A Study of SHR0410 in Hemodialysis Patients With Pruritus

Study Overview
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Brief Summary
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The aim of this study is to evaluate the safety, tolerability and pharmacokinetics of SHR0410 in hemodialysis patients with moderate to severe pruritus

Official Title
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A Randomized, Double-blind, Placebo-controlled, Multiple Ascending Dose Study on Safety, Tolerability and Pharmacokinetics of SHR0410 in Hemodialysis Subjects With Moderate to Severe Pruritus

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: Males or females aged 18-65 (inclusive); Weight (> 50 kg); Patients with end-stage renal disease receiving hemodialysis (including hemodialysis and hemofiltration) three times a week for at least 3 months. VAS≥4 at screening Exclusion Criteria: New York cardiac function classification (NYHA) ≥ level III in the current or previous 6 months; Pruritus caused by other than end-stage renal disease or its complications.. History of malignancy Any physical or mental illness or condition, as determined by the study investigator, that may increase the risk of participating the trial, affect the subject's compliance with the protocol, or affect the subject's completion of the trial Positive urine drug screening; Or a history of drug abuse; Urine test positive for nicotine; Alcohol breath test positive; Alanine aminotransferase (ALT), aspartate aminotransferase (AST) or transglutaminase (GGT) was 1.5 times higher than the upper limit of normal value (ULN), or total bilirubin was 1.5 times higher than the upper limit of normal value (ULN); Screening for hepatitis c antibody (HCVAb), syphilis antibody or human immunodeficiency virus (HIV) antibody positive; Or hepatitis B is active; Abnormal electrocardiogram considered inappropriate to participate in this study by the investigator positive for human chorionic gonadotropin (hCG) blood test A history of allergies to opioids Has used opioids within one week prior to the current visit, or cannot avoid to use opioids other than the study drug during the study period; Change the treatment regimen for pruritus within 14 days, or cannot avoid to change the treatment regimen for pruritus during the study period Received Ultraviolet phototherapy within 14 days before screening visit; Or cannot avoid to receive ultraviolet light therapy during the study. Change the treatment regimen of gabapentin, pregabalin, or duloxetine within 14 days before screening visit; Or the treatment regimen of gabapentin, pregabalin, or duloxetine cannot be avoided to be changed during the study period. Change the treatment regimen of medications within 14 days that may affect the judgment of antipruritic effect; Or the treatment regimen cannot be avoided to be changed during the study Using topical antipruritic drugs, such as creams and patches with moisturizing or antipruritic effects at present. Kidney transplantation is expected during the study period; Subjects who had Participated in this trial (defined by signing the informed consent); Subjects who had Participated in clinical trials of any other drugs within the previous 3 months; Or plan to participate in other drug trials during the trial period; Subjects who had Participated in the clinical trial of any medical device within the previous 3 months; Or participate in other medical device tests during the trial period.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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 low dosage<br> | Drug: SHR0410<br>* administered intravenously<br>* Other names: KOR agonist;|
| Experimental: SHR0410 medium dosage<br> | Drug: SHR0410<br>* administered intravenously<br>* Other names: KOR agonist;|
| Experimental: SHR0410 high dosage<br> | Drug: SHR0410<br>* administered intravenously<br>* Other names: KOR agonist;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* administered intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence and severity of any adverse events that occurred between the first administration and the 48-hour period following the last administration | To evaluate the safety and tolerability of repeated doses of SHR0410 | up to 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under drug-time curve | To evaluate pharmacokinetic (PK) of repeated doses of SHR0410 | up to 7 days | 
| peak time | To evaluate pharmacokinetic (PK) of repeated doses of SHR0410 | up to 7 days | 
| peak concentration | To evaluate pharmacokinetic (PK) of repeated doses of SHR0410 | up to 7 days | 
| half-life | To evaluate pharmacokinetic (PK) of repeated doses of SHR0410 | up to 7 days | 
| apparent clearance rate | To evaluate pharmacokinetic (PK) of repeated doses of SHR0410 | up to 7 days | 
| apparent distribution volume | To evaluate pharmacokinetic (PK) of repeated doses of SHR0410 | up to 7 days | 
| The ratio of AUC0-t after the first and last administration. | To evaluate pharmacokinetic (PK) of repeated doses of SHR0410 | up to 7 days |