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
Overview
- Phase
- Phase 1
- Intervention
- HS-10501 tablet
- Conditions
- Healthy Subjects
- Sponsor
- Jiangsu Hansoh Pharmaceutical Co., Ltd.
- Enrollment
- 84
- Locations
- 1
- Primary Endpoint
- Number of participants with clinically significant change from baseline in vital signs
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Able and willing to provide written informed consent and to comply with the study protocol;
- •Must be 18 to 55 years of age (inclusive) healthy male or female;
- •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);
- •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;
- •Female subjects must have a negative blood pregnancy test report 3 days before dosing.
Exclusion Criteria
- •Pregnant or lactating women;
- •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;
- •Subjects with clinically significant abnormalities in vital signs, physical examination, laboratory tests, or 12-lead ECG during the screening period;
- •Have received major surgery within 3 months before screening or have surgery plan during the study;
- •History of severe infection within 30 days before screening or currently experiencing severe infection;
- •The alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) are higher than the upper limit of normal (ULN);
- •Positive for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV-Ab), HIV antibody (HIV-Ab), or treponema pallidum antibody (TP-Ab);
- •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;
- •History of drug abuse and use of hard drugs within 1 year before the study or positive for urine drug screening;
- •Addicted to smoking or smokers who smoke 5 or more cigarettes per day on average within 3 months before screening;
Arms & Interventions
Cohort 1
Single dose of HS-10501 administered orally under fasted conditions
Intervention: HS-10501 tablet
Cohort 1
Single dose of HS-10501 administered orally under fasted conditions
Intervention: Placebo
Cohort 2
Single dose of HS-10501 administered orally under fasted conditions
Intervention: HS-10501 tablet
Cohort 2
Single dose of HS-10501 administered orally under fasted conditions
Intervention: Placebo
Cohort 3
Single dose of HS-10501 administered orally under fed and fasted conditions
Intervention: HS-10501 tablet
Cohort 3
Single dose of HS-10501 administered orally under fed and fasted conditions
Intervention: Placebo
Cohort 4
Single dose of HS-10501 administered orally under fasted conditions
Intervention: HS-10501 tablet
Cohort 4
Single dose of HS-10501 administered orally under fasted conditions
Intervention: Placebo
Cohort 5
Single dose of HS-10501 administered orally under fasted conditions
Intervention: HS-10501 tablet
Cohort 5
Single dose of HS-10501 administered orally under fasted conditions
Intervention: Placebo
Cohort 6
Single dose of HS-10501 administered orally under fasted conditions
Intervention: HS-10501 tablet
Cohort 6
Single dose of HS-10501 administered orally under fasted conditions
Intervention: Placebo
Cohort 7
Drugs are given twice a day (BID) for 27 days, and only one morning dose is given on the 28th day.
Intervention: HS-10501 tablet
Cohort 7
Drugs are given twice a day (BID) for 27 days, and only one morning dose is given on the 28th day.
Intervention: Placebo
Cohort 8
Drugs are given once a day (QD) for 28 days.
Intervention: HS-10501 tablet
Cohort 8
Drugs are given once a day (QD) for 28 days.
Intervention: Placebo
Cohort 9
Drugs are given twice a day (BID) for 27 days, and only one morning dose is given on the 28th day.
Intervention: HS-10501 tablet
Cohort 9
Drugs are given twice a day (BID) for 27 days, and only one morning dose is given on the 28th day.
Intervention: Placebo
Outcomes
Primary Outcomes
Number of participants with clinically significant change from baseline in vital signs
Time Frame: Day1 to last follow-up, SAD: Baseline to Day 8; MAD: Baseline to Day 35.
Change from baseline in Electrocardiogram (ECG)
Time Frame: Day1 to last follow-up, SAD: Baseline to Day 8; MAD: Baseline to Day 35.
ECG parameters including heart rate, PR interval, QRS interval and QTcF, etc.
Incidence and severity of adverse events(AE) , serious AEs and AE leading to withdrawal from treatment.
Time Frame: Day1 to last follow-up, SAD: Baseline to Day 8; MAD: Baseline to Day 35.
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.
Number of participants with clinically significant abnormalities in lab tests
Time Frame: Day1 to last follow-up, SAD: Baseline to Day 8; MAD: Baseline to Day 35.
Laboratory tests include blood routine, urine routine, blood biochemistry and coagulation function, etc.
Secondary Outcomes
- Pharmacokinetic (PK) profile of HS-10501 - AUC0-∞(pre-dose to 72 hours post-dose)
- Pharmacokinetic (PK) profile of HS-10501 - Cmax(pre-dose to 72 hours post-dose)
- Pharmacokinetic (PK) profile of HS-10501 - CL/F(pre-dose to 72 hours post-dose)
- Pharmacokinetic (PK) profile of HS-10501- AUC0-τ(pre-dose to 72 hours post-dose)
- Pharmacokinetic (PK) profile of HS-10501 - AUC0-t(pre-dose to 72 hours post-dose)
- Pharmacokinetic (PK) profile of HS-10501 - t1/2(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)(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)(before to 3 hours after the first intake of glucose on Day-1，Day 1 and Day 28)
- Pharmacokinetic (PK) profile of HS-10501 - Tmax(pre-dose to 72 hours post-dose)
- Pharmacokinetic (PK) profile of HS-10501-λz(pre-dose to 72 hours post-dose)
- Pharmacokinetic (PK) profile of HS-10501- Vz/F(pre-dose to 72 hours post-dose)
- body weight changes(from day-1to day 28)