- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04470154
A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of HSK21542 Injection in Subjects Undergoing Hemodialysis
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
Study Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Guizhou
-
Guiyang, Guizhou, China
- Guizhou Medical University Affiliated Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Stage1: Inclusion Criteria:
- 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;
- Aged ≥ 18 and ≤ 75 years old, male or female;
- 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);
- Patients with end-stage renal diseases who receive hemodialysis (including hemodiafiltration) 3 times in a week prior to screening for at least 3 months;
- 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;
- 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:
- Expected to undergo kidney transplantation and/or parathyroidectomy during the study;
- 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);
- Used opioids within one week before screening, or unable to avoid the use of opioids other than the investigational product during the study;
- 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);
- Used blood perfusion within 3 months before screening;
- History of medication or drug abuse;
- 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;
- Unable to comply with the standard dietary plan and unable to avoid coffee or tea during the study;
- 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;
- 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;
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or total bilirubin ≥ 1.5 × upper limit of normal (ULN) at screening;
- Blood sodium > 155 mmol/L at screening;
- Hemoglobin ≤ 80 g/L at screening;
- Positive for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCVAb), syphilis antibody, or human immunodeficiency virus (HIV) antibody at screening;
- Underwent major surgery (determined by the investigator as major surgery) within 3 months before screening;
- Having a total blood loss of ≥ 200mL within 1 month before screening, except for the blood loss during menstruation in females;
- Females who are pregnant or breastfeeding;
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:
- Severe mental illness or cognitive impairment (e.g., dementia);
- Any other relevant acute or chronic neurological and psychiatric diseases (e.g., encephalopathy, coma, delirium) within 3 months before screening;
- Patients with malignant tumors (including malignant tumors that have been cured without recurrence).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Stage I: 0.05 μg/kg
IV HSK21542 0.05 μg/kg solution(active or placebo) administered after each dialysis session within 2h±30 min (3 times/week).
|
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
|
EXPERIMENTAL: Stage I: 0.15 μg/kg
IV HSK21542 0.15 μg/kg solution(active or placebo) administered after each dialysis session within 2h±30 min (3 times/week).
|
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
|
EXPERIMENTAL: Stage I: 0.30 μg/kg
IV HSK21542 0.30 μg/kg solution(active or placebo) administered after each dialysis session within 2h±30 min (3 times/week).
|
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
|
EXPERIMENTAL: Stage I: 0.80 μg/kg
IV HSK21542 0.80 μg/kg solution(active or placebo) administered after each dialysis session within 2h±30 min (3 times/week).
|
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
|
EXPERIMENTAL: Stage II: 0.3 μg/kg
IV HSK21542 0.3 μg/kg solution(active or placebo) administered after each dialysis session within 10 min (3 times/week).
|
Randomized to HSK21542 0.3 μg/kg or 0.6 μg/kg or the corresponding placebo group
|
EXPERIMENTAL: Stage II: 0.6 μg/kg
IV HSK21542 0.3 μg/kg solution(active or placebo) administered after each dialysis session within 10 min (3 times/week).
|
Randomized to HSK21542 0.3 μg/kg or 0.6 μg/kg or the corresponding placebo group
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Stage I:Safety of HSK21542 injection for multiple times within one week in hemodialysis subjects
Time Frame: From screening up to D14
|
Adverse events (AEs) and serious adverse events (SAEs),Vital signs、Physical examination, Laboratory examination, ECG
|
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
Time Frame: 12 week
|
Change from baseline in average NRS score of itch at week 12
|
12 week
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Stage I:Area under the plasma concentration versus time curve (AUC)
Time Frame: 1 week
|
Plasma HSK21542 Area Under the Concentration-time Curve (AUC)
|
1 week
|
Stage I:Time to the peak plasma concentration (Tmax)
Time Frame: 1 week
|
Time to Maximum Plasma HSK21542 Concentration
|
1 week
|
Stage I:Maximum Concentration (Cmax)
Time Frame: 1 week
|
Maximum Concentration of HSK21542
|
1 week
|
Stage I:Half-time (T1/2)
Time Frame: 1 week
|
Half-time of HSK21542
|
1 week
|
Stage I:Total body clearance following intravenous administration (CL)
Time Frame: 1 week
|
Total body clearance following intravenous administration of HSK21542
|
1 week
|
Stage I:Volume of distribution following intravenous administration (Vss)
Time Frame: 1 week
|
Volume of distribution following intravenous administration of HSK21542
|
1 week
|
Stage I:trough concentration (Cmin)
Time Frame: 1 week
|
trough concentration of HSK21542
|
1 week
|
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
|
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. |
1 week
|
Stage I:Correlation between prolactin level and drug exposure of HSK21542 injection in hemodialysis subjects
Time Frame: 1 week
|
Detect prolactin concentration before and after administration
|
1 week
|
Stage II: Safety of HSK21542 injection in the treatment of moderate and severe pruritus in hemodialysis subjects for 12 weeks
Time Frame: 12 weeks
|
Adverse events (AEs) and serious adverse events (SAEs),Vital signs、Physical examination, Laboratory examination, ECG
|
12 weeks
|
Stage II:Area under the plasma concentration versus time curve (AUC)
Time Frame: 12 weeks
|
Plasma Area Under the Concentration-time Curve of HSK21542
|
12 weeks
|
Stage II:Time to Maximum plasma concentration (Tmax)
Time Frame: 12 weeks
|
Time to Maximum Plasma Concentration of HSK21542
|
12 weeks
|
Stage II:Maximum Concentration (Cmax)
Time Frame: 12 weeks
|
Maximum Concentration of HSK21542
|
12 weeks
|
Stage II:Half-time (T1/2)
Time Frame: 12 weeks
|
Half-time (T1/2) of HSK21542
|
12 weeks
|
Stage II:Total body clearance following intravenous administration (CL)
Time Frame: 12 weeks
|
Total body clearance following intravenous administration of HSK21542
|
12 weeks
|
Stage II:Volume of distribution following intravenous administration (Vss)
Time Frame: 12 weeks
|
Volume of distribution following intravenous administration of HSK21542
|
12 weeks
|
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
|
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.
|
12 week
|
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
|
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.
|
12 week
|
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
|
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. |
12 week
|
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
|
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".
|
14 week
|
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
|
According to the weekly mean of ShOWS and OOWS scores, combined with AE, comprehensively evaluate whether there is drug withdrawal reaction.
|
14 week
|
Stage II: Change from baseline in the level of serum IL-6,IL-31,TNF-α,and hs-CRP
Time Frame: 12 weeks
|
Evaluate the effect of HSK21542 on IL-6, IL-31, TNF- α and hs-CRP levels.
|
12 weeks
|
Stage II: Change from baseline in the level of serum iPTH
Time Frame: 12 weeks
|
Evaluate the effect of HSK21542 on iPTH levels.
|
12 weeks
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- HSK21542-203
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Uremic Pruritus
-
Thammasat University HospitalCompletedUremic PruritusThailand
-
Conmed Pharmaceutical & Bio-Medical CorporationChang Gung Memorial Hospital; Kaohsiung Medical University; Tri-Service General... and other collaboratorsCompleted
-
Kissei Pharmaceutical Co., Ltd.Maruishi PharmaceuticalCompleted
-
Chang Gung Memorial HospitalUnknown
-
Lumosa Therapeutics Co., Ltd.Unknown
-
Kissei Pharmaceutical Co., Ltd.Completed
-
Toray Industries, IncCompletedUremic PruritusBulgaria, Germany
-
Cara Therapeutics, Inc.CompletedPruritus | Uremic PruritusUnited States
-
Shenyang Sunshine Pharmaceutical Co., LTD.UnknownUremic PruritusChina
-
Cara Therapeutics, Inc.CompletedUremic PruritusUnited States
Clinical Trials on Stage I:HSK21542 0.05 μg/kg
-
Haisco Pharmaceutical Group Co., Ltd.Completed
-
Haisco Pharmaceutical Group Co., Ltd.Completed
-
Sichuan Haisco Pharmaceutical Group Co., LtdSecond Affiliated Hospital, School of Medicine, Zhejiang UniversityCompletedHealthy VolunteersChina
-
AstraZenecaCompleted
-
Daiichi Sankyo, Inc.CompletedCachexiaUnited States, Argentina, Chile, Guatemala, Honduras, Romania
-
General Hospital of Ningxia Medical UniversityCompleted
-
Trinomab Biotech Co., Ltd.TIGERMED AUSTRALIA PTY LIMITEDCompletedHealthy Adult SubjectsAustralia
-
Jiangsu HengRui Medicine Co., Ltd.CompletedBreast Cancer | Neutropenia | Febrile NeutropeniaChina
-
NuvOx LLCUniversity of ArkansasCompleted
-
GuerbetCompletedChronic Liver Disease | HepatoCellular CarcinomaFrance