A Study of HS-10501 Tablets in Healthy Subjects

A Randomized, Double-blind, Placebo-controlled, Dose Escalation Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of HS-10501 Tablets After Single and Multiple Oral Doses in Healthy Subjects

The purpose of this study is to evaluate the safety, tolerability, Pharmacokinetics and Pharmacodynamics of single dose and multiple dose of HS-10501 tables in healthy subjects. This is the first clinical study of HS-10501 tables. This study has 2 parts. Parts A involve a single dose of HS-10501 tables or placebo and will last about 8 days. Also, this part will also further explore the food effect. Parts B involve multiple doses of HS-10501 tables or placebo and will last about 4 weeks.

Study Overview

• Status: Recruiting
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: Placebo; Drug: HS-10501 tablet

• Study Type: Interventional
• Enrollment (Estimated): 84
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Wei Hu, MD; Phone Number: (+86)13856086475; Email: ayefygcp@163.com
• Study Contact Backup: Name: Yijun Du, MD; Phone Number: (+86)13866700016; Email: 2460679232@qq.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230601
      • Recruiting
      • The Second Hospital of Anhui University
      • Contact: Wei Hu, MD; Phone Number: 13856086475; Email: ayefygcp@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Able and willing to provide written informed consent and to comply with the study protocol;
2. Must be 18 to 55 years of age (inclusive) healthy male or female;
3. Body weight of at least 50.0 kg for male, and 45.0 kg for female; and Body Mass Index (BMI) within the range of 19.0 to 28.0 kg/m2 (inclusive);
4. Subjects (including partners) of childbearing potential are willing to use protocol specified effective methods of contraception from the date of signing the informed consent form to 30 days after the last dose;
5. Female subjects must have a negative blood pregnancy test report 3 days before dosing.

Exclusion Criteria:

1. Pregnant or lactating women;
2. Subjects with a history of cardiovascular, respiratory, liver, kidney, digestive tract, mental, neurological, hematological, immune, and metabolic abnormalities and other diseases, and not suitable for the study as assessed by the investigator;
3. Subjects with clinically significant abnormalities in vital signs, physical examination, laboratory tests, or 12-lead ECG during the screening period;
4. Have received major surgery within 3 months before screening or have surgery plan during the study;
5. History of severe infection within 30 days before screening or currently experiencing severe infection;
6. The alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) are higher than the upper limit of normal (ULN);
7. Positive for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV-Ab), HIV antibody (HIV-Ab), or treponema pallidum antibody (TP-Ab);
8. Glycosylated hemoglobin (HbA1c) ≥ 6.0% and fasting blood glucose ≤ 3.9 mmol/L (70 mg/dL) or ≥ 6.1 mmol/L (110 mg/dL) at screening;
9. History of drug abuse and use of hard drugs within 1 year before the study or positive for urine drug screening;
10. Addicted to smoking or smokers who smoke 5 or more cigarettes per day on average within 3 months before screening;
11. History of alcohol abuse, or a single consumption of more than 14 units of alcohol in the past two weeks, or positive for breath alcohol test at screening;
12. Participating in any clinical trial involving drugs or medical devices within 3 months before screening;
13. Blood donation or loss of ≥ 400 mL or blood transfusion within 3 months before screening; blood donation or loss of ≥ 200 mL within 1 month before screening;
14. Subjects with severe allergic disease, or suspected allergy to any ingredient in the study drugs, or allergic constitution;
15. Subjects with concomitant diseases that may significantly affect the absorption of drugs or nutrients as judged by the investigator;
16. Subjects with a history of pancreatitis, and serum amylase or lipase greater than the ULN;
17. History or family history of medullary thyroid cancer and multiple endocrine neoplasia syndrome type 2;
18. Diet or weight loss treatment within 3 months prior to administration or having weight change of more than 5% or significant change in living habits;
19. Any medication taken within 2 weeks or 5 half-lives (whichever is longer) before screening and any medication expected to be taken throughout the study;
20. Any physiological or psychological diseases or conditions that may increase the risk of the study, affect the subject's compliance with the protocol, or affect the subject's completion of the study, as judged by the investigator;
21. Those who should not be enrolled per the investigator's opinion.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Single dose of HS-10501 administered orally under fasted conditions	Drug: Placebo; Administered orally; Drug: HS-10501 tablet; Administered orally
Experimental: Cohort 2; Single dose of HS-10501 administered orally under fasted conditions	Drug: Placebo; Administered orally; Drug: HS-10501 tablet; Administered orally
Experimental: Cohort 3; Single dose of HS-10501 administered orally under fed and fasted conditions	Drug: Placebo; Administered orally; Drug: HS-10501 tablet; Administered orally
Experimental: Cohort 4; Single dose of HS-10501 administered orally under fasted conditions	Drug: Placebo; Administered orally; Drug: HS-10501 tablet; Administered orally
Experimental: Cohort 5; Single dose of HS-10501 administered orally under fasted conditions	Drug: Placebo; Administered orally; Drug: HS-10501 tablet; Administered orally
Experimental: Cohort 6; Single dose of HS-10501 administered orally under fasted conditions	Drug: Placebo; Administered orally; Drug: HS-10501 tablet; Administered orally
Experimental: Cohort 7; Drugs are given twice a day (BID) for 27 days, and only one morning dose is given on the 28th day.	Drug: Placebo; Administered orally; Drug: HS-10501 tablet; Administered orally
Experimental: Cohort 8; Drugs are given once a day (QD) for 28 days.	Drug: Placebo; Administered orally; Drug: HS-10501 tablet; Administered orally
Experimental: Cohort 9; Drugs are given twice a day (BID) for 27 days, and only one morning dose is given on the 28th day.	Drug: Placebo; Administered orally; Drug: HS-10501 tablet; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of adverse events(AE) , serious AEs and AE leading to withdrawal from treatment.	An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A serious AE (SAE) is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or is a congenital anomaly/birth defect.	Day1 to last follow-up, SAD: Baseline to Day 8; MAD: Baseline to Day 35.
Number of participants with clinically significant abnormalities in lab tests	Laboratory tests include blood routine, urine routine, blood biochemistry and coagulation function, etc.	Day1 to last follow-up, SAD: Baseline to Day 8; MAD: Baseline to Day 35.
Number of participants with clinically significant change from baseline in vital signs		Day1 to last follow-up, SAD: Baseline to Day 8; MAD: Baseline to Day 35.
Change from baseline in Electrocardiogram (ECG)	ECG parameters including heart rate, PR interval, QRS interval and QTcF, etc.	Day1 to last follow-up, SAD: Baseline to Day 8; MAD: Baseline to Day 35.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) profile of HS-10501 - AUC0-t	Area under the concentration-time curve from time zero to the last quantifiable time point t (AUC0-t)	pre-dose to 72 hours post-dose
Pharmacokinetic (PK) profile of HS-10501 - AUC0-∞	Area under the plasma concentration-time curve from time zero to infinity (AUC0-∞);	pre-dose to 72 hours post-dose
Pharmacokinetic (PK) profile of HS-10501 - Cmax	Maximum observed concentration (Cmax)	pre-dose to 72 hours post-dose
Pharmacokinetic (PK) profile of HS-10501 - Tmax	Time to maximum observed concentration (Tmax)	pre-dose to 72 hours post-dose
Pharmacokinetic (PK) profile of HS-10501 - t1/2	Terminal elimination half-life (t1/2)	pre-dose to 72 hours post-dose
Pharmacokinetic (PK) profile of HS-10501 - CL/F	Apparent clearance (CL/F)	pre-dose to 72 hours post-dose
Pharmacokinetic (PK) profile of HS-10501- Vz/F	Apparent volume of distribution (Vz/F)	pre-dose to 72 hours post-dose
Pharmacokinetic (PK) profile of HS-10501-λz	elimination rate constant (λz)	pre-dose to 72 hours post-dose
Pharmacokinetic (PK) profile of HS-10501- AUC0-τ	area under plasma concentration-time curve within a dosing interval	pre-dose to 72 hours post-dose
Pharmacodynamic (PD) profile of doses of HS-10501 - AUC0-t of blood glucose-time curve after oral glucose tolerance test (OGTT)	Area under the glucose-time curve from time zero to the last quantifiable time point t (AUC0-t) after oral glucose tolerance test (OGTT)	before to 3 hours after the first intake of glucose on Day-1，Day 1 and Day 28
Pharmacodynamic (PD) profile of doses of HS-10501 - AUC0-t of blood insulin-time curve after oral glucose tolerance test (OGTT)	Area under the insulin-time curve from time zero to the last quantifiable time point t (AUC0-t) after oral glucose tolerance test (OGTT)	before to 3 hours after the first intake of glucose on Day-1，Day 1 and Day 28
body weight changes	Change in body weight from baseline after treatment	from day-1to day 28

Collaborators and Investigators

• Sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2024
• Primary Completion (Estimated): January 31, 2025
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: March 21, 2024
• First Submitted That Met QC Criteria: April 7, 2024
• First Posted (Actual): April 11, 2024

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 7, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: HS-10501-101

Drug and device information, study documents

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