Safety and Tolerance of Increased Doses of HRS-1780 Tablets in Healthy Subjects

A Phase I Single and Multiple Ascending Dose and Food Effect Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of HRS-1780 Tablets in Healthy Male Subjects

This is a randomized, double-blind, placebo-controlled phase I clinical study. The primary objective is to evaluate the safety, tolerability, PK, and PD of single- and multiple-dose HRS-1780 in healthy subjects, and to evaluate the food effect on PK of HRS-1780.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Drug: HRS-1780 table or placebo; Drug: HRS-1780 table or placebo; Drug: HRS-1780 table or placebo

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Manchen Bao, M.D; Phone Number: 0518-82342973; Email: manchen.bao@hengrui.com

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610044
      • West China Hospital of Sichuan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. 18-45 years old (including boundary value, whichever is at the time of signing the informed consent form), healthy male.
2. Weight ≥50 kg, body mass index (BMI = body mass/height square (kg/m2)) is in the range of 18-28 (including boundary values)
3. Obtain informed consent before any activity related to the experiment begins, have a full understanding of the purpose and significance of the experiment, and be willing to comply with the test plan and dietary requirements.
4. Subjects (including partners) have no family planning within 3 months from the beginning of the signing of the informed consent form to the last dose, and are willing to adopt the efficient contraceptive measures stipulated in the program and guarantee not to donate sperm.

Exclusion Criteria:

1. People with a history of hypertension.
2. People with severe systemic infectious diseases, serious trauma or major surgical surgery before screening; those who plan to undergo surgery during the trial
3. There has been a history of clinical abnormal gastric emptying and severe chronic gastrointestinal diseases.
4. Diseases found to show clinical significance before screening
5. Combined with diuretics before screening
6. Drugs were used 2 weeks before screening.
7. Laboratory or physical examination with any abnormalities and the researcher's judgment is clinically significant.
8. 12-lead electrocardiogram is abnormal and of clinical significance
9. Positive for hepatitis B surface antigen, positive for hepatitis C antibody, positive for syphilis spirochete antibody, positive for HIV antibody
10. People with severe allergic diseases or known or suspected of being allergic to any of the ingredients in the research drug, allergic constitution (multiple drugs and food allergies)
11. Participated in the clinical trial of any drug or medical device within the first 3 months of screening or planned to participate in the clinical trial of other drugs or medical devices during the trial period (subject to the signing of informed consent)
12. Drink more than 14 units of alcohol per week in the first 6 months of screening; or those who have taken alcohol products 48 hours before administration; or those who have tested positive for alcohol exhalation during the baseline period.
13. Smoking more than 5 cigarettes a day in the 3 months before screening or using any tobacco products 48 h before administration.
14. Drink/eat coffee, tea, grapefruit, chocolate or soft drinks, such as cola containing methamphetrine (tein, caffeine or cocoaine) within 3 days before screening
15. Those who have had a history of drug abuse in the past five years or have used drugs in the first three months of the trial; or urine drugs are screened positive
16. Blood donation ≥ 200 mL within 1 month before screening; or blood donation ≥ 400 mL within 3 months before screening; or trauma or surgical surgery with blood donation (plasma or platelets) or blood loss of ≥ 400 mL within 2 weeks
17. Inability tolerate venous puncture and blood collection or dizziness
18. Subjects who believe that there are other factors that are not suitable to participate in this test

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1; HRS-1780 table or placebo single dose	Drug: HRS-1780 table or placebo; HRS-1780 table or placebo single dose; Drug: HRS-1780 table or placebo; HRS-1780 table or placebo single dose with food effect; Drug: HRS-1780 table or placebo; HRS-1780 table or placebo multiple dose
Experimental: Part 2; HRS-1780 table or placebo single dose with food effect	Drug: HRS-1780 table or placebo; HRS-1780 table or placebo single dose; Drug: HRS-1780 table or placebo; HRS-1780 table or placebo single dose with food effect; Drug: HRS-1780 table or placebo; HRS-1780 table or placebo multiple dose
Experimental: Part 3; HRS-1780 table or placebo multiple dose	Drug: HRS-1780 table or placebo; HRS-1780 table or placebo single dose; Drug: HRS-1780 table or placebo; HRS-1780 table or placebo single dose with food effect; Drug: HRS-1780 table or placebo; HRS-1780 table or placebo multiple dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Assess the incidence and severity of adverse events in healthy subjects after single and multiple doses of HRS-1780 tablets	About a month from the first medication to the evaluation.

Secondary Outcome Measures

Outcome Measure	Time Frame
Assess the concentration of HRS-1780 in plasma and urine	About 4 weeks after the first dose
Evaluation of AUC0-t of HRS-1780 in plasma and urine	About 4 weeks after the first dose
Evaluation of AUC0-∞ of HRS-1780 in plasma and urine	About 4 weeks after the first dose
Evaluation of Tmax of HRS-1780 in plasma and urine	About 4 weeks after the first dose
Evaluation of Cmax of HRS-1780 in plasma and urine	About 4 weeks after the first dose
Evaluation of t1/2 of HRS-1780 in plasma and urine	About 4 weeks after the first dose
Evaluate the blood pressure of subjects over time after HRS-1780 administration	About 4 weeks after the first dose
Evaluate the heart rate of subjects over time after HRS-1780 administration	About 4 weeks after the first dose
Evaluate the concentrations of plasma renin activity of subjects over time after HRS-1780 administration	About 4 weeks after the first dose
Evaluate the plasma aldosterone of subjects over time after HRS-1780 administration	About 4 weeks after the first dose
Evaluate the plasma angiotensin II of subjects over time after HRS-1780 administration	About 4 weeks after the first dose
Evaluate the urinary creatinine curve of subjects with time after HRS-1780 administration	About 4 weeks after the first dose
Evaluate the change curve of urine creatinine over time relative to baseline in subjects after HRS-1780 administration	About 4 weeks after the first dose

Collaborators and Investigators

• Sponsor: Shandong Suncadia Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2023
• Primary Completion (Estimated): December 1, 2023
• Study Completion (Estimated): December 1, 2023

Study Registration Dates

• First Submitted: November 24, 2022
• First Submitted That Met QC Criteria: December 5, 2022
• First Posted (Actual): December 6, 2022

Study Record Updates

• Last Update Posted (Actual): October 25, 2023
• Last Update Submitted That Met QC Criteria: October 23, 2023
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: HRS-1780-101

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
• product manufactured in and exported from the U.S.: No