A Multicenter, Randomized, Double-blind, Parallel, Placebo-controlled Phase II Study Assessing the Efficacy and Safety of DA-302168S Tablets in Subjects With Type 2 Diabetes Mellitus.
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 272
- 试验地点
- 1
- 主要终点
- Change from baseline in HbA1c
研究概览
简要总结
This Phase II, multicenter, randomized, double-blind, placebo-controlled, parallel-group study aims to assess the efficacy, safety, and PK characteristics of DA-302168S tablets in Chinese T2DM participants, and to provide dose-selection evidence for the Phase III confirmatory trial.
详细描述
This Phase II study is designed to enroll approximately 272 adult participants with T2DM. A total of 260 participants will be randomized in a 1:1:1:1:1 ratio to receive DA-302168S at 5 mg, 10 mg, 15 mg, or 20 mg, or matching placebo. An additional open-label cohort (Cohort 5) will enroll 12 participants, all treated with the investigational product at the target dose of 20 mg. The study comprises a screening period of up to 2 weeks, a 4-week run-in period, a 16-week treatment phase, and a 2-week safety follow-up.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 to 75 years (inclusive), both sexes.
- •Diagnosed with T2DM according to the Chinese Diabetes Prevention and Treatment Guidelines (2024 Edition) for at least 3 months at screening, and meeting one of the following: (1) on stable metformin monotherapy for ≥8 weeks prior to screening, with a daily dose of ≥1500 mg/day or maximum tolerated dose ≥1000 mg/day, in addition to diet and exercise; stable treatment defined as no change in daily dose; (2) glycemic control by diet and exercise alone for ≥8 weeks prior to screening.
- •HbA1c (local laboratory) ≥7.5% and ≤11.0% at screening; and HbA1c (central laboratory) ≥7.5% and ≤10.5% at randomization.
- •BMI 22.5-40 kg/m² (inclusive), and stable body weight for 3 months prior to screening (weight change <5%, calculated as [max weight - min weight] / max weight × 100%).
排除标准
- •History of type 1 diabetes, diabetes due to pancreatic injury, or other types of diabetes (excluding gestational diabetes) other than T2DM.
- •Acute diabetic complications (e.g., diabetic ketoacidosis, lactic acidosis, or hyperosmolar nonketotic coma) within 6 months prior to ICF signing; history of grade 3 hypoglycemia within 6 months prior to ICF signing, or ≥3 episodes of hypoglycemia (blood glucose <3.9 mmol/L) from 1 month before screening to randomization.
- •Clinically significant active infection or other diseases (including but not limited to neurological, psychiatric, cardiovascular, endocrine, digestive, respiratory, urinary, hematological, or immunological disorders, except those related to T2DM) within 6 months prior to screening that, in the investigator's judgment, may interfere with trial results or pose additional risks with study drug administration.
- •Endocrine diseases or history that may significantly affect body weight (e.g., Cushing's syndrome, obesity due to pituitary or hypothalamic disorders), or obesity due to monogenic mutations or genetic obesity syndromes.
- •Evidence of significant active autoimmune abnormalities (e.g., lupus or rheumatoid arthritis) requiring systemic glucocorticoid therapy during the trial, as judged by the investigator.
- •Severe chronic diabetic complications at screening (e.g., proliferative retinopathy or maculopathy, painful diabetic neuropathy, intermittent claudication, or diabetic foot).
- •History or family history of medullary thyroid carcinoma, thyroid C-cell hyperplasia, or multiple endocrine neoplasia type
- •Hyperthyroidism (including clinical and subclinical) at screening, or hypothyroidism not controlled with stable medication dose (defined as stable dose for ≥3 months with normal thyroid function tests) based on local laboratory reference ranges.
- •History of acute pancreatitis, or prior chronic pancreatitis or pancreatic injury, or other high-risk factors for pancreatitis.
- •Acute cholecystitis within 3 months prior to ICF signing, or presence of cholecystitis/cholangitis/bile duct stones/multiple gallstones at screening, or gallbladder-related conditions at screening that, in the investigator's judgment, may predispose to cholecystitis (except those who have undergone cholecystectomy and are deemed eligible by the investigator).
- •Dysphagia or history of gastrointestinal disorders affecting drug absorption, including but not limited to gastrectomy or resection of any intestinal segment, severe gastrointestinal disease, or clinically evident gastric emptying abnormalities.
- •Uncontrolled or unstable hypertension at screening, defined as SBP ≥160 mmHg and/or DBP ≥100 mmHg despite regular antihypertensive treatment, or evidence of renal artery stenosis or unstable blood pressure (including orthostatic hypotension).
- •Clinically significant cardiovascular or cerebrovascular diseases, including but not limited to the following events within 6 months prior to ICF signing or during the run-in period: a. unstable angina; b. heart failure (NYHA class III or IV); c. myocardial infarction; d. coronary artery bypass grafting or percutaneous coronary intervention; e. uncontrolled severe arrhythmias, such as sick sinus syndrome, second- or third-degree atrioventricular block; f. cerebrovascular accidents, such as cerebral infarction or transient ischemic attack.
- •Hemoglobinopathies or anemia, such as hemolytic anemia or sickle cell anemia.
- •History of moderate or severe depression, or PHQ-9 score ≥15 at screening (see Appendix 2), or psychiatric disorders that, in the investigator's opinion, may affect participation.
- •Electrocardiogram abnormalities during screening or run-in: heart rate <50 bpm or >100 bpm; QTcF (Fridericia-corrected) >450 ms (male) or >470 ms (female).
研究组 & 干预措施
DA-302168S
Cohort 1-5mg dose group：Participants will receive DA-302168S tablets once daily orally, 16weeks.
Cohort 2-10mg dose group：Participants will receive DA-302168S tablets once daily orally, 16weeks.
Cohort 3-15mg dose group：Participants will receive DA-302168S tablets once daily orally, 16weeks.
Cohort 4-20mg dose group：Participants will receive DA-302168S tablets once daily orally, 16weeks.
Cohort 5-20mg dose group：Participants will receive DA-302168S tablets once daily orally, 10weeks.
干预措施: DA-302168S (Drug)
Placebo of DA-302168S
Cohort 1-5mg dose group：Participants will receive matching placebo tablets orally once daily for 16 weeks.
Cohort 2-10mg dose group：Participants will receive matching placebo tablets orally once daily for 16 weeks.
Cohort 3-15mg dose group：Participants will receive matching placebo tablets orally once daily for 16 weeks.
Cohort 4-20mg dose group：Participants will receive matching placebo tablets orally once daily for 16 weeks.
干预措施: Placebo of DA-302168S (Drug)
结局指标
主要结局
Change from baseline in HbA1c
时间窗: From baseline (week 1) to week 16
measured in %
次要结局
- Percentage of participants with HbA1c <7.0% and ≤6.5%(From baseline (week 1) to week 16)
- Change from baseline in fasting lipid profile(From baseline (week 1) to week 16)
- Change from baseline in systolic and diastolic blood pressure(From baseline (week 1) to week 16)
- Adverse events, including treatment-emergent adverse events (TEAEs), serious adverse events (SAEs)(From baseline (week 1) to week 18)
- Change from baseline in fasting C-peptide(From baseline (week 1) to week 16)
- Change from baseline in fasting insulin(From baseline (week 1) to week 16)
- Change from baseline in fasting glucagon(From baseline (week 1) to week 16)
- Change from baseline in fasting blood glucose(From baseline (week 1) to week 16)
- Percent changes from baseline in body weight(From baseline (week 1) to week 16)