This is a randomized, double-blind, placebo controlled, parallel group study, which aims to provide data on efficacy, safety and pharmacokinetics (PK) of multiple dose levels of HDM1002 tablets in adults with type 2 diabetes mellitus (T2DM) inadequately controlled on metformin and/or diet and exercise.
This phase 2, 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 on metformin monotherapy or diet and exercise alone. At least 80% of the enrolled participants are required to be on metformin prior to screening. A total of 318 participants will be included in this study, and will be stratified according to baseline glycated hemoglobin (HbA1c) (≤ 8.5% or \> 8.5%) and background diabetes treatment (metformin or diet and exercise alone). For cohort A to cohort E, approximately 293 participants will be randomized in a 57:57:57:65:57 ratio to receive different doses of HDM1002 or placebo. In addition, an open-label design will be used in cohort F to explore the efficacy and safety of HDM1002 tablets administered in 200 mg twice daily. About 25 participants will be enrolled in cohort F, all of which will receive HDM1002 tablets. Following the screening period to confirm eligibility up to 2-weeks, the study will consist of a 2-week placebo run-in period (participants with diet and exercise alone) or a 6-week metformin run-in period (participants with metformin prior to screening) prior to randomization on Day 1. The treatment period will be 12 weeks, followed by an approximate 4-week follow-up. Dosing will occur with or without food once daily or twice daily, and up to 4 weeks of dose titration regimen will be adopted to maximize tolerability of HDM1002.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
324
HDM1002 tablets, 50 mg once daily, 12 weeks
HDM1002 tablets, 100 mg once daily, 12 weeks
HDM1002 tablets, 200 mg once daily, 12 weeks
Change From Baseline in HbA1c at Week 12
HbA1c can be used as a diagnostic test for diabetes and is a widely recognized objective measure of glycemic control
Time frame: Baseline, Week 12
Change From Baseline in HbA1c at Week 4, Week 8
HbA1c can be used as a diagnostic test for diabetes and is a widely recognized objective measure of glycemic control
Time frame: Baseline, Week 4, Week 8
Percentage of Participants With an HbA1c target value of < 7.0% or ≤ 6.5%
The target HbA1c level for people with diabetes is usually less than 7%.
Time frame: Baseline, Week 12
Change From Baseline in Fasting plasma Glucose
The fasting plasma glucose measures the levels of glucose in the blood, with a normal range of 70 mg/dL to 99 mg/dL.
Time frame: Baseline, Week 12
Change From Baseline in Postprandial 2-hour Glucose (PPG2h), Area Under the Curve of Plasma Glucose (AUC0-4h, Glucose), C-Peptide (AUC0-4h, C-peptide), Insulin (AUC0-4h, Insulin), and Glucagon (AUC0-4h, Glucagon)
These indicators were assessed using the mixed-meal tolerance test
Time frame: Baseline, Week 12
Change From Baseline in Fasting C-Peptide, Fasting Insulin, and Fasting Glucagon
C-Peptide, Fasting Insulin, and Fasting Glucagon were measured at planned time points
Time frame: Baseline, Week 12
Change From Baseline in Homeostasis Model Assessment of β-Cell Function (HOMA-β) and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)
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HDM1002 tablets, 400 mg once daily, 12 weeks
HDM1002 tablets, 200 mg twice daily, 12 weeks
Matching placebo will be provided
The Chinese People's Liberation Army General Hospital
Beijing, Beijing Municipality, China
Beijing Chaoyang Hospital Affiliated to Capital Medical University
Beijing, China
Peking University Shougang Hospital
Beijing, China
Cangzhou Central Hospital
Cangzhou, China
The Second Hospital of Jilin University
Changchun, China
The Fourth Hospital of Changsha City
Changsha, China
The Third Hospital of Changsha City
Changsha, China
Chengdu Second People's Hospital
Chengdu, China
The Affiliated Hospital of Chengdu University
Chengdu, China
Three Gorges Hospital Affiliated to Chongqing University
Chongqing, China
...and 21 more locations
HOMA-IR and HOMA-β are commonly used to estimate insulin resistance and beta cell function.
Time frame: Baseline, Week 12
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)]
Fasting Lipid Profiles were measured at planned time points.
Time frame: Baseline, Week 12
Change From Baseline in Systolic and Diastolic Blood Pressure
Blood Pressure was measured using an automated device
Time frame: Baseline, Week 12
Change From Baseline in Body Weight
Weight was recorded in kilograms (kg), and accuracy to the nearest 0.1 kg.
Time frame: Baseline, Week 12
Percentage of Participants Achieving Weight Loss ≥ 5% and ≥ 10%
Weight was recorded in kilograms (kg), and accuracy to the nearest 0.1 kg.
Time frame: Baseline, Week 12
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.
A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect.
Time frame: Baseline Through Week 16
Number of Participants with Clinical Laboratory Abnormalities, and Abnormalities in Vital Signs, Physical Examination and Electrocardiogram
Vital signs (blood pressure, pulse rate, body temperature, respiratory rate), physical examination, ECG and clinical laboratory evaluations (hematology, clinical chemistry, coagulation, urinalysis, calcitonin, serum amylase and lipase)
Time frame: Baseline Through Week 16