Overview
This study is a multicenter, randomized, double-blind, placebo-controlled Phase III clinical study aimed at evaluating the efficacy, safety, and pharmacokinetic (PK) characteristics of DA-302168S tablets in overweight or obese participants in China.
Description
This study will be divided into three phases: a screening period (up to 2 weeks), a treatment period (52 weeks), and a safety follow-up period (2 weeks). The study plans to enroll approximately 840 participants. Eligible participants will be randomly assigned in a 1:1:1 ratio to the 10 mg dose group, the 20 mg dose group, or the placebo group, with each dose group planned to enroll about 280 participants. During the treatment period, all participants should adhere to dietary and exercise control, with guidance on diet and energy intake provided by authorized nutritionists or investigators.
Eligibility
Key Inclusion Criteria:
- Age 18-75 years (inclusive), both males and females;
- BMI requirements at screening: for obese participants, BMI ≥28 kg/m² with or without comorbidities; or for overweight participants, BMI ≥24.0 kg/m² and \<28 kg/m² with at least one of the following comorbidities: hypertension, prediabetes, dyslipidemia, weight-bearing joint pain (as determined by the investigator, excluding joint pain caused by other diseases), obstructive sleep apnea syndrome, or metabolic dysfunction-associated steatotic liver disease;
- Body weight change \<5% (based on participant self-report, calculated as \[maximum weight - minimum weight\] / maximum weight, with the result rounded to one significant digit) during the 3 months prior to screening, while on diet and exercise control (based on participant self-report).
Exclusion Criteria:
- Type 1 diabetes, type 2 diabetes, or other specific types of diabetes (excluding gestational diabetes);
- Secondary obesity, history of bariatric surgery;
- Presence of gastrointestinal diseases affecting drug absorption, dysphagia;
- Personal/family history of medullary thyroid carcinoma, C-cell hyperplasia, or multiple endocrine neoplasia type 2; uncontrolled hyperthyroidism or hypothyroidism without standard stable management; thyroid nodule with TI-RADS grade 4 or above;
- History of acute pancreatitis, chronic pancreatitis, or pancreatic injury within 6 months prior to screening (high-risk pancreatic conditions); acute cholecystitis within the past 3 months, or current cholecystitis, cholangitis, cholelithiasis, or other high-risk gallbladder diseases (except for those with prior cholecystectomy and judged eligible by the investigator);
- Severe unstable psychiatric disorder, depression, or history of suicide attempt; score ≥15 on the Patient Health Questionnaire-9 (PHQ-9) at screening, or presence of suicidal ideation/suicidal behavior indicated by the Columbia-Suicide Severity Rating Scale (C-SSRS);
- Any of the following abnormal clinical laboratory results (local laboratory) at screening: anemia (hemoglobin \<110 g/L for males, \<100 g/L for females); liver enzymes, bilirubin, amylase, or lipase exceeding the specified multiples of the upper limit of normal; calcitonin ≥50 ng/L (pg/mL); estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73m²; triglycerides \>5.65 mmol/L; thyroid-stimulating hormone \>6 mIU/L or \<0.4 mIU/L;
- Uncontrolled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg);
- Abnormal heart rate on resting electrocardiogram, atrioventricular block, prolonged QTcF interval, bundle branch block, or other clinically significant arrhythmias; history of myocardial infarction, unstable angina, severe cardiac insufficiency, coronary intervention/bypass, or other cardiovascular/cerebrovascular diseases within 6 months prior to enrollment;
- Use of weight-loss drugs or weight-loss herbal medicines, any hypoglycemic agents, antidepressants, antipsychotics, antiepileptics, or lithium salts within 3 months prior to screening; use of systemic glucocorticoids (except for continuous cumulative use \<7 days); active autoimmune disease requiring systemic glucocorticoid therapy during the study period.
