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

Sponsor

Hua Medicine Limited (Industry)

Overall Status

Completed

CT.gov ID

NCT03141073

Collaborator

Covance (Industry)

767

Enrollment

Location

Arms

40.5

Actual Duration (Months)

18.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: HMS5552 Drug: Placebo	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

767 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 15, 2017

Actual Primary Completion Date :

Feb 28, 2021

Actual Study Completion Date :

Feb 28, 2021

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Change from baseline in HbA1c [24 weeks]
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

Secondary Outcome Measures

The change of 2-hour postprandial plasma glucose (2h-PPG) from baseline [24 weeks]
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
The change of fasting plasma glucose (FPG) from baseline [24 weeks]
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
The proportion of subjects with HbA1c < 7.0% [24 weeks]
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
The change of HbA1c from baseline at each visit over time, except at Week 24 [24 weeks]
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
Incidence of Treatment-Emergent Adverse Events over time [52 weeks]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

Any anti-diabetic therapy other than Metformin within 12 weeks before screening;
Received insulin therapy more than 30 days within 1 year before screening;
Fasting C-peptide <0.81 ng/ml (0.27 nmol/L) at screening;
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.
T1DM;