HDM1002 tablets for adults with type 2 diabetes

A Phase 3, Randomized, Double-blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of HDM1002 Tablets in Subjects With Type 2 Diabetes Mellitus Inadequately Controlled With Diet and Exercise Only

This study will test whether once-daily HDM1002 tablets can help lower blood sugar in adults with type 2 diabetes who are managing their condition with diet and exercise only.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 360 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd. (Industry-sponsored)
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT07193459 on ClinicalTrials.gov

What this trial studies

This is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial enrolling about 360 adults with type 2 diabetes not currently taking glucose-lowering drugs. After a screening and 2-week placebo run-in, participants are randomized 1:1:1 to receive HDM1002 200 mg, HDM1002 400 mg, or placebo once daily with dose escalation every 4 weeks until target doses are reached. Participants are stratified by baseline HbA1c (≤ 8.5% or > 8.5%), treated for 52 weeks, and followed for approximately 4 weeks after the last dose. The primary endpoint will be evaluated at Week 40.

Who should consider this trial

Good fit: Adults aged 18–75 with type 2 diabetes for at least 10 weeks who have been managing with diet and exercise only, have HbA1c between 7.5% and 10.5%, and a BMI of 22.5–40 kg/m2 are ideal candidates.

Not a fit: People with type 1 diabetes, those currently taking or recently treated with hypoglycemic drugs, those with HbA1c or BMI outside the specified ranges, or who cannot attend visits in Beijing are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, HDM1002 could offer an oral GLP-1 receptor agonist option to help improve blood sugar control for adults with type 2 diabetes who are not using diabetes medications.

How similar studies have performed: Other GLP-1 receptor agonists, including oral formulations, have successfully lowered HbA1c and body weight in type 2 diabetes, so the approach has precedent even though HDM1002 itself is novel.

Eligibility criteria

Inclusion Criteria:

1. Male or female subjects between 18 and 75 years of age (inclusive).
2. Have been diagnosed with type 2 diabetes mellitus (T2DM) for at least 10 weeks based on the World Health Organization, and meet the following conditions:a) had been treated with diet and exercise for at least 10 weeks prior to signing ICF; b) Not been treated with any hypoglycemic drugs within 10 weeks prior to signing ICF.
3. HbA1c ≥7.5% and ≤10.5% at screening as assessed by the local laboratory, and HbA1c ≥7.5% and ≤10.5% prior to randomization as assessed by the specified central laboratory.
4. Having a body mass index (BMI) of 22.5 to 40.0 kg/m2, inclusive.
5. Female participants of childbearing potential and male participants must agree to use highly effective contraception method from the day of signing the ICF and until 30 days (female) or 90 days (male) after the final dose administration.
6. Able to understand and comply with protocol requirements, agree to maintain the same dietary and exercise habits throughout the trial, be willing to complete the trial in strict compliance with the clinical trial protocol and provide written informed consent.

Exclusion Criteria:

1. Diagnosed with type 1 diabetes mellitus (including latent autoimmune diabetes in adults), special types of diabetes or gestational diabetes mellitus
2. Evidence of acute complications of diabetes (e.g., diabetic ketoacidosis, diabetic lactosidosis, or hyperosmolar nonketotic coma) within 6 months prior to signing ICF.
3. Have a known self or family history of medullary thyroid carcinoma, thyroid C-cell hyperplasia or multiple endocrine neoplasia type II (MEN2)
4. History of acute or chronic pancreatitis or pancreatic injury, or any high-risk factor which may lead to pancreatitis; or have symptomatic gallbladder disease that requires treatment during the trial (subjects with prior cholecystectomy can be enrolled if deemed eligible by the investigator)
5. Have had dysphagia, or any condition or disease possibly affecting gastric emptying or nutrients absorption in the opinion of the investigator, such as history of surgery affecting gastric emptying, gastroesophageal reflux disease, pyloric obstruction, irritable bowel syndrome, etc.
6. Have had any of the following within 3 months prior to screening:

   * Unstable angina；
   * Heart failure (New York Heart Association, class III or IV);
   * Myocardial infarction (MI)；
   * Coronary artery bypass grafting or percutaneous coronary intervention；
   * Uncontrolled severe arrhythmias (including: ventricular tachycardia, ventricular fibrillation, atrial fibrillation, second to third degree atrioventricular block, sick sinus node syndrome, pre-excitation syndrome, etc.)；
   * Cerebrovascular accident
7. Have a history of proliferative diabetic retinopathy and/or diabetic maculopathy that requires treatment, or evidence of other severe retinopathy that requires treatment during the study.
8. Have a known history of liver disease, including: acute or chronic active liver disease (except non-alcoholic steatohepatitis) such as active hepatitis B, hepatitis C; or primary biliary cholangitis.
9. Those who have used the following drugs within 14 days before randomization or within 5 half-lives (whichever is longer), or who need to use the following drugs for a long time during the trial, are excluded: strong or moderate inhibitors of cytochrome P450 enzyme (CYP) 3A4, strong inducers of CYP3A4, strong inhibitors of P-gp, strong inducers of P-gp, inhibitors of OATP1B1 or OATP1B3, or narrow therapeutic index drugs that are CYP2C8, CYP3A4, UGT1A1, P-gp, OATP1B1 or OATP1B3 substrates.
10. Use of any glucose-lowering medication within 10 weeks prior to signing ICF, including but not limited to: α-glucosidase inhibitors (e.g., acarbose), thiazolidinediones, and dipeptidyl peptidase-4 inhibitors (DPP-4i) inhibitors, glucose kinase activators, sodium-glucose cotransporter-2 inhibitors (SGLT-2i) ,with the exception of short-term insulin therapy due to a concomitant illness, stress, or perioperative period (cumulative duration ≤ 14 days).
11. Having used a Glucagon-like peptide-1 (GLP-1) analogue within 3 months prior to signing the ICF; or previous discontinuation of a GLP-1 analogue due to safety/tolerability or lack of efficacy.
12. Pregnancy or lactation.
13. Subjects with a known hypersensitivity to GLP-1 receptor agonists (GLP-1RA), or a history of severe drug allergies.
14. Enrolled in or participated in any other clinical study of drugs or medical devices within 3 months (or within 5 half-lives, whichever is longer) prior to signing the ICF (except for subjects who signed written informed consent without any intervention of investigational product or medical devices).
15. Any other condition considered by the investigator which is not suitable for participating in this study.

Where this trial is running

Beijing, Beijing Municipality

• Peking University People's Hospital — Beijing, Beijing Municipality, China (Recruiting)

Conditions Type 2 Diabetes; Glucagon-Like Peptide-1 Receptor Agonists; HDM1002 tablet; type 2 diabetes