Study to Evaluate HDM1002 Tablets in Adults With Type 2 Diabetes Mellitus

Official title

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

Overview

This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group study, which aims to provide data on the efficacy and safety of HDM1002 tablets in adults with type 2 diabetes mellitus (T2DM) inadequately controlled with diet and exercise only

Detailed description

This phase 3, multi-center, randomized, double-blind, placebo-controlled, parallel group study aims to assess the efficacy and safety of HDM1002 tablets in adult participants with T2DM inadequately controlled with diet and exercise only. A total of 360 participants will be randomized in this study, and will be stratified according to baseline glycated hemoglobin (HbA1c) (≤ 8.5% or \> 8.5%). Following the screening period to confirm eligibility up to 2-weeks, the study will consist of a 2-week placebo run-in period prior to randomization on Day 1. Eligible participants will be randomized in a 1:1:1 ratio to receive different doses of HDM1002 or placebo once daily for 52 weeks, followed by an approximate 4-week follow-up. During the treatment period, dose escalation will occur every 4 weeks until the target dose is reached. The evaluation of the primary endpoint will be conducted at Week 40

Interventions

• Drug HDM1002 200 mg
  HDM1002 tablets, 200 mg once daily
• Drug HDM1002 400 mg
  HDM1002 tablets, 400 mg once daily
• Drug Placebo
  Placebo tablets, once daily

Primary outcome measures

• Change From Baseline in HbA1c at Week 40 [Time frame: Week 40]

Secondary outcome measures (12)

• Percentage of Participants With an HbA1c target value of < 7.0% or ≤ 6.5% without confirmed (plasma glucose <3.9 mmol/L) symptomatic hypoglycemia [Time frame: Week 40]
• Change from baseline in body weight, body mass index (BMI), and waist circumference [Time frame: Weeks 40]
• Percentage of Participants Achieving Weight Loss ≥ 5% and ≥ 10% [Time frame: Weeks 40]
• Change From Baseline in Fasting plasma Glucose, fasting C-peptide and fasting insulin [Time frame: Weeks 40]
• Change from baseline in daily average levels of 7-point self-monitored blood glucose (SMBG) and mean postprandial glucose increment (all meals) [Time frame: Weeks 40]
• Change From Baseline in Postprandial 2-hour Glucose, C-Peptide, Insulin [Time frame: Weeks 40]
• Change from baseline in homeostasis model assessment of β-cell function (HOMA-β) and insulin resistance (HOMA-IR) [Time frame: Weeks 40]
• Change From Baseline in Fasting Lipid Profiles, including: Low-density Lipoprotein Cholesterol (LDL-C), High-density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Total Cholesterol (TC), Non-HDL-C and Lipoprotein (a) [Lp(a)] [Time frame: Weeks 40]
• Change From Baseline in Systolic and Diastolic Blood Pressure [Time frame: Weeks 40]
• Change from baseline in Diabetes Treatment Satisfaction Questionnaire status version (DTSQs) score [Time frame: Weeks 40]
• Number of Participants With Treatment Emergent Adverse Events (Adverse Events [AEs] and Serious Adverse Events [SAEs]), Adverse Events of Special Interest (AESI), Incidence and Severity of Hypoglycaemic Events, etc. [Time frame: through study completion, an average of 1 year]
• Number of Participants with Clinical Laboratory Abnormalities, and Abnormalities in Vital Signs, Physical Examination, Electrocardiogram and clinical laboratory evaluations [Time frame: through study completion, an average of 1 year]

Eligibility criteria

Inclusion criteria

• Male or female subjects between 18 and 75 years of age (inclusive).
• 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.
• 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.
• Having a body mass index (BMI) of 22.5 to 40.0 kg/m2, inclusive.
• 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.
• 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

• Diagnosed with type 1 diabetes mellitus (including latent autoimmune diabetes in adults), special types of diabetes or gestational diabetes mellitus
• Evidence of acute complications of diabetes (e.g., diabetic ketoacidosis, diabetic lactosidosis, or hyperosmolar nonketotic coma) within 6 months prior to signing ICF.
• Have a known self or family history of medullary thyroid carcinoma, thyroid C-cell hyperplasia or multiple endocrine neoplasia type II (MEN2)
• 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)
• 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.
• 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
• 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.
• 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.
• 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.
• 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).
• 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.
• Pregnancy or lactation.
• Subjects with a known hypersensitivity to GLP-1 receptor agonists (GLP-1RA), or a history of severe drug allergies.
• 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).
• Any other condition considered by the investigator which is not suitable for participating in this study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Peking University People's Hospital — Beijing

Identifiers

NCT: NCT07193459 · HDM1002-302

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗