A Phase I Single- and Multiple- Ascending Dose and Food Effect Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HRS-7535 in Healthy Subjects

A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HRS-7535 in Healthy Subjects

This is a randomized, double-blinded, placebo-controlled study to evaluate the safety, tolerability, Pharmacokinetics and Pharmacodynamics of single ascending dose (Part A) and multiple ascending dose (Part B) of HRS-7535 in healthy subjects.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: Placebo; Drug: HRS-7535

• Study Type: Interventional
• Enrollment (Anticipated): 106
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yimei Xu; Phone Number: 0518-82342973; Email: yimei.xu@hengrui.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Must be 18 to 55 years of age (inclusive) healthy male or female of nonchildbearing potential;
2. Body weight of at least 50 kg for male, and 45 kg for female; and Body Mass Index (BMI) within the range of 19 to 28 kg/m2 (inclusive);
3. Subjects (including partners) of childbearing potential are willing to use protocol specified effective methods of contraception from screening to at least 6 months after the final dose of study drug;
4. Able and willing to provide written informed consent and to comply with the study protocol;
5. Physical examination, vital signs are normal or are judged not clinically significant by the investigator;

Exclusion Criteria:

1. Participants with any abnormal results and judged clinically significant by the investigator;
2. HbA1c ≥6.2%, fasting blood-glucose ≤3.9mmol/L (70mg/dL) or ≥6.1mmol/L(110mg/dL) at screening ;
3. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2 x ULN; total bilirubin ≥1.5 x ULN at screening;
4. Abnormal ECG that is clinically significant, or QTcF >450 msec;
5. Positive test result of any of the following at screening: hepatitis B surface antigen (HBsAg), hepatitis C antibody, syphilis, or human immunodeficiency virus (HIV) antibody;
6. Any malignancy (except basal cell carcinoma and squamous cell carcinoma of the skin) in the previous 5 years;
7. Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, history of pancreatitis or symptomatic gallbladder disease;
8. History of gastric emptying anomalies (gastric outlet obstruction), severe chronic gastrointestinal diseases (such as inflammatory bowel disease, active ulcer) ;
9. Subject with major medical history of heart, liver, kidney, endocrine, digestive, blood, respiratory and genitourinary system or existing diseases of the above systems;
10. Use any prescription drugs, non-prescription drugs, food supplements, vitamins and Chinese herbal medicines within 2 weeks before administration;
11. Subject who received bariatric surgery or procedures, or use of weight-reducing drugs within 3 months prior to administration, or body weight change of more than ±10% within 3 months prior to administration;
12. Use any drugs that may affect glucose metabolism were used within 1 month before administration.
13. Suspected allergy to any ingredient in the study drug;
14. Participation in clinical trials of any drug or medical device within 3 months before screening;
15. History of regular alcohol consumption exceeding 14 drinks per week within 6 months before screening;
16. More than 5 cigarettes per day or cigarettes within 3 months before screening;
17. Subjects who consume alcoholic beverages, Seville oranges, grapefruit or juices, or products containing caffeine or xanthine (such as coffee, tea, cola drinks and chocolate) from 2 days before the start of study treatment;
18. Strenuous exercise in 48 hours before treatment;
19. Subjects with a history of drug abuse, drug dependence, or a positive drugs of abuse test, or a positive alcohol breath test before study drug administration;
20. Donation or loss of blood of ≥ 200 mL within 1 month or of ≥ 400 mL within 3 months prior to the first dose of study drug;
21. Subjects can't tolerate venipuncture;
22. Subjects have special dietary requirements and cannot comply with the unified diet;
23. Other conditions judged by the investigator to be not suitable to participate in the trial;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group A; Drug: HRS-7535	Drug: HRS-7535; Drug: HRS-7535
PLACEBO_COMPARATOR: Group B; Drug: Placebo	Drug: Placebo; Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adverse Events	Number of adverse events per subject, including clinically relevant changes in physical examination, vital signs, laboratory tests and ECGs;	Day-2 to last follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) profile of HRS-7535 - AUC0-t	Area under the concentration-time curve from time zero to the last quantifiable time point t (AUC0-t);	pre-dose to 96 hours post-dose
Pharmacokinetic (PK) profile of HRS-7535 - AUC0-∞	Area under the plasma concentration-time curve from time zero to infinity (AUC0-∞);	pre-dose to 96 hours post-dose
Pharmacokinetic (PK) profile of HRS-7535 - Cmax	Maximum observed concentration (Cmax);	pre-dose to 96 hours post-dose
Pharmacokinetic (PK) profile of HRS-7535 - Tmax	Time to maximum observed concentration (Tmax);	pre-dose to 96 hours post-dose
Pharmacokinetic (PK) profile of HRS-7535 - t1/2	Terminal elimination half-life (t1/2)	pre-dose to 96 hours post-dose
Pharmacokinetic (PK) profile of HRS-7535 - CL/F	Apparent clearance (CL/F);	pre-dose to 96 hours post-dose
Pharmacokinetic (PK) profile of HRS-7535 - Vz/F	Apparent volume of distribution (Vz/F);	pre-dose to 96 hours post-dose
Pharmacokinetic (PK) profile of HRS-7535 - AUC0-τ,ss	Area under the plasma concentration-time curve from time zero to tau at steady state (AUC0-τ,ss)	pre-last dose to 96 hours post- last dose
Pharmacokinetic (PK) profile of HRS-7535 - AUC0-t,ss	AUC0-t at steady state (AUC0-t,ss)	pre- last dose to 96 hours post- last dose
Pharmacokinetic (PK) profile of HRS-7535 - AUC0-∞,ss	AUC0-∞ at steady state (AUC0-∞,ss)	pre- last dose to 96 hours post- last dose
Pharmacokinetic (PK) profile of HRS-7535 - Tmax,ss	Tmax at steady state (Tmax,ss)	pre- last dose to 96 hours post- last dose
Pharmacokinetic (PK) profile of HRS-7535 - Cmax,ss	Cmax at steady state (Cmax,ss)	pre- last doseto 96 hours post- last dose
Pharmacokinetic (PK) profile of HRS-7535 - Ctrough,ss	Ctrough at steady state (Ctrough,ss)	pre- last dose to 96 hours post- last dose
Pharmacokinetic (PK) profile of HRS-7535 - Cavg,ss	Cavg at steady state (Cavg,ss)	pre- last dose to 96 hours post- last dose
Pharmacokinetic (PK) profile of HRS-7535 - DF	Degree of fluctuation at steady state (DF)	pre- last dose to 96 hours post- last dose
Pharmacokinetic (PK) profile of HRS-7535 - Vz,ss/F	Vz/F at steady state (Vz,ss/F)	pre- last dose to 96 hours post- last dose
Pharmacokinetic (PK) profile of HRS-7535 - CLss/F	CL/F at steady state (CLss/F)	pre- last dose to 96 hours post- last dose
Pharmacokinetic (PK) profile of HRS-7535 - t1/2,ss	t1/2 at steady state (t1/2,ss)	pre- last dose to 96 hours post- last dose
Pharmacodynamic (PD) profile of doses of HRS-7535 - blood glucose		pre-dose to 24 hours post-dose
Pharmacodynamic (PD) profile of doses of HRS-7535 - insulin		pre-dose to 24 hours post-dose
Pharmacodynamic (PD) profile of doses of HRS-7535 - C-peptide		pre-dose to 24 hours post-dose
Pharmacodynamic (PD) profile of doses of HRS-7535 - glucagon		pre-dose to 24 hours post-dose
Pharmacodynamic (PD) profile of doses of HRS-7535 - fructosamine		pre-dose up to 96 hours after the last dose
PD profile of multiple doses of HRS-7535 - HbA1c		pre-dose up to 96 hours after the last dose
PD profile of multiple doses of HRS-7535 - 5-points glucose profile		pre-dose up to 24 hours after the last dose
PD profile of multiple doses of HRS-7535 - weight		pre-dose up to 96 hours after the last dose

Collaborators and Investigators

• Sponsor: Shandong Suncadia Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): May 1, 2022
• Primary Completion (ANTICIPATED): September 18, 2022
• Study Completion (ANTICIPATED): March 15, 2023

Study Registration Dates

• First Submitted: April 20, 2022
• First Submitted That Met QC Criteria: April 20, 2022
• First Posted (ACTUAL): April 26, 2022

Study Record Updates

• Last Update Posted (ACTUAL): April 26, 2022
• Last Update Submitted That Met QC Criteria: April 20, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: HRS-7535-101

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