Type 2 Diabetes Mellitus
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGDA-302168S
A small molecule GLP-1R agonist tablet, orally administration, once daily，16weeks.
Matching placebo tablet will be provided
Sponsors
Chendu DIAO Pharmaceutical Group CO., LTD.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Age 18 to 75 years (inclusive), both sexes. 2. 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. 3. HbA1c (local laboratory) ≥7.5% and ≤11.0% at screening; and HbA1c (central laboratory) ≥7.5% and ≤10.5% at randomization. 4. 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%). Key
Exclusion criteria
1. History of type 1 diabetes, diabetes due to pancreatic injury, or other types of diabetes (excluding gestational diabetes) other than T2DM. 2. 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. 3. 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. 4. 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. 5. Evidence of significant active autoimmune abnormalities (e.g., lupus or rheumatoid arthritis) requiring systemic glucocorticoid therapy during the trial, as judged by the investigator. 6. Severe chronic diabetic complications at screening (e.g., proliferative retinopathy or maculopathy, painful diabetic neuropathy, intermittent claudication, or diabetic foot). 7. History or family history of medullary thyroid carcinoma, thyroid C-cell hyperplasia, or multiple endocrine neoplasia type 2. 8. 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. 9. History of acute pancreatitis, or prior chronic pancreatitis or pancreatic injury, or other high-risk factors for pancreatitis. 10. 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). 11. 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. 12. 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). 13. 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. 14. Hemoglobinopathies or anemia, such as hemolytic anemia or sickle cell anemia. 15. 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. 16. Electrocardiogram abnormalities during screening or run-in: heart rate \<50 bpm or \>100 bpm; QTcF (Fridericia-corrected) \>450 ms (male) or \>470 ms (female).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in HbA1c | From baseline (week 1) to week 16 | measured in % |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants with HbA1c <7.0% and ≤6.5% | From baseline (week 1) to week 16 | percentage-point |
| Change from baseline in fasting blood glucose | 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 | — |
| Percent changes from baseline in body weight | 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 | — |
Countries
China
Contacts
CONTACTxiaolong qin
Outcome results
None listed