A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HRS3797 in Healthy Subjects

Dose Escalation Study on the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HRS3797 After Intravenous Infusion Administration in Healthy Adults

This is a single-center, open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of HRS3797 in Chinese adults. To evaluate the effect of IV infusion duration on the safety, tolerability, pharmacokinetics and pharmacodynamics of HRS3797. To explore the ED95 dosage of HRS3797 in Chinese adults.

Study Overview

• Status: Completed
• Conditions: Skeletal Muscle Relaxation
• Intervention / Treatment: Drug: HRS3797; Drug: HRS3797; Drug: HRS3797

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410013
      • The Third Xiangya Hospital of Central South University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Healthy male and female subjects aged 18 to 45 years;
2. Conform to the ASA I Physical Status Classification;
3. Male subjects weighed ≥ 50kg, female subjects weighed ≥ 45kg, and body mass index (BMI) was in the range of 19.0~26.0 kg/m2 (inclusive);
4. No pregnancy plan for the next 3 months and voluntary use of highly effective contraception during the trial;
5. Able and willing to provide a written informed consent.

Exclusion Criteria:

1. Subjects with any clinically serious disease, such as circulatory, endocrine, nervous, digestive, respiratory, hematological, immunological, psychiatric, or metabolic abnormalities, that may affect the pharmacokinetic characteristics or safety evaluation of the investigational drug as determined by the investigator;
2. Subjects with neuromuscular disease;
3. Subjects with a history of anatomic airway abnormalities;
4. Subjects with any known allergy history or specific allergic diseases (e.g., allergic asthma, urticaria, eczema, etc.);
5. Subjects who underwent major surgery within 3 months prior to screening;
6. Subjects who underwent surgery that could significantly affect the pharmacokinetic characteristics or safety evaluation of the investigational drug, or who planned to undergo surgery during the study period;
7. Subjects who received antihistamines or antidepressants within 3 months prior to screening;
8. Subjects who used any drug that inhibits or induces liver metabolism of drugs (e.g., inducers - barbiturates, carbamazepine, phenytoin, glucocorticoids, omeprazole; Inhibitors - SSRI antidepressants, cimetidine, diltiazem, macrolides, nitroimidazoles, sedatives and hypnotics, verapamil, fluoroquinolones, antihistamines) within 30 days prior to administration;
9. Subjects who had used any medication within 14 days prior to administration;
10. Subjects who took other investigational drugs or used investigational devices within 3 months prior to the screening, or who planned to participate in other clinical trials during the study period;
11. Subjects who donated blood or suffered massive blood loss of >= 400 mL (except for physiological blood loss in women), received blood transfusions or used blood products within 3 months prior to the study, or planned to donate blood during the study period or within 1 month after finishing the study;
12. Subjects who smoked more than 5 cigarettes per day on average within 3 months prior to the study, or who could not quit smoking during the study period;
13. Subjects had a history of alcohol abuse within 3 months prior to the study, i.e., an average of more than 14 units of alcohol per week;
14. Subjects who consumed excessive amounts of tea, coffee, and caffeinated beverages within 3 months prior to the study;
15. Subjects who consumed special diet (e.g., grapefruit, grapefruit juice or food/drink containing grapefruit juice, chocolate, tobacco, alcohol, caffeine, etc.) within 48 hours before administration;
16. Subjects who have special requirements for diet and cannot comply with a unified diet;
17. The results of various examinations during the screening period were judged by the research doctor to be clinically significant abnormal;
18. Subjects who have one or more positive test results for hepatitis B virus surface antigen, hepatitis C virus antibody, human immunodeficiency virus antibody, and Treponema pallidum antibody;
19. Women who are pregnant or have a positive pregnancy test, or during breast-feeding;
20. Subjects with positive alcohol expiratory test results;
21. Subjects with positive smoking test results;
22. Not suitable to be included in the study for other reasons as considered by investigators.

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

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group A1; HRS3797 for injection	Drug: HRS3797; HRS3797 for injection, low dose; Drug: HRS3797; HRS3797 for injection, medium dose; Drug: HRS3797; HRS3797 for injection, high dose
Experimental: Treatment group A2; HRS3797 for injection	Drug: HRS3797; HRS3797 for injection, low dose; Drug: HRS3797; HRS3797 for injection, medium dose; Drug: HRS3797; HRS3797 for injection, high dose
Experimental: Treatment group B1; HRS3797 for injection	Drug: HRS3797; HRS3797 for injection, low dose; Drug: HRS3797; HRS3797 for injection, medium dose; Drug: HRS3797; HRS3797 for injection, high dose
Experimental: Treatment group B2; HRS3797 for injection	Drug: HRS3797; HRS3797 for injection, low dose; Drug: HRS3797; HRS3797 for injection, medium dose; Drug: HRS3797; HRS3797 for injection, high dose
Experimental: Treatment group C1; HRS3797 for injection	Drug: HRS3797; HRS3797 for injection, low dose; Drug: HRS3797; HRS3797 for injection, medium dose; Drug: HRS3797; HRS3797 for injection, high dose
Experimental: Treatment group C2; HRS3797 for injection	Drug: HRS3797; HRS3797 for injection, low dose; Drug: HRS3797; HRS3797 for injection, medium dose; Drug: HRS3797; HRS3797 for injection, high dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum T1 Suppression	0 minute to full neuromuscular recovery after administration
Time to Maximum T1 Suppression	0 minute to full neuromuscular recovery after administration
The onset of neuromuscular block	0 minute to full neuromuscular recovery after administration
The duration of neuromuscular block	0 minute to full neuromuscular recovery after administration
The recovery rate of neuromuscular block	0 minute to full neuromuscular recovery after administration
Pharmacokinetic parameter of HRS3797: Cmax	0 minute to 1.5 hour after administration
Pharmacokinetic parameter of HRS3797: AUC0-t	0 minute to 1.5 hour after administration
Pharmacokinetic parameter of HRS3797: AUC0-∞	0 minute to 1.5 hour after administration
Pharmacokinetic parameter of HRS3797: Tmax	0 minute to 1.5 hour after administration
Pharmacokinetic parameter of HRS3797: t1/2z	0 minute to 1.5 hour after administration
Pharmacokinetic parameter of HRS3797: CLz	0 minute to 1.5 hour after administration
Pharmacokinetic parameter of HRS3797: Vz	0 minute to 1.5 hour after administration
The change of plasma histamine concentration from baseline	0 minute to 1 hour after administration
The incidence and severity of adverse events/serious adverse events	from ICF signing date to day 28

Secondary Outcome Measures

Outcome Measure	Time Frame
The ED95 dosage	0 minute to full neuromuscular recovery after administration

Collaborators and Investigators

• Sponsor: Fujian Shengdi Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2023
• Primary Completion (Actual): June 2, 2023
• Study Completion (Actual): June 2, 2023

Study Registration Dates

• First Submitted: January 18, 2023
• First Submitted That Met QC Criteria: January 18, 2023
• First Posted (Actual): January 27, 2023

Study Record Updates

• Last Update Posted (Actual): June 7, 2023
• Last Update Submitted That Met QC Criteria: June 5, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: HRS3797-103

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