A Phase 1 Study of HEC88473 Injection in Healthy Subjects, Obese Subjects and T2DM Subjects

This study is divided into two parts, Part A is an escalating single-dose study in healthy subjects and obese subjects, and Part B is an escalating multiple-dose study in subjects with T2DM.

Inclusion criteria

Part A

• Males or females, between 18 and 45 years of age, inclusive, at screening.
• Body weight ≥ 50 kg for males and body weight ≥ 45 kg for females. 18≤body mass index (BMI)<28 kg/m2 for nonobese subjects and 28≤BMI≤45 kg/m2 for obese subjects.

Part B

• Males or females, between 18 and 65 years of age, inclusive, at screening.
• 24 kg/m2≤BMI≤35 kg/m2.
• Subjects diagnosed with T2DM, newly diagnosed subjects at screening, or treated with diet and exercise alone within 3 months before screening and still have poor blood glucose control, or treated with a stable dose of metformin for ≥ 3 months before screening.
• 7.0%≤ HbA1c ≤10.5% at screening.

Exclusion criteria

Part A

• Smoked more than 5 cigarettes per day within 3 months before the study.
• Immunization with a live attenuated vaccine or coronavirus vaccination within 1 month prior to screening or planned vaccination during the course of the study.
• Positive alcohol breath test result or positive urine drug screen.
• Blood donation (> 300 mL) or massive blood loss (> 400 mL) within 3 months before screening.

Part B

• Have type 1 diabetes mellitus.
• Have had ≥1 episode of severe hypoglycemia within 6 months before screening, or history of recurrent hypoglycemia (history of hypoglycemia more than 3 times in 3 months).
• Have acute or chronic hepatitis, signs and symptoms of any other liver disease other than nonalcoholic fatty liver disease (NAFLD), or alanine aminotransferase (ALT) level >5 times the upper limit of the reference range at screening.
• Have serum calcitonin ≥20 ng/L at screening.
• Have a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2; or have hereditary diseases that can easily induce MTC.
• Fasted triglycerides > 5.7 mmol/L at screening. If the patient is on lipid-lowering therapies, doses must be stable for 30 days prior to screening.