Clinical trial NCT03141073: Long-term Efficacy and Safety of HMS5552 add-on to Metformin in T2DM Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Keywords: GKA
T2DM
HMS5552
Add-on therapy
Metformin
Lead sponsor: Hua Medicine Limited
Sponsor class: INDUSTRY
Collaborators: name: Covance
First posted: 2017-05-04
Enrollment: 767
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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;

Primary outcomes:
measure: Change from baseline in HbA1c
timeFrame: 24 weeks
Secondary outcomes:
measure: The change of 2-hour postprandial plasma glucose (2h-PPG) from baseline
timeFrame: 24 weeks
measure: The change of fasting plasma glucose (FPG) from baseline
timeFrame: 24 weeks
measure: The proportion of subjects with HbA1c < 7.0%
timeFrame: 24 weeks
measure: The change of HbA1c from baseline at each visit over time, except at Week 24
timeFrame: 24 weeks
measure: Incidence of Treatment-Emergent Adverse Events over time
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Hua Medicine Limited
Study officials:
affiliation: China-Japan Friendship Hospital
name: Wenying Yang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.