HSK7653 Metformin Add-on Study in Patients With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy of HSK7653 (as an add-on to metformin) compared with linagliptin after 24 weeks, and the safety (up to 52 weeks) of HSK7653 in Chinese patients with Type 2 Diabetes who have inadequate glycemic control on diet/exercise therapy and metformin agent monotherapy.

Detailed Description
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The treatment period is composed of a 24-week double-blind period (week 1-24) and a 28-week open-label period (week 25-52). During the double-blind period, participants will receive 10 mg or 25 mg dose of HSK7653, or linagliptin, and with matching placebo respectively. During the open-label period, all participants will receive 25 mg dose of HSK7653. All participants will receive a stable dose of metformin therapy in both the double-blind period and the open-label period.

Official Title
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A Multicenter, Randomized, Double-Blind, Active-Controlled Trial of the Efficacy and Safety of Adding HSK7653 to Metformin in Chinese Patients With Type 2 Diabetes and Inadequate Glycaemic Control

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: HSK7653 10 mg Q2W
* Drug: HSK7653 25 mg Q2W
* Drug: Linagliptin 5 mg QD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 and ≤ 75 years, Male and female patients; Type 2 diabetes mellitus; Insufficient glycaemic control with diet/exercise therapy and metformin agent monotherapy; Did not receive regular long-term medication of oral hypoglycemic drugs (except metformin) or insulin within 1 year prior to informed consent; HbA1c in the range of ≥7.5 to ≤11.0% at screening; FPG < 15 mmol/L at screening; BMI (Body Mass Index) in the range of ≥ 18.0 kg/m² to ≤ 35.0 kg/m² at screening. Exclusion Criteria: Diabetic ketoacidosis, hyperglycemia hypertonic state, serious complications of diabetes, myocardial infarction, stroke within 6 months prior to informed consent; History of severe endocrine disease, uncured cancer, acute pancreatitis prior to informed consent; Current hemoglobinopathy, uncontrolled hypertension, serious nephropathy or hepatopathy prior to informed consent; Serious gastrointestinal disease within 2 weeks prior to informed consent; Serious infection, trauma, and surgery within 3 months prior to informed consent; History of treatment with Dipeptidyl-Peptidase 4 (DPP-4) inhibitor, Glucose-dependent insulinotropic polypeptide (GIP) or Glucagon-like peptide-1 (GLP-1) receptor agonist; Treatment with drugs that affect glucose metabolism within 8 weeks prior to informed consent; Hemoglobin (HGB) < 10.0 g/dL(100 g/L); Alcohol abuse within 6 months or drug abuse history within 5 years prior to informed consent; Active infectious diseases; Participation in another trial with an investigational drug or instrument within 3 months prior to informed consent; Women who are nursing or pregnant, or subjects who have planned parenthood; Contraindication for empagliflozin or linagliptin; Other protocol-defined inclusion/exclusion criteria.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HSK7653 10 mg<br> | Drug: HSK7653 10 mg Q2W<br>* HSK7653 5 mg (2 tablets) and placebo 25 mg (1 tablet) Q2W, placebo of linagliptin 5 mg QD, oral, week 1 to week 24; HSK7653 25 mg Q2W, oral, week 25 to week 52.<br>|
| Experimental: HSK7653 25 mg<br> | Drug: HSK7653 25 mg Q2W<br>* HSK7653 25 mg (1 tablet) and placebo 5 mg (2 tablets) Q2W, placebo of linagliptin 5 mg QD, oral, week 1 to week 24; HSK7653 25 mg (1 tablet) Q2W, oral, week 25 to week 52.<br>|
| Active Comparator: Linagliptin 5 mg<br> | Drug: Linagliptin 5 mg QD<br>* Linagliptin 5 mg QD, placebo of HSK7653 25 mg (1 tablet) and 5 mg (2 tablets) Q2W, oral, week 1 to week 24; HSK7653 25 mg Q2W, oral, week 25 to week 52.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c Change From Baseline at Week 24 | Change From Baseline in Hemoglobin A1c (HbA1c) at Week 24 | Baseline and week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events | The incidence of Treatment-Emergent Adverse Events over time (at week 24 and week 52) | Baseline, week 24 and week 52 | 
| Percentage of Patients With HbA1c <7.0% |  | Baseline, week 24 and week 52 | 
| Percentage of Patients With HbA1c <6.5% |  | Baseline, week 24 and week 52 | 
| FPG Change From Baseline at Week 24 and Week 52 |  | Baseline , week 24 and week 52 | 
| 2h-PPG Change From Baseline at Week 24 and Week 52 |  | Baseline, week 24 and week 52 | 
| Weight Change From Baseline at Week 24 and Week 52 |  | Baseline, week 24 and week 52 | 
| Fasting C-peptide Change From Baseline at Week 24 and Week 52 |  | Baseline, week 24 and week 52 | 
| Insulin Sensitivity Change (Calculated by HOMA-IS) From Baseline at Week 24 and Week 52 |  | Baseline, week 24 and week 52 | 
| Pancreatic β-cell function Change (Calculated by HOMA-β) From Baseline at Week 24 and Week 52 |  | Baseline, week 24 and week 52 | 
| Percentage of Patients Required Use of Rescue Therapy or Dropout due to Hyperglycemia and Week 52 |  | Baseline, week 24 and week 52 |