A Study of SHR4010 in Patients With Hemodialysis

A Phase I, Open-label Clinical Study on Safety and Pharmacokinetics of SHR0410 Injection for Multiple Administration in Hemodialysis Patients

The study is being conducted to evaluate the safety and pharmacokinetics of SHR0410 in patients with hemodialysis.

Study Overview

• Status: Completed
• Conditions: Pruritus
• Intervention / Treatment: Drug: SHR0410

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Zhongda Hospital Affiliated to Southeast University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Able to understand the study procedures, the risks involved and obtain written informed consent before any study related activity;
2. Male or female between the ages of 18 and 65 years, inclusive;
3. A total body weight ≥ 50 kg;
4. End stage of renal disease (ESRD) participants who have been on hemodialysis (including hemodiafiltration) for at least six months and are currently on hemodialysis (including hemodiafiltration) three times a week.
5. 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, and enter the trial only after menstruation is confirmed..

Exclusion Criteria:

1. Anticipated to receive a kidney transplant during the study;
2. 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);
3. History of drug abuse in the past;
4. Nicotine test positive;
5. Alcohol breath test was positive;
6. The average daily intake of alcohol in the three months before screening was more than 15 g (15 g alcohol equivalent to 450 ml beer or 150 ml wine or 50 ml low-alcohol liquor).
7. Could not obey the unified dietary arrangements and avoid taking coffee or tea during the study period;
8. Blood pressure of upper limbs in supine position was : systolic pressure < 110 mmHg, diastolic pressure < 70 mmHg or systolic pressure > 180 mmHg, diastolic pressure > 110 mmHg at screening or pre-dosing after confirmation in a repeat test;
9. New York Heart Function Classification (NYHA) > III in the screening stage, or abnormal electrocardiogram with clinical significance judged by researchers in the screening stage , including QTcF > 480ms;
10. Screening alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase > 1.5 × ULN, or total bilirubin> 1.5 × ULN.
11. Positive at screening for human immunodeficiency virus (HIV) antibody, Hepatitis B surface antigen (HBsAg), or Hepatitis C virus (HCV) antibody.
12. Undergone major surgery within 3 months prior to screening.
13. Total blood loss ≥ 200 ml within 30 days prior to screening, excluding female bleeding during physiological period.
14. Blood human chorionic gonadotropin (hCG) test was positive.
15. Opioids were used within a week before screening, or opioids other than research drugs could not be avoided during the study period.
16. Previous participation in this trial, as defined by signing informed consent form;
17. Participation defined as administration of investigational drugs in another clinical trial (including trial with medical devices) 3 months before screening, or currently participating in another clinical trial (including medical device trials);
18. Any other medical or psychological condition, which in the opinion of the Investigator, might create undue risk to the participant or interfere with the participant's ability to comply with the protocol requirements, or to complete the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SHR0410; Experimental: SHR0410 dose escalation.	Drug: SHR0410; SHR0410 monotherapy,given intravenously; Other Names: KOR agonist

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability])	Pre-dose to Day13

Secondary Outcome Measures

Outcome Measure	Time Frame
Assessment of PK parameter-Area under drug-time curve (AUC0-t)	Pre-dose to Day 6
Assessment of PK parameter-Area under drug-time curve (AUC0-∝)	Pre-dose to Day 6
Assessment of PK parameter-peak time (Tmax)	Pre-dose to Day 6
Assessment of PK parameter-peak concentration (Cmax)	Pre-dose to Day 6
Assessment of PK parameter-half-life (t1/2)	Pre-dose to Day 6
Assessment of PK parameter-pparent clearance rate (CL)	Pre-dose to Day 6
Assessment of PK parameter-apparent distribution volume (Vz)	Pre-dose to Day 6
Pharmacokinetic-The ratio of AUC0-t after the first and last administration.	Pre-dose to Day 6
The renal clearance rate of SHR0410 in urine after each administration.	Pre-dose to Day 6
The cumulative excretion rate of SHR0410 in urine after each administration.	Pre-dose to Day 6

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Study Director: Jianjun Zou, Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2019
• Primary Completion (Actual): April 20, 2020
• Study Completion (Actual): June 15, 2020

Study Registration Dates

• First Submitted: August 28, 2019
• First Submitted That Met QC Criteria: September 20, 2019
• First Posted (Actual): September 23, 2019

Study Record Updates

• Last Update Posted (Actual): August 18, 2022
• Last Update Submitted That Met QC Criteria: August 17, 2022
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Manifestations; Pruritus
• Other Study ID Numbers: SHR0410-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No