Multiple Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Efficacy of THDBH120 in Chinese Patients With T2DM

Multiple Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Efficacy of THDBH120 in Chinese Patients With T2DM: A Randomized, Bouble-Blind, Placebo-Controlled Phase Ib Trial

The aim of this trial is to investigate the safety, tolerability, pharmacokinetics, and efficacy of THDBH120 injection in participants with T2DM. This study includes three multiple-ascending dose cohorts.

Inclusion Criteria:

• Male or female patients 18 to 75 years of age, inclusive;
• Have T2DM for at least 6 months before screening based on the disease diagnostic criteria (World Health Organization [WHO] Classification for Diabetes);
• Treated with diet and exercise alone, or a stable dose of metformin (≥1000 mg/day and not more than the locally approved dose) for at least 2 months prior to screening;
• Have a BMI between 23 and 35 kg/m²(inclusive) at screening;
• HbA1c levels: 7.0% to 10.0% (inclusive) for subjects treated by diet or exercise alone; 7.0% to 9.0% (inclusive) for subjects receiving stable-dose metformin.

Exclusion Criteria:

• Have been diagnosed with proliferative diabetic retinopathy, diabetic maculopathy, or non-proliferative diabetic retinopathy requiring treatment during the study;
• Have a personal or family history of medullary thyroid carcinoma or have multiple endocrine neoplasia type 2;
• Have diagnosed hyperthyroidism or hypothyroidism;
• Have grade 2 hypoglycemia events or grade 3 hypoglycemia events within 6 months prior to screening;
• Have a history of ketoacidosis, lactic acidosis, or hyperosmolar state leading to hospitalization within 6 months prior to screening;
• Presence of uncontrolled hypertension at screening: systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg;
• Prolonged QTcF interval on 12-lead ECG at screening (QTcF≥450 ms for males, >470 ms for females), PR interval >200 ms, or the presence of long QT syndrome, second- or third-degree atrioventricular block, left or right bundle branch block, Wolff-Parkinson-White syndrome, or any other clinically significant arrhythmias (except sinus arrhythmia);
• Weight change ≥ 5% within 3 months prior to screening;
• Have been treated with insulin, excluding insulin therapy for gestational diabetes mellitus, or acute/temporary insulin therapy (≤ 14 days) for conditions such as acute illness, hospitalization, or elective surgery.