<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04470154</url>
  </required_header>
  <id_info>
    <org_study_id>HSK21542-203</org_study_id>
    <nct_id>NCT04470154</nct_id>
  </id_info>
  <brief_title>A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of HSK21542 Injection in Subjects Undergoing Hemodialysis</brief_title>
  <official_title>A Multi-center, Randomized, Double-blind, Placebo-controlled Phase II Clinical Trial Evaluating the Safety, Pharmacokinetics, and Efficacy of HSK21542 Injection in Subjects Undergoing Hemodialysis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Haisco Pharmaceutical Group Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Haisco Pharmaceutical Group Co., Ltd.</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multi-center, randomized, double-blind, placebo-controlled phase II clinical trial.&#xD;
      The main objective is to evaluate the safety, pharmacokinetics, and efficacy of HSK21542&#xD;
      injection in subjects undergoing hemodialysis&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a multicenter study, which is divided into two stages. The first stage is a&#xD;
      dose escalation, randomized, double-blind, placebo-controlled study of multiple intravenous&#xD;
      administration within one week in hemodialysis subjects. The second stage is a randomized,&#xD;
      double-blind, placebo-controlled study of Administration for 12 weeks in hemodialysis&#xD;
      subjects with moderate or severe pruritus. In the second stage, consist of a Screening Visit,&#xD;
      a 7-day Run-in Period, a 12 week Double-blind Treatment Period, and a 2-week Discontinuation&#xD;
      Period. Informed consent will be obtained prior to performing any study-specific procedures.&#xD;
      The Screening Visit will occur within 8 to 28 days prior to randomization to assess&#xD;
      eligibility.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 10, 2020</start_date>
  <completion_date type="Actual">October 28, 2021</completion_date>
  <primary_completion_date type="Actual">October 28, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>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.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Stage I：Safety of HSK21542 injection for multiple times within one week in hemodialysis subjects</measure>
    <time_frame>From screening up to D14</time_frame>
    <description>Adverse events (AEs) and serious adverse events (SAEs)，Vital signs、Physical examination, Laboratory examination, ECG</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Stage II：At week 12, the change in weekly average of daily Worst Itch NRS (WI-NRS) from baseline in subjects undergoing hemodialysis</measure>
    <time_frame>12 week</time_frame>
    <description>Change from baseline in average NRS score of itch at week 12</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Stage I：Area under the plasma concentration versus time curve (AUC)</measure>
    <time_frame>1 week</time_frame>
    <description>Plasma HSK21542 Area Under the Concentration-time Curve (AUC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage I：Time to the peak plasma concentration (Tmax)</measure>
    <time_frame>1 week</time_frame>
    <description>Time to Maximum Plasma HSK21542 Concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage I：Maximum Concentration (Cmax)</measure>
    <time_frame>1 week</time_frame>
    <description>Maximum Concentration of HSK21542</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage I：Half-time (T1/2)</measure>
    <time_frame>1 week</time_frame>
    <description>Half-time of HSK21542</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage I：Total body clearance following intravenous administration (CL)</measure>
    <time_frame>1 week</time_frame>
    <description>Total body clearance following intravenous administration of HSK21542</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage I：Volume of distribution following intravenous administration (Vss)</measure>
    <time_frame>1 week</time_frame>
    <description>Volume of distribution following intravenous administration of HSK21542</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage I：trough concentration (Cmin)</measure>
    <time_frame>1 week</time_frame>
    <description>trough concentration of HSK21542</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage I：Change from baseline in average daily Worst Itch NRS (WI-NRS) and Itch-related Quality of Life as Assessed by Skindex-16 Scale Score</measure>
    <time_frame>1 week</time_frame>
    <description>Intensity of itch will be measured using an NRS used to indicate the intensity of the worst itching over the past 24 hours using a 0 to 10 numeric rating scale, where &quot;0&quot; represents &quot;no itching&quot; and &quot;10&quot; represents &quot;worst itching imaginable&quot;.&#xD;
The Skindex-16 Scale is a multidimensional questionnaire which assesses itch-related quality of life over the past week. The questions cover 3 domains: disease, mood/emotional distress, and social functioning domain. The Skindex-16 has 16 questions; the total Skindex-16 score ranges from 0 to 100. A higher total score represents worse quality of life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage I：Correlation between prolactin level and drug exposure of HSK21542 injection in hemodialysis subjects</measure>
    <time_frame>1 week</time_frame>
    <description>Detect prolactin concentration before and after administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage II: Safety of HSK21542 injection in the treatment of moderate and severe pruritus in hemodialysis subjects for 12 weeks</measure>
    <time_frame>12 weeks</time_frame>
    <description>Adverse events (AEs) and serious adverse events (SAEs)，Vital signs、Physical examination, Laboratory examination, ECG</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage II：Area under the plasma concentration versus time curve (AUC)</measure>
    <time_frame>12 weeks</time_frame>
    <description>Plasma Area Under the Concentration-time Curve of HSK21542</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage II：Time to Maximum plasma concentration (Tmax)</measure>
    <time_frame>12 weeks</time_frame>
    <description>Time to Maximum Plasma Concentration of HSK21542</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage II：Maximum Concentration (Cmax)</measure>
    <time_frame>12 weeks</time_frame>
    <description>Maximum Concentration of HSK21542</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage II：Half-time (T1/2)</measure>
    <time_frame>12 weeks</time_frame>
    <description>Half-time (T1/2) of HSK21542</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage II：Total body clearance following intravenous administration (CL)</measure>
    <time_frame>12 weeks</time_frame>
    <description>Total body clearance following intravenous administration of HSK21542</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage II：Volume of distribution following intravenous administration (Vss)</measure>
    <time_frame>12 weeks</time_frame>
    <description>Volume of distribution following intravenous administration of HSK21542</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage II: The proportion of subjects change from baseline ≥3 points with respect to the weekly mean of the daily 24-hour Worst Itching Intensity NRS Score at Week 12</measure>
    <time_frame>12 week</time_frame>
    <description>Intensity of itch will be measured using an NRS used to indicate the intensity of the worst itching over the past 24 hours using a 0 to 10 numeric rating scale, where &quot;0&quot; represents &quot;no itching&quot; and &quot;10&quot; represents &quot;worst itching imaginable&quot;. LS means estimated percent, odds ratio and P value used logistic and Log-binomial regression model.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage II: The proportion of subjects change from baseline ≥4 points with respect to the weekly mean of the daily 24-hour Worst Itching Intensity NRS Score at Week 12</measure>
    <time_frame>12 week</time_frame>
    <description>Intensity of itch will be measured using an NRS used to indicate the intensity of the worst itching over the past 24 hours using a 0 to 10 numeric rating scale, where &quot;0&quot; represents &quot;no itching&quot; and &quot;10&quot; represents &quot;worst itching imaginable&quot;. LS means estimated percent, odds ratio and P value used logistic and Log-binomial regression model.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage II：Change from baseline in Itch-related Quality of Life as Assessed by Skindex-16 and 5-D Scale Score</measure>
    <time_frame>12 week</time_frame>
    <description>The Skindex-16 Scale is a multidimensional questionnaire which assesses itch-related quality of life over the past week. The questions cover 3 domains: disease, mood/emotional distress, and social functioning domain. The Skindex-16 has 16 questions; the total Skindex-16 score ranges from 0 to 100. A higher total score represents worse quality of life.&#xD;
The 5-D Itch Scale is a multidimensional questionnaire which assesses itch-related quality of life over the past 2 weeks. The questions cover five dimensions of itch including the duration of itch/day, degree, direction (improvement/worsening), disability (impact on activities such as work), and body distribution of itch. The 5-D Itch Scale has 5 questions; the total 5-D Itch Scale score ranges from 5 to 25, with higher scores indicating worse responses.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage II: Weekly mean value of the daily 24-hour Worst Itching Intensity NRS Score within 2 weeks after drug withdrawal after 12 weeks of administration</measure>
    <time_frame>14 week</time_frame>
    <description>Intensity of itch will be measured using an NRS used to indicate the intensity of the worst itching over the past 24 hours using a 0 to 10 numeric rating scale, where &quot;0&quot; represents &quot;no itching&quot; and &quot;10&quot; represents &quot;worst itching imaginable&quot;.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage II: Weekly mean value of the ShOWS and OOWS Score within 2 weeks after drug withdrawal after 12 weeks of administration</measure>
    <time_frame>14 week</time_frame>
    <description>According to the weekly mean of ShOWS and OOWS scores, combined with AE, comprehensively evaluate whether there is drug withdrawal reaction.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage II: Change from baseline in the level of serum IL-6，IL-31，TNF-α，and hs-CRP</measure>
    <time_frame>12 weeks</time_frame>
    <description>Evaluate the effect of HSK21542 on IL-6, IL-31, TNF- α and hs-CRP levels.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage II: Change from baseline in the level of serum iPTH</measure>
    <time_frame>12 weeks</time_frame>
    <description>Evaluate the effect of HSK21542 on iPTH levels.</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">131</enrollment>
  <condition>Uremic Pruritus</condition>
  <arm_group>
    <arm_group_label>Stage I: 0.05 μg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>IV HSK21542 0.05 μg/kg solution（active or placebo） administered after each dialysis session within 2h±30 min (3 times/week).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stage I: 0.15 μg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>IV HSK21542 0.15 μg/kg solution（active or placebo） administered after each dialysis session within 2h±30 min (3 times/week).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stage I: 0.30 μg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>IV HSK21542 0.30 μg/kg solution（active or placebo） administered after each dialysis session within 2h±30 min (3 times/week).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stage I: 0.80 μg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>IV HSK21542 0.80 μg/kg solution（active or placebo） administered after each dialysis session within 2h±30 min (3 times/week).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stage II: 0.3 μg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>IV HSK21542 0.3 μg/kg solution（active or placebo） administered after each dialysis session within 10 min (3 times/week).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stage II: 0.6 μg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>IV HSK21542 0.3 μg/kg solution（active or placebo） administered after each dialysis session within 10 min (3 times/week).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Stage I:HSK21542 0.05 μg/kg</intervention_name>
    <description>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</description>
    <arm_group_label>Stage I: 0.05 μg/kg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Stage I:HSK21542 0.15 μg/kg</intervention_name>
    <description>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</description>
    <arm_group_label>Stage I: 0.15 μg/kg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Stage I:HSK21542 0.30 μg/kg</intervention_name>
    <description>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</description>
    <arm_group_label>Stage I: 0.30 μg/kg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Stage I:HSK21542 0.80 μg/kg</intervention_name>
    <description>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</description>
    <arm_group_label>Stage I: 0.80 μg/kg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Stage II:HSK21542 0.3 μg/kg</intervention_name>
    <description>Randomized to HSK21542 0.3 μg/kg or 0.6 μg/kg or the corresponding placebo group</description>
    <arm_group_label>Stage II: 0.3 μg/kg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Stage II:HSK21542 0.6 μg/kg</intervention_name>
    <description>Randomized to HSK21542 0.3 μg/kg or 0.6 μg/kg or the corresponding placebo group</description>
    <arm_group_label>Stage II: 0.6 μg/kg</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Stage1: Inclusion Criteria:&#xD;
&#xD;
          1. Subjects who are willing to sign an informed consent form, fully understand the&#xD;
             objectives and purposes of the study, and are willing to comply with the study&#xD;
             protocol before any of the study-related procedures start;&#xD;
&#xD;
          2. Aged ≥ 18 and ≤ 75 years old, male or female;&#xD;
&#xD;
          3. Dry weight ≥ 50.0 kg at screening, body mass index (BMI = weight (kg) / height2 [m2])&#xD;
             in the range of 16.0-30.0 kg/m^2 (inclusive);&#xD;
&#xD;
          4. Patients with end-stage renal diseases who receive hemodialysis (including&#xD;
             hemodiafiltration) 3 times in a week prior to screening for at least 3 months;&#xD;
&#xD;
          5. Patients with at least two occurrences of single-compartment urea clearance (sp Kt/V,&#xD;
             see Appendix 7 for the calculation formula) ≥ 1.2, or at least two occurrences of urea&#xD;
             reduction ratio (URR) ≥ 65%, or one occurrence of sp Kt/V ≥ 1.2 and one occurrence of&#xD;
             URR ≥ 65% on different days of dialysis within 3 months before screening;&#xD;
&#xD;
          6. Male subjects must agree to use condoms in sexual intercourse during the study and&#xD;
             within 3 months after the last dose; female subjects should have had menopause for at&#xD;
             least one year, or should have had permanent sterilization (e.g., fallopian tube&#xD;
             occlusion, hysterectomy, bilateral salpingectomy); or women of childbearing potential&#xD;
             must agree to take effective contraceptive measures during the study and within 3&#xD;
             months after the last dose, such as oral contraceptives, condoms, and contraceptive&#xD;
             films.&#xD;
&#xD;
        Stage1: Exclusion Criteria:&#xD;
&#xD;
          1. Expected to undergo kidney transplantation and/or parathyroidectomy during the study;&#xD;
&#xD;
          2. History of allergy to opioids, such as urticaria (Note: adverse effects related to&#xD;
             opioid use, such as constipation and nausea, are not included as the exclusion&#xD;
             criteria in this study);&#xD;
&#xD;
          3. Used opioids within one week before screening, or unable to avoid the use of opioids&#xD;
             other than the investigational product during the study;&#xD;
&#xD;
          4. Participated in any clinical trial of other drug or medical device within 1 month&#xD;
             before screening (received study medication or treated by the medical device in the&#xD;
             clinical trial);&#xD;
&#xD;
          5. Used blood perfusion within 3 months before screening;&#xD;
&#xD;
          6. History of medication or drug abuse;&#xD;
&#xD;
          7. Average daily alcohol consumption greater than 15 g (15 g of alcohol is equivalent to&#xD;
             450 mL of beer or 150 mL of wine or 50 mL of light liquor) within 3 months before&#xD;
             screening;&#xD;
&#xD;
          8. Unable to comply with the standard dietary plan and unable to avoid coffee or tea&#xD;
             during the study;&#xD;
&#xD;
          9. Blood pressure of upper limbs in the supine position at screening: systolic blood&#xD;
             pressure &lt; 90 mmHg, or diastolic blood pressure &lt; 60 mmHg, or systolic blood pressure&#xD;
             &gt; 180 mmHg, or diastolic blood pressure &gt; 110 mmHg;&#xD;
&#xD;
         10. New York Heart Association (NYHA) Class ≥ III at screening; or confirmed to have&#xD;
             abnormal ECG at screening and determined by the investigator to be inappropriate to be&#xD;
             enrolled, including QTcF ≥ 480 ms;&#xD;
&#xD;
         11. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or total bilirubin&#xD;
             ≥ 1.5 × upper limit of normal (ULN) at screening;&#xD;
&#xD;
         12. Blood sodium &gt; 155 mmol/L at screening;&#xD;
&#xD;
         13. Hemoglobin ≤ 80 g/L at screening;&#xD;
&#xD;
         14. Positive for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCVAb),&#xD;
             syphilis antibody, or human immunodeficiency virus (HIV) antibody at screening;&#xD;
&#xD;
         15. Underwent major surgery (determined by the investigator as major surgery) within 3&#xD;
             months before screening;&#xD;
&#xD;
         16. Having a total blood loss of ≥ 200mL within 1 month before screening, except for the&#xD;
             blood loss during menstruation in females;&#xD;
&#xD;
         17. Females who are pregnant or breastfeeding;&#xD;
&#xD;
         18. Any physiological or psychological diseases or conditions that may increase the risk&#xD;
             of the trial, affect the subject's compliance with the protocol, or affect the&#xD;
             subject's completion of the trial, as judged by the study physician, including but not&#xD;
             limited to:&#xD;
&#xD;
               1. Severe mental illness or cognitive impairment (e.g., dementia);&#xD;
&#xD;
               2. Any other relevant acute or chronic neurological and psychiatric diseases (e.g.,&#xD;
                  encephalopathy, coma, delirium) within 3 months before screening;&#xD;
&#xD;
               3. Patients with malignant tumors (including malignant tumors that have been cured&#xD;
                  without recurrence).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Guizhou Medical University Affiliated Hospital</name>
      <address>
        <city>Guiyang</city>
        <state>Guizhou</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>July 7, 2020</study_first_submitted>
  <study_first_submitted_qc>July 13, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 14, 2020</study_first_posted>
  <last_update_submitted>August 4, 2022</last_update_submitted>
  <last_update_submitted_qc>August 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 9, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pruritus</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04470154
org study id: HSK21542-203
nct id: NCT04470154
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
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.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: 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.
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Stage I：Safety of HSK21542 injection for multiple times within one week in hemodialysis subjects
time frame: From screening up to D14
description: Adverse events (AEs) and serious adverse events (SAEs)，Vital signs、Physical examination, Laboratory examination, ECG
measure: Stage II：At week 12, the change in weekly average of daily Worst Itch NRS (WI-NRS) from baseline in subjects undergoing hemodialysis
time frame: 12 week
description: Change from baseline in average NRS score of itch at week 12
measure: Stage I：Area under the plasma concentration versus time curve (AUC)
time frame: 1 week
description: Plasma HSK21542 Area Under the Concentration-time Curve (AUC)
measure: Stage I：Time to the peak plasma concentration (Tmax)
time frame: 1 week
description: Time to Maximum Plasma HSK21542 Concentration
measure: Stage I：Maximum Concentration (Cmax)
time frame: 1 week
description: Maximum Concentration of HSK21542
measure: Stage I：Half-time (T1/2)
time frame: 1 week
description: Half-time of HSK21542
measure: Stage I：Total body clearance following intravenous administration (CL)
time frame: 1 week
description: Total body clearance following intravenous administration of HSK21542
measure: Stage I：Volume of distribution following intravenous administration (Vss)
time frame: 1 week
description: Volume of distribution following intravenous administration of HSK21542
measure: Stage I：trough concentration (Cmin)
time frame: 1 week
description: trough concentration of HSK21542
measure: Stage I：Change from baseline in average daily Worst Itch NRS (WI-NRS) and Itch-related Quality of Life as Assessed by Skindex-16 Scale Score
time frame: 1 week
description: Intensity of itch will be measured using an NRS used to indicate the intensity of the worst itching over the past 24 hours using a 0 to 10 numeric rating scale, where "0" represents "no itching" and "10" represents "worst itching imaginable".
The Skindex-16 Scale is a multidimensional questionnaire which assesses itch-related quality of life over the past week. The questions cover 3 domains: disease, mood/emotional distress, and social functioning domain. The Skindex-16 has 16 questions; the total Skindex-16 score ranges from 0 to 100. A higher total score represents worse quality of life.
measure: Stage I：Correlation between prolactin level and drug exposure of HSK21542 injection in hemodialysis subjects
time frame: 1 week
description: Detect prolactin concentration before and after administration
measure: Stage II: Safety of HSK21542 injection in the treatment of moderate and severe pruritus in hemodialysis subjects for 12 weeks
time frame: 12 weeks
description: Adverse events (AEs) and serious adverse events (SAEs)，Vital signs、Physical examination, Laboratory examination, ECG
measure: Stage II：Area under the plasma concentration versus time curve (AUC)
time frame: 12 weeks
description: Plasma Area Under the Concentration-time Curve of HSK21542
measure: Stage II：Time to Maximum plasma concentration (Tmax)
time frame: 12 weeks
description: Time to Maximum Plasma Concentration of HSK21542
measure: Stage II：Maximum Concentration (Cmax)
time frame: 12 weeks
description: Maximum Concentration of HSK21542
measure: Stage II：Half-time (T1/2)
time frame: 12 weeks
description: Half-time (T1/2) of HSK21542
measure: Stage II：Total body clearance following intravenous administration (CL)
time frame: 12 weeks
description: Total body clearance following intravenous administration of HSK21542
measure: Stage II：Volume of distribution following intravenous administration (Vss)
time frame: 12 weeks
description: Volume of distribution following intravenous administration of HSK21542
measure: Stage II: The proportion of subjects change from baseline ≥3 points with respect to the weekly mean of the daily 24-hour Worst Itching Intensity NRS Score at Week 12
time frame: 12 week
description: Intensity of itch will be measured using an NRS used to indicate the intensity of the worst itching over the past 24 hours using a 0 to 10 numeric rating scale, where "0" represents "no itching" and "10" represents "worst itching imaginable". LS means estimated percent, odds ratio and P value used logistic and Log-binomial regression model.
measure: Stage II: The proportion of subjects change from baseline ≥4 points with respect to the weekly mean of the daily 24-hour Worst Itching Intensity NRS Score at Week 12
time frame: 12 week
description: Intensity of itch will be measured using an NRS used to indicate the intensity of the worst itching over the past 24 hours using a 0 to 10 numeric rating scale, where "0" represents "no itching" and "10" represents "worst itching imaginable". LS means estimated percent, odds ratio and P value used logistic and Log-binomial regression model.
measure: Stage II：Change from baseline in Itch-related Quality of Life as Assessed by Skindex-16 and 5-D Scale Score
time frame: 12 week
description: The Skindex-16 Scale is a multidimensional questionnaire which assesses itch-related quality of life over the past week. The questions cover 3 domains: disease, mood/emotional distress, and social functioning domain. The Skindex-16 has 16 questions; the total Skindex-16 score ranges from 0 to 100. A higher total score represents worse quality of life.
The 5-D Itch Scale is a multidimensional questionnaire which assesses itch-related quality of life over the past 2 weeks. The questions cover five dimensions of itch including the duration of itch/day, degree, direction (improvement/worsening), disability (impact on activities such as work), and body distribution of itch. The 5-D Itch Scale has 5 questions; the total 5-D Itch Scale score ranges from 5 to 25, with higher scores indicating worse responses.
measure: Stage II: Weekly mean value of the daily 24-hour Worst Itching Intensity NRS Score within 2 weeks after drug withdrawal after 12 weeks of administration
time frame: 14 week
description: Intensity of itch will be measured using an NRS used to indicate the intensity of the worst itching over the past 24 hours using a 0 to 10 numeric rating scale, where "0" represents "no itching" and "10" represents "worst itching imaginable".
measure: Stage II: Weekly mean value of the ShOWS and OOWS Score within 2 weeks after drug withdrawal after 12 weeks of administration
time frame: 14 week
description: According to the weekly mean of ShOWS and OOWS scores, combined with AE, comprehensively evaluate whether there is drug withdrawal reaction.
measure: Stage II: Change from baseline in the level of serum IL-6，IL-31，TNF-α，and hs-CRP
time frame: 12 weeks
description: Evaluate the effect of HSK21542 on IL-6, IL-31, TNF- α and hs-CRP levels.
measure: Stage II: Change from baseline in the level of serum iPTH
time frame: 12 weeks
description: Evaluate the effect of HSK21542 on iPTH levels.
arm group label: Stage I: 0.05 μg/kg
arm group type: Experimental
description: IV HSK21542 0.05 μg/kg solution（active or placebo） administered after each dialysis session within 2h±30 min (3 times/week).
arm group label: Stage I: 0.15 μg/kg
arm group type: Experimental
description: IV HSK21542 0.15 μg/kg solution（active or placebo） administered after each dialysis session within 2h±30 min (3 times/week).
arm group label: Stage I: 0.30 μg/kg
arm group type: Experimental
description: IV HSK21542 0.30 μg/kg solution（active or placebo） administered after each dialysis session within 2h±30 min (3 times/week).
arm group label: Stage I: 0.80 μg/kg
arm group type: Experimental
description: IV HSK21542 0.80 μg/kg solution（active or placebo） administered after each dialysis session within 2h±30 min (3 times/week).
arm group label: Stage II: 0.3 μg/kg
arm group type: Experimental
description: IV HSK21542 0.3 μg/kg solution（active or placebo） administered after each dialysis session within 10 min (3 times/week).
arm group label: Stage II: 0.6 μg/kg
arm group type: Experimental
description: IV HSK21542 0.3 μg/kg solution（active or placebo） administered after each dialysis session within 10 min (3 times/week).
intervention type: Drug
intervention name: Stage I:HSK21542 0.05 μg/kg
description: 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
arm group label: Stage I: 0.05 μg/kg
intervention type: Drug
intervention name: Stage I:HSK21542 0.15 μg/kg
description: 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
arm group label: Stage I: 0.15 μg/kg
intervention type: Drug
intervention name: Stage I:HSK21542 0.30 μg/kg
description: 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
arm group label: Stage I: 0.30 μg/kg
intervention type: Drug
intervention name: Stage I:HSK21542 0.80 μg/kg
description: 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
arm group label: Stage I: 0.80 μg/kg
intervention type: Drug
intervention name: Stage II:HSK21542 0.3 μg/kg
description: Randomized to HSK21542 0.3 μg/kg or 0.6 μg/kg or the corresponding placebo group
arm group label: Stage II: 0.3 μg/kg
intervention type: Drug
intervention name: Stage II:HSK21542 0.6 μg/kg
description: Randomized to HSK21542 0.3 μg/kg or 0.6 μg/kg or the corresponding placebo group
arm group label: Stage II: 0.6 μg/kg
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
country: China
responsible party type: Sponsor
mesh term: Pruritus