Healthy Subjects
Conditions
Brief summary
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.
Interventions
DRUGHRS-7535
Drug: HRS-7535
DRUGPlacebo
Drug: Placebo
Sponsors
Shandong Suncadia Medicine Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
HRS-7535 tablet compared with placebo
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of adverse Events | Day-2 to last follow-up | Number of adverse events per subject, including clinically relevant changes in physical examination, vital signs, laboratory tests and ECGs; |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) profile of HRS-7535 - AUC0-∞ | pre-dose to 96 hours post-dose | Area under the plasma concentration-time curve from time zero to infinity (AUC0-∞); |
| Pharmacokinetic (PK) profile of HRS-7535 - Cmax | pre-dose to 96 hours post-dose | Maximum observed concentration (Cmax); |
| Pharmacokinetic (PK) profile of HRS-7535 - Tmax | pre-dose to 96 hours post-dose | Time to maximum observed concentration (Tmax); |
| Pharmacokinetic (PK) profile of HRS-7535 - t1/2 | pre-dose to 96 hours post-dose | Terminal elimination half-life (t1/2) |
| Pharmacokinetic (PK) profile of HRS-7535 - CL/F | pre-dose to 96 hours post-dose | Apparent clearance (CL/F); |
| Pharmacokinetic (PK) profile of HRS-7535 - Vz/F | pre-dose to 96 hours post-dose | Apparent volume of distribution (Vz/F); |
| Pharmacokinetic (PK) profile of HRS-7535 - AUC0-τ,ss | pre-last dose to 96 hours post- last dose | Area under the plasma concentration-time curve from time zero to tau at steady state (AUC0-τ,ss) |
| Pharmacokinetic (PK) profile of HRS-7535 - AUC0-t,ss | pre- last dose to 96 hours post- last dose | AUC0-t at steady state (AUC0-t,ss) |
| Pharmacokinetic (PK) profile of HRS-7535 - AUC0-∞,ss | pre- last dose to 96 hours post- last dose | AUC0-∞ at steady state (AUC0-∞,ss) |
| Pharmacokinetic (PK) profile of HRS-7535 - Tmax,ss | pre- last dose to 96 hours post- last dose | Tmax at steady state (Tmax,ss) |
| Pharmacokinetic (PK) profile of HRS-7535 - Cmax,ss | pre- last doseto 96 hours post- last dose | Cmax at steady state (Cmax,ss) |
| Pharmacokinetic (PK) profile of HRS-7535 - Ctrough,ss | pre- last dose to 96 hours post- last dose | Ctrough at steady state (Ctrough,ss) |
| Pharmacokinetic (PK) profile of HRS-7535 - AUC0-t | pre-dose to 96 hours post-dose | Area under the concentration-time curve from time zero to the last quantifiable time point t (AUC0-t); |
| Pharmacokinetic (PK) profile of HRS-7535 - DF | pre- last dose to 96 hours post- last dose | Degree of fluctuation at steady state (DF) |
| Pharmacokinetic (PK) profile of HRS-7535 - Vz,ss/F | pre- last dose to 96 hours post- last dose | Vz/F at steady state (Vz,ss/F) |
| Pharmacokinetic (PK) profile of HRS-7535 - CLss/F | pre- last dose to 96 hours post- last dose | CL/F at steady state (CLss/F) |
| Pharmacokinetic (PK) profile of HRS-7535 - t1/2,ss | pre- last dose to 96 hours post- last dose | t1/2 at steady state (t1/2,ss) |
| 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 | — |
| Pharmacokinetic (PK) profile of HRS-7535 - Cavg,ss | pre- last dose to 96 hours post- last dose | Cavg at steady state (Cavg,ss) |
Contacts
Primary ContactYimei Xu
Backup ContactShujin Cheng
Outcome results
None listed