Safety and Pharmacokinetics of HRS-1780 in Healthy Subjects and Subjects With Impaired Renal Function

A Multicenter, Non-randomized, Open-label, Parallel-controlled Study to Evaluate the Safety and Pharmacokinetics of HRS-1780 in Healthy Subjects and Subjects With Impaired Renal Function

This is a multicenter, non-randomized, open-label, parallel-controlled study. The main objective is to evaluate the safety and pharmacokinetics of HRS-1780 in subjects with mild and moderate renal impairment versus healthy subjects, and to provide a basis for dose selection of HRS-1780 in patients with chronic kidney disease.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Drug: HRS-1780

• Study Type: Interventional
• Enrollment (Estimated): 27
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yue Fei; Phone Number: 0518-82342973; Email: yue.fei@hengrui.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

- Healthy subjects：

1. Able to understand the trial procedures and possible risks, volunteers to participate in the trial, willing and able to comply with all scheduled visits and study procedures, and provides written informed consent.;
2. Male and female, 18 to 70 years of age, inclusive;
3. Body mass index (BMI) between 18.0 and 32.0 kg/m2, inclusive;
4. Normal glomerular filtration rate;
5. No clinically significant abnormalities in physical examination, vital signs, laboratory tests, 12-lead ECG, etc. at the investigator's discretion;
6. Men and WOCBP must agree to take highly effective contraceptive methods detailed in the protocol, have no plan to have a child from signing the consent form until at least one month after IP administration, and must not undertake for sperm/egg donation. Female participants should not be lactating.

Renal impairment subjects：

1. Able to understand the trial procedures and possible risks, volunteers to participate in the trial, willing and able to comply with all scheduled visits and study procedures, and provides written informed consent.;
2. Male and female, 18 to 70 years of age, inclusive;
3. Body mass index (BMI) between 18.0 and 32.0 kg/m2, inclusive;
4. Glomerular filtration rate between 30 to 89 mL/min, inclusive;
5. Except for renal impairment and related complications, no clinically significant abnormalities in physical examination, vital signs, laboratory tests, 12-lead ECG, etc. at the investigator's discretion;
6. Men and WOCBP must agree to take highly effective contraceptive methods detailed in the protocol, have no plan to have a child from signing the consent form until at least one month after IP administration, and must not undertake for sperm/egg donation. Female participants should not be lactating.

Exclusion Criteria:

- Healthy subjects：

1. Known history or suspected of being allergic to study drug or any component of it, or significant allergic reactions to other biologic products and drugs, or severe food allergies;
2. Clinically significant abnormalities in 12-Lead ECG;
3. Severe infections, injuries, or major surgeries as determined by the investigator within 3 months prior to screening, or plans to have surgeries during the study;
4. Receipt of medical devices or another investigational drug (including placebo) within 3 months or 5 half-lives, whichever is longer prior to screening, or plans to participate in another clinical study during this study;
5. Use of any prescription medicine, over-the-counter medicine, herbal remedy, or nutritional supplement within 2 weeks prior to screening;
6. Consumption of more than 14 units of alcohol per week within 6 months prior to screening, or incapable to refrain from consuming alcohol during the study, or positive alcohol breath test result;
7. Consumption of more than 5 cigarettes daily (or products with an equivalent amount of nicotine) within 3 months prior to screening, or use of any tobacco products 48 hours prior to dosing;
8. History of illicit or prescription drug abuse or addiction in the past 5 years, or illicit or prescription drug abuse within 3 months prior to screening, or positive urine drug screen;
9. Unwilling or unable to comply with the contraceptive methods detailed in this protocol;
10. Positive hepatitis B virus, hepatitis B core antibody, hepatitis C virus, human immunodeficiency virus, or syphilis at screening;
11. History or evidence of clinically significant disorders and deemed not suitable to participate in the study by the investigator within 6 months prior to screening;
12. Inability to tolerate venipuncture blood collection;
13. Any other circumstances that, in the investigator's judgment, may increase the risk to the subject, or associated with the subject's participation in and completion of the study.

Renal impairment subjects：

1. History of kidney transplant or plan to receive a kidney transplant during the trial;
2. Known history or suspected of being allergic to study drug or any component of it, or significant allergic reactions to other biologic products and drugs, or severe food allergies;
3. Clinically significant abnormalities in 12-Lead ECG;
4. Severe infections, injuries, or major surgeries as determined by the investigator within 3 months prior to screening, or plans to have surgeries during the study;
5. Receipt of medical devices or another investigational drug (including placebo) within 3 months or 5 half-lives, whichever is longer prior to screening, or plans to participate in another clinical study during this study;
6. Except for treatment of renal impairment and related complications, use of other prescription medicine, over-the-counter medicine, herbal remedy, or nutritional supplement within 2 weeks prior to screening;
7. Consumption of more than 14 units of alcohol per week within 6 months prior to screening, or incapable to refrain from consuming alcohol during the study, or positive alcohol breath test result;
8. Consumption of more than 5 cigarettes daily (or products with an equivalent amount of nicotine) within 3 months prior to screening, or use of any tobacco products 48 hours prior to dosing;
9. History of illicit or prescription drug abuse or addiction in the past 5 years, or illicit or prescription drug abuse within 3 months prior to screening, or positive urine drug screen;
10. Unwilling or unable to comply with the contraceptive methods detailed in this protocol;
11. Positive hepatitis B virus, hepatitis B core antibody, hepatitis C virus, human immunodeficiency virus, or syphilis at screening;
12. History or evidence of clinically significant disorders and deemed not suitable to participate in the study by the investigator within 6 months prior to screening;
13. Inability to tolerate venipuncture blood collection;
14. Any other circumstances that, in the investigator's judgment, may increase the risk to the subject, or associated with the subject's participation in and completion of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy subjects group	Drug: HRS-1780; Single dose in each arm
Experimental: Mild renal impairment group	Drug: HRS-1780; Single dose in each arm
Experimental: Moderate renal impairment group	Drug: HRS-1780; Single dose in each arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics-Cmax	Maximum observed concentration of HRS-1780	Start of Treatment to end of study (approximately 1 week)
Pharmacokinetics-AUC0-last	Area under the concentration-time curve from time 0 to last time point after HRS-1780 administration	Start of Treatment to end of study (approximately 1 week)
Pharmacokinetics-AUC0-inf	Area under the concentration-time curve from time 0 to infinity after HRS-1780 administration	Start of Treatment to end of study (approximately 1 week)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics-Tmax	Time to Cmax of HRS-1780	Start of Treatment to end of study (approximately 1 week)
Pharmacokinetics-t1/2	Terminal elimination half-life of HRS-1780	Start of Treatment to end of study (approximately 1 week）
Pharmacokinetics-CL/F	Apparent clearance of HRS-1780	Start of Treatment to end of study (approximately 1 week)
Pharmacokinetics-Vz/F	Apparent volume of distribution during terminal phase of HRS-1780	Start of Treatment to end of study (approximately 1 week)
Pharmacokinetics-Cumulative excretion (Ae)	Cumulative amount of HRS-1780 excreted in urine	Start of Treatment to end of study (approximately 1 week)
Pharmacokinetics-Cumulative excretion rate (Ae%)	Cumulative percentage of HRS-1780 recovered in urine	Start of Treatment to end of study (approximately 1 week)
Pharmacokinetics-Renal clearance (CLr)	Clearance of HRS-1780 by kidney	Start of Treatment to end of study (approximately 1 week)
Binding rates of plasma protein (BRPP) of HRS-1780	Binding rates of plasma protein	Start of Treatment to end of study (approximately 1 week)
Adverse events	Incidence and severity of adverse events	Start of Treatment to end of study (approximately 1 week)

Collaborators and Investigators

• Sponsor: Shandong Suncadia Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2023
• Primary Completion (Estimated): November 30, 2023
• Study Completion (Estimated): December 8, 2023

Study Registration Dates

• First Submitted: August 7, 2023
• First Submitted That Met QC Criteria: September 14, 2023
• First Posted (Actual): September 15, 2023

Study Record Updates

• Last Update Posted (Actual): September 15, 2023
• Last Update Submitted That Met QC Criteria: September 14, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Renal Insufficiency
• Other Study ID Numbers: HRS-1780-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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