A Phase 1 Study of GZC8072 Tablets Following a Single Dose in Healthy Study Participants and Multiple Doses in Obese/Overweight Study Participants

A Phase 1 Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetic Profile of Single Doses of GZC8072 Tablets in Healthy Adult Participants and to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Profile of Multiple Doses in Participants With Overweight or Obesity

This trial is conducted in China. This study plans to include 2 parts, i.e., a single-dose study and a multiple-dose study:

The single-dose study will be conducted in healthy adult participants to evaluate the safety, tolerability, and pharmacokinetic profile of single doses of GZC8072 Tablets; The multiple-dose study will be conducted in obese or overweight study participants to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic profiles of multiple doses of GZC8072 Tablets.

Inclusion Criteria:

SAD：

1. Provide written informed consent, fully understand the purpose and stipulated procedures of this study, and be willing to participate.
2. Male or female, aged 18-55 years (inclusive) at the time of signing the ICF.
3. Body mass index (BMI) at screening is 19.0-28.0 kg/m² (inclusive); and weight is ≥ 54.0 kg for males and ≥ 50.0 kg for females.
4. Participants must agree to take reliable contraceptive measures for themselves and their partners during the study and within 3 months after administration, and not donate sperm or eggs (egg cells, oocytes) for assisted reproductive purposes.

MAD:

1. Provide written informed consent, fully understand the purpose and stipulated procedures of this study, and be willing to participate.
2. Male or female, aged 18-55 years (inclusive) at the time of signing the ICF.
3. At screening, the body mass index (BMI) is 24 kg/m2 to 35 kg/m2 (inclusive).
4. Participants must agree to take reliable contraceptive measures for themselves and their partners during the study and within 3 months after the last dose, and not donate sperm or eggs (egg cells, oocytes) for assisted reproductive purposes.

Exclusion Criteria:

SAD:

1. History of allergic diathesis, or allergic diseases such as bronchial asthma, urticaria, or eczema (except for mild seasonal allergies) prior to screening, or known or suspected allergy, intolerance, or hypersensitivity to GLP-1RA drugs, SNAC, C10 or other excipients of the investigational medicinal product (IMP) at screening.

2. Participants with a previous or existing history of cardiovascular system, digestive system, respiratory system, urinary system, blood system, nervous system, psychiatric disorders, endocrine diseases (except obesity or overweight), malignant tumors and other diseases that are judged by the investigator to have an impact on the evaluation of the results of this study.

3. Hemorrhage tendency (including but not limited to non-traumatic hemorrhage) within 6 months before screening, or presence of diseases with increased hemorrhage tendency that are clearly diagnosed.

4. History of hypoglycemia (including symptomatic hypoglycemia) within 3 months prior to screening.

5. History of acute or chronic pancreatitis, symptomatic gallbladder disease, pancreatic surgery or trauma before screening; high-risk cholelithiasis (such as sand-like stones, gallbladder and bile duct stones ≤ 5 mm in diameter) during screening; newly diagnosed cholecystitis at screening.

6. Presence of reflux esophagitis at screening, functional dyspepsia, constipation, irritable bowel syndrome, intestinal obstruction, abnormal gastric emptying (e.g., pyloric obstruction), or active peptic ulcer.

7. History or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 prior to screening, or presence of suspected and/or diagnosed malignancy at screening, or history of malignancy prior to screening.

8. Participants who have any clinically significant abnormalities in 12-lead ECG, vital signs (blood pressure, respiration, pulse and body temperature), physical examinations, imaging procedures or laboratory tests (hematology, urinalysis, blood biochemistry and coagulation) at screening or predose as judged by the investigator to be unsuitable for participation in this study, or whose laboratory test items at screening or predose meet any of the following criteria:

   1. eGFR < 90 mL/min/1.73 m2 (eGFR should be estimated using the CKD-EPI formula);
   2. Abnormal fasting plasma glucose (FPG) (FPG ≥ 6.1 mmol/L, or < 3.9 mmol/L);
   3. Hemoglobin A1c (HbA1c) ≥ 6.5%;
   4. Calcitonin ≥ 20 pg/mL;
   5. Those who are positive for four tests for infectious diseases.

9. Major surgery within 6 months prior to screening, or scheduled surgery or hospitalization during the study.

10. Participants who have received any vaccine within 1 month before screening, or plan to receive any vaccine during the study.

11. Use of prescription or over-the-counter drugs, herbal medicines, traditional Chinese medicines, local traditional medicines, vitamins, minerals, or oral iron supplements within 2 weeks prior to IMP administration, or consumption of any food or beverage containing caffeine, xanthine, or potentially affecting study results (e.g., coffee, tea, cola, grapefruit or pomelo juice, dragon fruit, mango), or inability to comply with the above dietary restrictions during the study.

12. Participation in other interventional clinical trials before screening (within the past 3 months or within 5 half-lives after administration of the investigational drug, whichever is longer). Or plan to participate in another clinical study of an IMP, surgery, or device before completing all scheduled assessments in the clinical study.

13. Those who have donated blood or blood products (> 100 mL) or lost a large volume of blood (> 400 mL) within 2 months prior to screening or have planned to donate blood or blood products during the study.

14. History of drug abuse prior to screening; or positive results for drug abuse on D-1.

15. Hisory of alcohol abuse within 3 months prior to screening, defined as an average intake of more than 14 units per week (1 standard unit = 360 mL of beer or 150 mL of 12% wine or 45 mL of 40% spirits); or use of any alcohol-containing products 48 hours before dosing and throughout the study; or abnormal results for breath alcohol test on D-1.

16. Female participants who are pregnant or lactating, or have a positive human chorionic gonadotropin (β-HCG) pregnancy test at screening.

17. Participants who are allergic to any food or have specific dietary requirements and cannot adhere to a standardized diet.

18. Unwillingness to undergo repeated venipuncture due to poor tolerance or difficult venous access, or participant experiences needle or blood phobia.

19. Any condition that, in the investigator's opinion, renders the participant unsuitable for participation in this study, including potential compromise of the participant's rights.

MAD:

1. History of allergic diathesis, or allergic diseases such as bronchial asthma, urticaria, or eczema (except for mild seasonal allergies) prior to screening, or known or suspected allergy, intolerance, or hypersensitivity to GLP-1RA drugs, SNAC, C10 or other excipients of the investigational medicinal product (IMP) at screening.

2. Participants with one of the following prior or existing medical history or conditions:

   1. Participants with cardiovascular system, digestive system, respiratory system, urinary system, blood system, nervous system, psychiatric disorders, endocrine diseases (except obesity or overweight), malignant tumors and other diseases that are judged by the investigator to have an impact on the evaluation of the results of this study.
   2. Diseases that increase the risk to participants, such as hypoglycemia, acute or chronic pancreatitis, history of pancreatic surgery or trauma, and history of symptomatic gallbladder disease; cholelithiasis with a high risk of acute biliary pancreatitis at screening (such as sand-like stones, and gallbladder and bile duct stones ≤ 5 mm in diameter); newly diagnosed cholecystitis at screening;
   3. History or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2;
   4. Participants with clinically significant digestive system diseases who are judged unsuitable for the study by the investigator, such as history of active peptic ulcer or hemorrhage, inflammatory bowel disease, abnormal gastric emptying (such as gastroparesis or pyloric stenosis, gastric outlet obstruction), continuous use of drugs affecting gastrointestinal motility for ≥ 1 week (including but not limited to domperidone, mosapride, macrolides), and acute hemorrhoidal attacks within the past three months;
   5. Participants with severe infection or unexplained infection within 4 weeks before screening.

3. Participants with a weight change > 5.0% within 12 weeks prior to screening.

4. Participants who have any clinically significant abnormalities in 12-lead ECG, vital signs (blood pressure, respiration, pulse and body temperature), physical examinations, imaging procedures or laboratory tests (hematology, urinalysis, blood biochemistry and coagulation) at screening or predose as judged by the investigator to be unsuitable for participation in this study, or whose laboratory test items at screening, on D-2 or D-1 meet any of the following criteria:

   1. eGFR <90 mL/min/1.73 m2;
   2. Hemoglobin A1c (HbA1c) ≥ 6.5%;
   3. FPG ≥ 7.0 mmol/L;
   4. Two-hour venous plasma glucose > 11.1 mmol/L after a 75 g oral glucose tolerance test (OGTT);
   5. Calcitonin ≥ 20 pg/mL;
   6. Those who are positive for four tests for infectious diseases.

5. Those who have undergone bariatric surgery (except for acupuncture weight loss, liposuction, and abdominoplasty performed more than 1 year before screening), those who have had major surgery within 6 months prior to screening, or those who schedule to have surgery or hospitalization during the study.

6. Participants who have received any vaccine within 1 month before screening, or plan to receive any vaccine during the study.

7. Use of any prescription drugs, over-the-counter drugs or Chinese herbal medicines within 2 weeks prior to screening; or use of any GLP-1R agonists or drugs with the same mechanism of action as GLP-1R agonists [such as GLP-1R/glucagon receptor (GCGR) agonists or glucose-dependent insulinotropic polypeptide receptor (GIPR)/GLP-1R agonists or GIPR/GLP-1R/GCGR agonists) within 6 months prior to screening; or use of any weight loss drugs within 6 months prior to screening or use of concomitant medications from the screening period to before the first dose.

8. Participation in other interventional clinical trials before screening (within the past 3 months or within 5 half-lives after administration of the investigational drug, whichever is longer). Or plan to participate in another clinical study of an IMP, surgery, or device before completing all scheduled assessments in the clinical study.

9. Those who have donated blood or blood products (> 100 mL) or lost a large volume of blood (> 400 mL) within 2 months prior to screening or have planned to donate blood or blood products during the study.

10. History of drug abuse within 1 year prior to screening; or positive results for drug abuse on D-2.

11. History of alcohol abuse within 3 months prior to screening, defined as an average intake of more than 14 units per week (1 standard unit = 360 mL of beer or 150 mL of 12% wine or 45 mL of 40% spirits); or use of any alcohol-containing products 48 hours before dosing and throughout the study; or abnormal results for breath alcohol test on D-2.

12. Female participants who are pregnant or lactating, or have a positive human chorionic gonadotropin (β-HCG) pregnancy test at screening.

13. Participants who are allergic to any food or have specific dietary requirements and cannot adhere to a standardized diet.

14. Unwillingness to undergo repeated venipuncture due to poor tolerance or difficult venous access, or participant experiences needle or blood phobia.

15. Any condition that, in the investigator's opinion, renders the participant unsuitable for participation in this study, including potential compromise of the participant's rights.

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