Dose-escalation and Food Effect Study of ZT006 in Healthy, Overweight and Obese Participants

• ZT006 (Drug): Participants will receive a single dose of ZT006 of dose level 1 under fasted condition.
• ZT006 (Drug): Participants will receive a single dose of ZT006 of dose level 2 under fasted condition.
• ZT006 (Drug): Participants will receive a single dose of ZT006 of dose level 3 under fasted condition.
• ZT006 (Drug): Participants will receive a single dose of ZT006 of dose level 4 under fasted condition in period 1, and after a high fat, high caloric breakfast in period 2.
• ZT006 (Drug): Participants will receive a single dose of ZT006 of dose level 5 under fasted condition.
• ZT006 (Drug): Participants will receive daily doses of ZT006 for 42 days: dose level 1 for 7 days, then dose level 2 for 7 days, then dose level 3 for 28 days.
• ZT006 (Drug): Participants will receive daily doses of ZT006 for 42 days: dose level 1 for 7 days, then dose level 2 for 7 days, then dose level 3 for 14 days, then dose level 4 for 14 days.
• ZT006 (Drug): Participants will receive daily doses of ZT006 for 42 days: dose level 2 for 7 days, then dose level 3 for 7 days, then dose level 4 for 28 days.
• ZT006 (Drug): Participants will receive daily doses of ZT006 for 42 days: dose level 2 for 7 days, then dose level 3 for 7 days, then dose level 4 for 14 days, then dose level 5 for 14 days.
• Placebo of ZT006 (Drug): Participants will receive a single dose of placebo of ZT006 under fasted condition.
• Placebo of ZT006 (Drug): Participants will receive a single dose of placebo of ZT006 under fasted condition in period 1, and after a high fat, high caloric breakfast in period 2.
• Placebo of ZT006 (Drug): Participants will receive daily doses of placebo of ZT006 for 42 days.

Primary outcomes

• Rate of treatment-emergent adverse events after single dose administration under fasted condition. [From baseline to Day 43]: Summarized from adverse event reporting in %
• Rate of treatment-emergent adverse events during and after multiple-dose administration. [From baseline to end of study (Day 77)]: Summarized from adverse event reporting in %
• Rate of treatment-emergent adverse events after single dose administration under fed condition. [From Day 44 to end of study (Day 86)]: Summarized from adverse event reporting in %

Secondary outcomes

• Area under the concentration-time curve from time zero to infinity after single-dose administration under fasted condition. [From baseline to Day 43]: Measured in ng*h/mL
• Maximal observed concentration after single-dose administration under fasted condition. [From baseline to Day 43]: Measured in ng/mL
• Time to reach the maximal observed concentration after single-dose administration under fasted condition. [From baseline to Day 43]: Measured in hours
• Terminal half-life after single-dose administration under fasted condition. [From baseline to Day 43]: Measured in hours
• Area under the concentration-time curve during the dosing interval at steady state. [Day 42 to Day 77]: Measured in ng*h/mL
• Maximal observed concentration at steady state. [Day 42 to Day 77]: Measured in ng/mL
• Time to reach the maximal observed concentration at steady state. [From Day 42 to Day 77]: Measured in hours
• Terminal half-life at steady state. [From Day 42 to Day 77]: Measured in hours
• Area under the concentration-time curve from time zero to infinity after single-dose administration under fed condition. [From Day 44 to end of study (Day 86)]: Measured in ng*h/mL
• Maximal observed concentration after single-dose administration under fed condition. [From Day 44 to end of study (Day 86)]: Measured in ng/mL
• Time to reach the maximal observed concentration after single-dose administration under fed condition. [From Day 44 to end of study (Day 86)]: Measured in hours
• Terminal half-life after single-dose administration under fed condition. [From Day 44 to end of study (Day 86)]: Measured in hours
• Incidence of ZT006 anti-drug antibody after single-dose administration under fasted condition. [From baseline to Day 43]: Measured in %
• Incidence of ZT006 anti-drug antibody during and after multiple-dose administration. [From baseline to end of study (Day 77)]: Measured in %

Sex: All, ages: 18 Years to 55 Years, accepts healthy volunteers

Inclusion Criteria:

* Considered to be generally healthy based on the medical history, physical examination, and the results of vital signs, 12-lead electrocardiogram and clinical laboratory tests (hematology, urinalysis, chemistry, coagulation), as judged by the investigator.
* Male or female, age between 18 - 55 years (both inclusive) at the time of signing of the informed consent.
* Body mass index (BMI) 19.0 - 35.0 kg/m²(both inclusive). Body weight >50.0 kg for male participants and >45.0 kg for female participants. BMI 19 - 28.0 kg/m²(both inclusive) for single-dose escalation study, BMI 19.0 - 28.0 kg/m²(both inclusive) for cohorts 1 and 2 of multiple-dose escalation study, BMI 24.0 - 35.0 kg/m²(both inclusive) for cohorts 3 and 4 of multiple-dose escalation study.
* Having dietary caloric restriction and increased physical activity for ≥3 months, with change in body weight (increase or decrease) no more than 5%, irrespective of medical records.

Exclusion Criteria:

* Known hypersensitivity to the study drug or excipients or GLP-1 receptor agonists.
* Medical history of hypoglycemia.
* History or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2, or history of pancreatitis or symptomatic gallbladder disease.
* Previous diagnosis of endocrine disorders or monogenic mutations causing obesity, including but not limited to hypothalamic obesity, pituitary obesity, hypothyroidism-induced obesity, Cushing's syndrome, insulinoma, acromegaly, or hypogonadism.
* Use of GLP-1 receptor agonists within 30 days or 5 half-lives (whichever is longer) before the first dose of the investigational intervention.
* Glycated hemoglobin (HbA1c) > 6.0% or fasting plasma glucose < 3.9 mmol/L or > 6.1 mmol/L at screening, or diagnosed with diabetes mellitus of type 1 or type 2 diabetes or other specific types derived from other causes.
* Aspartate aminotransferase ≥ 2 × upper limit of normal (ULN), Alanine aminotransferase ≥ 2 × ULN, or total bilirubin ≥ 1.5 × ULN
* Calcitonin above ULN at screening.
* Other clinically significant diseases detected within 12 months before screening (including but not limited to gastrointestinal, renal, hepatic, neurological, hematological, endocrine, oncological, pulmonary, immunological, psychiatric, or cardiovascular diseases).
* Use of prescription drugs (excluding topical eye/nose drops and creams without systemic exposure risk), over-the-counter drugs, dietary supplements, vitamins, or herbal medicines (excluding routine vitamins) within 2 weeks before screening.
* Long-term use of medications directly affecting gastrointestinal motility prior to screening. Use of weight-loss medications (including but not limited to orlistat) within 3 months before dosing.

• Wei Hu, MD, Principal investigator, The Second Hospital of Anhui Medical University
• Yijun Du, Master, Principal investigator, The Second Hospital of Anhui Medical University