as hives (Note: side effects related to the use of opioids such as constipation or nausea would not exclude the participants from the study). Within 12 months prior to screening, known or suspected history of drug abuse or dependence according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR0410 group<br>SHR0410 will be dosed | Drug: SHR0410<br>* drug will be dosed repeatedly<br>|
| Experimental: Placebo<br>Placebo will be dosed | Drug: Placebo<br>* Placebo will be dosed repeatedly<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse events in terms of changes in Hematology | Hemoglobin Hematocrit Erythrocytes count Mean cell volume, Mean cell hemoglobin concentration, Leukocytes count, Neutrophils count, Lymphocytes count, Monocytes count, Eosinophils count, Basophils count, Platelets count | 14 days | 
| Incidence of Adverse events in terms of changes in Urinalysis | Urobilinogen Dipstick urinalysis, including: pH, Specific gravity, Protein, Blood, Leukocytes, Glucose, Ketones, Bilirubin, Nitrites | 14 days | 
| Incidence of Adverse events in terms of changes in Biochemistry | Including Serum creatinine, Urea, Alanine aminotransferase, Aspartate aminotransferase, Gamma glutamyl transferase, Total bilirubin, Total protein, Albumin, Alkaline phosphatase, Serum uric acid, Glucose, Triglycerides, Total cholesterol, High-density lipoprotein cholesterol, Low-density lipoprotein cholesterol | 14 days | 
| Incidence of Adverse events in terms of changes in 12-lead ECGs | The 12-lead ECGs must be recorded after the subjects have rested in the supine position for 5 minutes to ensure a stable baseline | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve (AUC) | Plasma SHR0410 Area Under the Concentration-time Curve (AUC) | Up to 24 hours post dose | 
| Time to the peak plasma concentration (Tmax) | Time to Maximum Plasma SHR0410 Concentration | Up to 24 hours post dose | 
| Peak Plasma Concentration (Cmax) | Peak Plasma SHR0410 Concentration | Up to 24 hours post dose | 
| Half-time (T1/2) | Half-time of SHR0410 | Up to 24 hours post dose |