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

Phase 3

Completed

• Conditions: Diabetes Mellitus, Type 2
• Interventions: Drug: Placebo; Drug: HMS5552

• Registration Number: NCT03141073
• Lead Sponsor: Hua Medicine Limited

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.

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 Timeline

• Study First Submitted: 2017-04-28
• Study First Submitted QC: 2017-05-02
• Study First Posted: 2017-05-04
• Study Start: 2017-10-15
• Status Verified: 2021-02
• Primary Completion: 2021-02-28
• Study Completion: 2021-02-28
• Last Update Submitted: 2021-08-24
• Last Update Posted: 2021-08-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 767

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	BID
HMS5552	HMS5552	75mg BID

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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).
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

Trial Locations

Locations (1)

Hua Medicine Limited; 🇨🇳 Shanghai, China