A Study of Efficacy and Safety of Supaglutide in Type 2 Diabetes Patients On Metformin Treatment

Type2 Diabetes Clinical Trial

Official title:

Efficacy and Safety of Once-weekly Supaglutide Versus Placebo in Patients With Type 2 Diabetes Suboptimally Controlled on Metformin: A Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04998032
• Other study ID #: YN011-302
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: October 12, 2021
• Est. completion date: August 28, 2023

Study information

• Verified date: January 2023
• Source: Shanghai Yinnuo Pharmaceutical Technology Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 620
• Est. completion date: August 28, 2023
• Est. primary completion date: July 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Male or female patients aged from 18 to 75;

2. Clinical diagnosed of Type 2 diabetes for at least 8 weeks ,receive metformin single treatment ;

3. During screening, HbA1c: 7.5% = HbA1c = 11% ,and before randomization 7.5% = HbA1c = 10.5%;

4. During screening and before randomization: FPG< 13.9 mmol/L; 5.18.5 kg/m2 = BMI = 35 kg/m2;

6. without birth plan and voluntarily take effective contraceptive measures; 7. fully understood the study, signed the informed consent;

Exclusion Criteria:

1. Diabetes other than Type 2;

2. Any dipeptidyl peptidase IV and / or glucagon-like peptide-1 (GLP-1)analogues were used within 3 months before screening;

3. Continuous use of insulin for more than 14 days in the previous year;

4. C-Peptide <0.3 nmol/L;

5. Diabetic ketoacidosis, diabetic lactic acidosis or hyperosmolar non ketonic diabetic coma occurred within 6 months before screening;

6. Unstable proliferative retinopathy or macular lesion, severe diabetic neuropathy, intermittent claudication or diabetic foot occurred within 6 months before screening;

7. Severe hypoglycemia occurred within 6 months before screening

8. Severe trauma infection or operation within one month before screening;

9. Blood donation or massive blood loss or transfusion within 3 months ;

10. Suspected active infection ;

11. Growth hormone therapy was performed within 6 months before screening;

12. Patients having received corticosteroid continuous = 7 days through within 2 months ;

13. use any drugs or surgery with weight control effect within 2 months;

14. weight change of more than 5% within 3 months;

15. 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

16. with a history of severe cardiovascular disease, high risk of stroke/stroke within 6 months before screening;

17. 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;

18. Calcitonin level =50 ng/L (pg/mL) during screening;

19. with a history of medullary thyroid cancer, multiple endocrine neoplasm (Men) 2A or 2B syndrome, or related family history;

20. 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;

21. suffering from hematological diseases or any disease causing hemolysis or erythrocyte instability ;

22. Uncontrolled hyperthyroidism or hypothyroidism;

23. with hemoglobinopathy that may affect the determination of HbA1c levels;

24. HBsAg, Hepatitis C antibody, HIV-Ab, Treponema pallidum antibody or Corona Virus Disease 2019 nucleic acid tested positive;

25. serious mental illness;

26. drinking more than 14 standard units weekly within 6 months before screening ;

27. a history of organ transplantation or other acquired or congenital immune system diseases;

28. allergic to the active ingredients (GLP-1 and GLP-1 analogues) of the study drug;

29. clear contraindications for the use of metformin;

30. clear contraindications for Empagliflozin;

31. 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;

32. 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;

33. participated in clinical trials of other drugs or devices within 3 months before screening;

34. Medication compliance in the metformin dosage stable period was < 80% or > 120%;

35. Supaglutide placebo injection compliance during the induction period was <75% or>125%, or metformin compliance <80% or >120%;

36. Any other situation that researchers think may affect the patients' informed consent or compliance with the trial protocol;

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type2 Diabetes

Intervention

Biological:
• supaglutide injection+metformin
supaglutide subcutaneous injection under RP3D dose combined with metformin treatment

Other:
• placebo+metformin
placebo subcutaneous injection combined with metformin treatment

Locations

Country	Name	City	State
China	Tianjin medical university general hospital	Tianjin	Hebei

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Yinnuo Pharmaceutical Technology Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HbA1c	The change in mean HbA1c concentrations (%)from baseline with Supaglutide versus placebo	12 weeks for phase IIb; 24weeks and 52 weeks for phase III
Secondary	fasting plasma glucose	Changes in fasting plasma glucose (mmol/L) relative to baseline	12 weeks for phase IIb; 24weeks and 52 weeks for phase III
Secondary	HbA1c<7.0% and <6.5%	The proportion of participants who achieved HbA1c target (HbA1c<7.0% and <6.5% Patient percentage)	12 weeks for phase IIb; 24weeks and 52 weeks for phase III
Secondary	Fasting insulin	Fasting insulin changes(pmol/L) relative to baseline	12 weeks for phase IIb; 24weeks and 52 weeks for phase III
Secondary	fasting C-peptide	Fasting C-peptide changes (nmol/L) relative to baseline	12 weeks for phase IIb; 24weeks and 52 weeks for phase III
Secondary	fasting glucagon	fasting glucagon changes (pg/ml) relative to baseline	12 weeks for phase IIb; 24weeks and 52 weeks for phase III
Secondary	Area under the curve of blood glucose	Area under the curve of blood glucose (AUC0-120min,mmol/L) during the multi-maneuvering target tracking	12 weeks for phase IIb; 24weeks and 52 weeks for phase III
Secondary	Area under the curve of insulin	Area under the curve of insulin (AUC0-120min,pmol/L) during the MMTT	12 weeks for phase IIb; 24weeks and 52 weeks for phase III
Secondary	Area under the curve of C-peptide	Area under the curve of C-peptide (AUC0-120min,nmol/L) during the MMTT	12 weeks for phase IIb; 24weeks and 52 weeks for phase III
Secondary	Total cholesterol	Changes in total cholesterol (mmol/L) relative to baseline	12 weeks for phase IIb; 24weeks and 52 weeks for phase III
Secondary	low density lipoprotein	Changes in low density lipoprotein (mmol/L) relative to baseline	12 weeks for phase IIb; 24weeks and 52 weeks for phase III
Secondary	High density lipoprotein	Changes in high density lipoprotein (mmol/L) relative to baseline	12 weeks for phase IIb; 24weeks and 52 weeks for phase III
Secondary	triglyceride	Changes in triglyceride(mmol/L) relative to baseline	12 weeks for phase IIb; 24weeks and 52 weeks for phase III
Secondary	weight	Weight change from baseline(kg)	12 weeks for phase IIb; 24weeks and 52 weeks for phase III
Secondary	salvage treatment	Percentage of subjects receiving salvage treatment(%)	12 weeks for phase IIb; 24weeks and 52 weeks for phase III