A Study of Efficacy and Safety of Supaglutide in Type 2 Diabetes Patients On Metformin Treatment(SUPER-2)
- Conditions
- Type2 Diabetes
- Interventions
- Biological: supaglutide injection+metforminOther: placebo+metformin
- Registration Number
- NCT04998032
- Lead Sponsor
- Shanghai Yinnuo Pharmaceutical Technology Co., Ltd.
- Brief Summary
This is a study to evaluate the efficacy and safety of Supaglutide injection in the treatment of type 2 diabetes patients with poor glycemic control after metformin treatment.
This trial includes dosage determination (Phase IIb) and efficacy confirmation stage(Phase III ). The primary outcome of the phase IIb period is to preliminarily evaluate the efficacy and safety of Supaglutide combined with metformin and to provide the recommended dosage for the Phase 3 period after 12-week treatment.
The primary outcome of the Phase III period is to evaluate the efficacy and safety of Supaglutide combined with metformin treatment after 24-week, double-blind treatment. The secondary outcome is to evaluate the efficacy and safety of Supaglutide combined with metformin during the 24-week, double-blinded plus 28-week, open-label treatment period.
- Detailed Description
This trial includes a 2-week screening period, a 4-week metformin titration and dose-stabilization period, a 4-week induction period, a 24-week double-blind treatment period and a 28-week open-label treatment period, followed by a 4-week follow-up period and a follow-up visit. We calculated that the sample size would need to be 632, including 120 subjects in the period of Phase IIb and 512 subjects in the period of Phase III. During the phase IIb period, subjects were randomly assigned to once-weekly subcutaneously injected Supaglutide 1mg plus metformin, 3mg plus metformin and placebo plus metformin at a ratio of 1:1:1.
When the number of participants who have completed the 12-week follow up reached 120, interim analyses will be performed and the results will be evaluated by Independent Data Monitoring Committee experts to determine the recommended phase 3 dosage.
During the phase III stage, subjects were randomly assigned 1:1 to the "recommended phase 3 dosage + metformin" group and the "placebo + metformin" group.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 620
-
Male or female patients aged from 18 to 75;
-
Clinical diagnosed of Type 2 diabetes for at least 8 weeks ，receive metformin single treatment ；
-
During screening, HbA1c: 7.5% ≤ HbA1c ≤ 11% ，and before randomization 7.5% ≤ HbA1c ≤ 10.5%;
-
During screening and before randomization: FPG< 13.9 mmol/L； 5.18.5 kg/m2 ≤ BMI ≤ 35 kg/m2;
-
without birth plan and voluntarily take effective contraceptive measures; 7. fully understood the study, signed the informed consent；
- Diabetes other than Type 2;
- Any dipeptidyl peptidase IV and / or glucagon-like peptide-1 （GLP-1）analogues were used within 3 months before screening;
- Continuous use of insulin for more than 14 days in the previous year;
- C-Peptide <0.3 nmol/L;
- Diabetic ketoacidosis, diabetic lactic acidosis or hyperosmolar non ketonic diabetic coma occurred within 6 months before screening;
- Unstable proliferative retinopathy or macular lesion, severe diabetic neuropathy, intermittent claudication or diabetic foot occurred within 6 months before screening;
- Severe hypoglycemia occurred within 6 months before screening
- Severe trauma infection or operation within one month before screening;
- Blood donation or massive blood loss or transfusion within 3 months ;
- Suspected active infection ;
- Growth hormone therapy was performed within 6 months before screening;
- Patients having received corticosteroid continuous ≥ 7 days through within 2 months ;
- use any drugs or surgery with weight control effect within 2 months;
- weight change of more than 5% within 3 months;
- mean systolic pressure (SBP) ≥ 160mmhg and / or diastolic pressure （DBP） ≥ 90 mmHg at screening, or new/changed antihypertensive drugs or adjusted dosage of antihypertensive drugs within 4 weeks before screening or before induction period
- with a history of severe cardiovascular disease, high risk of stroke/stroke within 6 months before screening;
- with a history of acute or chronic pancreatitis, symptomatic gallbladder , pancreatic injury and other risk factors for pancreatitis, or with blood amylase and/or blood lipase ≥1.5 times the upper limit of normal (ULN) at the time of screening or before randomization;
- Calcitonin level ≥50 ng/L (pg/mL) during screening;
- with a history of medullary thyroid cancer, multiple endocrine neoplasm (Men) 2A or 2B syndrome, or related family history;
- with clinically significant abnormal gastric emptying , severe chronic gastrointestinal diseases , long-term use of drugs that have a direct impact on gastrointestinal peristalsis , or having undergone gastrointestinal surgery within 6 months before screening, are not suitable to participate in this clinical study according to the evaluation of the researchers;
- suffering from hematological diseases or any disease causing hemolysis or erythrocyte instability ;
- Uncontrolled hyperthyroidism or hypothyroidism;
- with hemoglobinopathy that may affect the determination of HbA1c levels;
- HBsAg, Hepatitis C antibody, HIV-Ab, Treponema pallidum antibody or Corona Virus Disease 2019 nucleic acid tested positive;
- serious mental illness;
- drinking more than 14 standard units weekly within 6 months before screening ;
- a history of organ transplantation or other acquired or congenital immune system diseases;
- allergic to the active ingredients (GLP-1 and GLP-1 analogues) of the study drug;
- clear contraindications for the use of metformin;
- clear contraindications for Empagliflozin；
- Any of the following conditions: the pacemaker was installed when screened; no pacemaker was installed, but 12 lead ECG showed degree II or III atrioventricular block, long QT syndrome or QTc interval ≥ 450ms ; Patients with New York Heart Function Classification III or IV; Or other abnormal cardiac function with clinical significance that is not suitable for clinical research judged by researchers;
- acute or chronic hepatitis, or whose laboratory examination indexes meet one of the following criteria at the time of screening or before randomization : alanine aminotransferase (ALT) level ≥ 2.5 fold ULN, aspartate aminotransferase (AST) ≥ 2.5 fold ULN, fasting triglyceride (TG) > 5.7 mmol/L or 500 mg/dl; the glomerular filtration rate (EGFR) < 60 ml/min/1.73 square meters was calculated by CKD-EPI (epi - (SCR)) formula;
- participated in clinical trials of other drugs or devices within 3 months before screening;
- Medication compliance in the metformin dosage stable period was < 80% or > 120%;
- Supaglutide placebo injection compliance during the induction period was <75% or>125%, or metformin compliance <80% or >120%;
- Any other situation that researchers think may affect the patients' informed consent or compliance with the trial protocol;
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description supaglutide RP3D dose+metformin supaglutide injection+metformin Supaglutide Subcutaneous injection once a week for 52weeks,combined with metformin placebo+metformin placebo+metformin Placebo Subcutaneous injection once a week for 52weeks,,combined with metformin
- Primary Outcome Measures
Name Time Method HbA1c 12 weeks for phase IIb; 24weeks and 52 weeks for phase III The change in mean HbA1c concentrations (%)from baseline with Supaglutide versus placebo
- Secondary Outcome Measures
Name Time Method Area under the curve of C-peptide 12 weeks for phase IIb; 24weeks and 52 weeks for phase III Area under the curve of C-peptide (AUC0-120min,nmol/L) during the MMTT
salvage treatment 12 weeks for phase IIb; 24weeks and 52 weeks for phase III Percentage of subjects receiving salvage treatment(%)
HbA1c<7.0% and <6.5% 12 weeks for phase IIb; 24weeks and 52 weeks for phase III The proportion of participants who achieved HbA1c target (HbA1c\<7.0% and \<6.5% Patient percentage)
Fasting insulin 12 weeks for phase IIb; 24weeks and 52 weeks for phase III Fasting insulin changes（pmol/L) relative to baseline
fasting C-peptide 12 weeks for phase IIb; 24weeks and 52 weeks for phase III Fasting C-peptide changes (nmol/L) relative to baseline
Area under the curve of insulin 12 weeks for phase IIb; 24weeks and 52 weeks for phase III Area under the curve of insulin (AUC0-120min,pmol/L) during the MMTT
fasting glucagon 12 weeks for phase IIb; 24weeks and 52 weeks for phase III fasting glucagon changes (pg/ml) relative to baseline
fasting plasma glucose 12 weeks for phase IIb; 24weeks and 52 weeks for phase III Changes in fasting plasma glucose (mmol/L) relative to baseline
Area under the curve of blood glucose 12 weeks for phase IIb; 24weeks and 52 weeks for phase III Area under the curve of blood glucose (AUC0-120min,mmol/L) during the multi-maneuvering target tracking
Total cholesterol 12 weeks for phase IIb; 24weeks and 52 weeks for phase III Changes in total cholesterol (mmol/L) relative to baseline
low density lipoprotein 12 weeks for phase IIb; 24weeks and 52 weeks for phase III Changes in low density lipoprotein (mmol/L) relative to baseline
High density lipoprotein 12 weeks for phase IIb; 24weeks and 52 weeks for phase III Changes in high density lipoprotein (mmol/L) relative to baseline
triglyceride 12 weeks for phase IIb; 24weeks and 52 weeks for phase III Changes in triglyceride(mmol/L) relative to baseline
weight 12 weeks for phase IIb; 24weeks and 52 weeks for phase III Weight change from baseline(kg)
Trial Locations
- Locations (61)
Jiangxi Provincial People's Hospital
🇨🇳Nanchang, China
Nanjing First Hospital
🇨🇳Nanjing, China
Nanjing Jiangning Hospital
🇨🇳Nanjing, China
Sir Run Run Hospital of Nanjing Medical University
🇨🇳Nanjing, China
Nanyang First People's Hospital
🇨🇳Nanyang, China
Nanyang Second General Hospital
🇨🇳Nanyang, China
The First Affiliated Hospital of Nanyang Medical College
🇨🇳Nanyang, China
Puyang Oilfield General Hospital
🇨🇳Puyang, China
The First Hospital of Qinhuangdao
🇨🇳Qinhuangdao, China
The First Hospital of Qiqihar
🇨🇳Qiqihar, China
Changhai Hospital
🇨🇳Shanghai, China
Huadong Hospital
🇨🇳Shanghai, China
Shanghai Pudong New Area People's Hospital
🇨🇳Shanghai, China
Shanghai Sixth People's Hospital Affiliated to Shanghai JiaoTong University
🇨🇳Shanghai, China
Shanghai Tongren Hospital
🇨🇳Shanghai, China
Siping Central Hospital
🇨🇳Siping, China
Second Hospital of Shanxi Medical University
🇨🇳Taiyuan, China
The Second Affiliated Hospital of Shandong First Medical University
🇨🇳Tanan, China
Tianjin Medical University General Hospital
🇨🇳Tianjing, China
The Second Hospital of Tanjin Medical University
🇨🇳Tianjin, China
Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
🇨🇳Wuhan, China
Jiangyin People's Hospital
🇨🇳Wuxi, China
The Affiliated Hospital of Xuzhou Medical University
🇨🇳Xuzhou, China
Xuzhou Cancer Hospital
🇨🇳Xuzhou, China
The Second People's Hospital of Yibin
🇨🇳Yibin, China
Yichun People's Hospital
🇨🇳Yichun, China
Yiyang Central Hospital
🇨🇳Yiyang, China
The Second Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, China
First People's Hospital of Zunyi
🇨🇳Zunyi, China
Handan First Hospital
🇨🇳Handan, China
The Fourth Affiliated Hospital of Harbin Medical University
🇨🇳Harbin, China
Heze Municipal Hospital
🇨🇳Heze, China
Huai'an First People's Hospital
🇨🇳Huai'an, China
Huizhou Central Hospital
🇨🇳Huizhou, China
Jilin People's Hospital
🇨🇳Jilin, China
Huai'an Second People's Hospital
🇨🇳Huai'an, China
Jinan Central Hospital Affiliated to Shandong First Medical University
🇨🇳Jinan, China
Jincheng General Hospital
🇨🇳Jincheng, China
Jingzhou Central Hospital
🇨🇳Jingzhou, China
The Second Affiliated Hospital of Kunming Medical University
🇨🇳Kunming, China
The Second People's Hospital of Lianyungang
🇨🇳Lianyungang, China
Linfen People's Hospital
🇨🇳Linfen, China
First People's Hospital of Tancheng
🇨🇳Linyi, China
Liuzhou People's Hospital
🇨🇳Liuzhou, China
The First Affiliated Hospital of Henan University
🇨🇳Luoyang, China
Meihekou Central Hospital
🇨🇳Meihekou, China
Beijing Boai Hospital
🇨🇳Beijing, China
Beijing Pinggu Hospital
🇨🇳Beijing, China
Emergency General Hospital
🇨🇳Beijing, China
Cangzhou Central Hospital
🇨🇳Cangzhou, China
Cangzhou Hospital of Integrated TCM-WM Hebei
🇨🇳Cangzhou, China
The Second Hospital of Jilin University
🇨🇳Changchun, China
First People's Hospital of Changde
🇨🇳Changde, China
Changsha Hopital Affiliated to Hunan University
🇨🇳Changsha, China
The Fourth Hospital of Changsha
🇨🇳Changsha, China
Chengdu Fifth People's Hospital
🇨🇳Chengdu, China
Chenzhou First People's Hospital
🇨🇳Chenzhou, China
Chongqing Ninth People's Hospital
🇨🇳Chongqing, China
Dalian Municipal Central Hospital
🇨🇳Dalian, China
Daqing People's Hospital
🇨🇳Daqing, China
Jilin Guowen Hospital
🇨🇳Gongzhuling, China