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

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: HSK7653 10 mg Q2W; Drug: HSK7653 25 mg Q2W; Drug: Linagliptin 5 mg QD

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 465
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Peking University People's Hospital
  • Inner Mongolia
    • Baotou, Inner Mongolia, China
      • Inner Mongolia Baogang Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HSK7653 10 mg	Drug: HSK7653 10 mg Q2W; 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.
Experimental: HSK7653 25 mg	Drug: HSK7653 25 mg Q2W; 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.
Active Comparator: Linagliptin 5 mg	Drug: Linagliptin 5 mg QD; 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.

What is the study measuring?

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
Percentage of Patients With HbA1c <7.0%		Baseline, week 24 and week 52
Weight Change From Baseline at Week 24 and Week 52		Baseline, week 24 and week 52
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 <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
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

Collaborators and Investigators

• Sponsor: Sichuan Haisco Pharmaceutical Group Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2020
• Primary Completion (Actual): January 21, 2022
• Study Completion (Actual): August 29, 2022

Study Registration Dates

• First Submitted: September 14, 2020
• First Submitted That Met QC Criteria: September 21, 2020
• First Posted (Actual): September 25, 2020

Study Record Updates

• Last Update Posted (Estimate): December 12, 2022
• Last Update Submitted That Met QC Criteria: December 9, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Linagliptin
• Other Study ID Numbers: HSK7653-302; CTR20201724 (Other Identifier: www.chinadrugtrials.org.cn)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No