Long-term Efficacy and Safety of HMS5552 add-on to Metformin in T2DM Subjects

A 24-week Multi-center, Randomized, Double-blind, Placebo-controlled, Phase III Study to Evaluate the Efficacy and Safety of HMS5552 add-on to Metformin With Additional 28-week Open-label Treatment to Evaluate the Safety in T2DM Subjects

This study evaluates the efficacy and safety and population PK of HMS5552 add-on to Metformin in adult type 2 diabetic subjects. There will be 2 groups in the first 24 weeks, one group will receive HMS5552 plus Metformin, while the other group will receive placebo plus Metformin; after 24 weeks, all subjects will receive HMS5552 plus Metformin for 28 weeks.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: HMS5552; Drug: Placebo

Detailed Description

This study is a phase III study in subjects with T2DM. As designed, the study will start with a 4-week, single-blind, placebo run-in period based on diet and exercise interventions for screening eligible subjects, meanwhile, subjects are treated with Metformin (Glucophage) at 1500mg/day as basic therapy throughout the treatment period. 3 weeks after run-in, eligibility is confirmed with required laboratory tests at -5±2 days prior to randomization. The eligible subjects are randomly assigned to HMS5552 75mg BID group or placebo BID group with ratio 1:1 to receive a 24-week double-blind treatment. Then all subjects receive 28-week open-label treatment of HMS5552 75mg BID add-on to Metformin. After 52-week treatment, all investigational drugs should be discontinued, followed by 1 week for safety evaluation. The dosage of Metformin (Glucophage) should be maintained at 1500 mg/day from run-in period to treatment completion.

• Study Type: Interventional
• Enrollment (Actual): 767
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Hua Medicine Limited

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:

1. Male or female, aged 18~75 years old;
2. T2DM and treated with Metformin ≥ 1500mg/day constantly for at least 12 consecutive weeks;
3. 7.5% ≤ HbA1c ≤ 10.0% at screening;
4. 18.5 kg/m2 < BMI < 35.0 kg/m2 at screening;

Exclusion Criteria:

1. Any anti-diabetic therapy other than Metformin within 12 weeks before screening;
2. Received insulin therapy more than 30 days within 1 year before screening;
3. Fasting C-peptide <0.81 ng/ml (0.27 nmol/L) at screening;
4. Medical history of severe hypoglycemia or frequent hypoglycemia, diabetic ketoacidosis, diabetes lactic acidosis or hyperosmotic nonketotic diabetic coma, severe cardio-cerebrovascular, unstable or rapidly progressive kidney disease, active liver diseases, diagnosed mental disease etc.
5. T1DM;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: HMS5552; 75mg BID	Drug: HMS5552; BID oral administration; Other Names: Glucokinase Activator (GKA)
PLACEBO_COMPARATOR: Placebo; BID	Drug: Placebo; BID oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in HbA1c	The change of HbA1c from baseline by comparing HMS5552 75 mg BID in combination with Metformin with Placebo BID in combination with Metformin in T2DM subjects after 24-week double-blind treatment	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events over time	including incidence of adverse events, incidence of hypoglycemic events, physical examination, vital signs, 12-lead ECG, clinical laboratory examinations (routine blood test, blood biochemistry and routine urine test).	52 weeks
The change of 2-hour postprandial plasma glucose (2h-PPG) from baseline	The change of 2-hour postprandial plasma glucose (2h-PPG) from baseline by comparing HMS5552 75 mg BID in combination with Metformin with Placebo BID in combination with Metformin in T2DM subjects after 24-week double-blind treatment	24 weeks
The change of fasting plasma glucose (FPG) from baseline	The change of fasting plasma glucose (FPG) from baseline by comparing HMS5552 75 mg BID in combination with Metformin with Placebo BID in combination with Metformin in T2DM subjects after 24-week double-blind treatment	24 weeks
The proportion of subjects with HbA1c < 7.0%	HbA1c response rate by comparing HMS5552 75 mg BID in combination with Metformin with Placebo BID in combination with Metformin in T2DM subjects after 24-week double-blind treatment	24 weeks
The change of HbA1c from baseline at each visit over time, except at Week 24	The change of HbA1c from baseline by comparing HMS5552 75 mg BID in combination with Metformin with Placebo BID in combination with Metformin in T2DM subjects at each visit over time, except at Week 24	24 weeks

Collaborators and Investigators

• Sponsor: Hua Medicine Limited
• Collaborators: Covance

Publications and helpful links

General Publications

• Yang W, Zhu D, Gan S, Dong X, Su J, Li W, Jiang H, Zhao W, Yao M, Song W, Lu Y, Zhang X, Li H, Wang G, Qiu W, Yuan G, Ma J, Li W, Li Z, Wang X, Zeng J, Yang Z, Liu J, Liang Y, Lu S, Zhang H, Liu H, Liu P, Fan K, Jiang X, Li Y, Su Q, Ning T, Tan H, An Z, Jiang Z, Liu L, Zhou Z, Zhang Q, Li X, Shan Z, Xue Y, Mao H, Shi L, Ye S, Zhang X, Sun J, Li P, Yang T, Li F, Lin J, Zhang Z, Zhao Y, Li R, Guo X, Yao Q, Lu W, Qu S, Li H, Tan L, Wang W, Yao Y, Chen D, Li Y, Gao J, Hu W, Fei X, Wu T, Dong S, Jin W, Li C, Zhao D, Feng B, Zhao Y, Zhang Y, Li X, Chen L. Dorzagliatin add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 3 trial. Nat Med. 2022 May;28(5):974-981. doi: 10.1038/s41591-022-01803-5. Epub 2022 May 12.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 15, 2017
• Primary Completion (ACTUAL): February 28, 2021
• Study Completion (ACTUAL): February 28, 2021

Study Registration Dates

• First Submitted: April 28, 2017
• First Submitted That Met QC Criteria: May 2, 2017
• First Posted (ACTUAL): May 4, 2017

Study Record Updates

• Last Update Posted (ACTUAL): August 26, 2021
• Last Update Submitted That Met QC Criteria: August 24, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Metformin; T2DM; GKA; HMS5552; Add-on therapy
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: HMM0302

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