diabetes
Conditions
Interventions
ungrouped:This study is an Phase I clinical trial in patients with type 2 diabetes mellitus (T2DM) to evaluate the pharmacokinetics, pharmacodynamics, and safety of multiple subcutaneous injections of
the formal trial plans to enroll 50 subjects. Subjects participate in the screening to assess whether they meet the inclusion criteria. Subjects who meet the criteria enter the introduction period, wh
Sponsors
West China Hospital of Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 59 Years
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following criteria for enrollment in this study: 1. Before carrying out any activities related to this study, with my consent and signed an informed consent form, I am willing and able to follow the requirements of the trial protocol to complete this study; 2. On the day of signing the informed consent form, the age is 18~59 years old (including the cut-off value at both ends), and the gender is not limited; 3. Diagnosed with type 2 diabetes mellitus >=6 months; 4. With or without the following oral hypoglycemic drugs at screening, and meet the > of stable treatment = 3 months: 1) any metformin preparation; 2) dipeptidyl peptidase 4 (DPP-4) inhibitors; 3) sodium-glucose cotransporter 2 (SGLT2) inhibitors; 4) a-glycosidase inhibitors; 5) the combination of the above-mentioned oral drugs; Note: Stable treatment is defined as no change in the drug and total daily dose. 5. Current total daily basal insulin dose (insulin glargine U100 or U300, insulin degludec or insulin detemir) = 0.2 U/kg/day; 6. HbA1c <= 9% at screening; 7. Body mass index (BMI) of 18.0~32.5 kg/m^2 (including both ends) at screening; 8. Screening temporal C-peptide < 0.8 nmol/L; 9. Female subjects of childbearing potential and male subjects whose partner is a female of childbearing potential have no fertility plan and are willing to comply with contraceptive requirements in accordance with local regulations within 3 months after signing the informed consent form to the last dose, and have no plans to donate eggs/sperm; Female subjects of childbearing potential have a negative pregnancy test during the screening period and are not lactating.
Exclusion criteria
Exclusion criteria: Subjects who meet any of the following criteria will not be enrolled in this study: The following examination abnormalities are present at screening: 1. The laboratory examination meets any of the following conditions: 1) Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > = 2.5 times the upper limit of the normal range, or total bilirubin > = 1.5 times the upper limit of the normal range. 2) Estimated glomerular filtration rate (eGFR) =5.65 mmol/L (500 mg/dL). 5) Other laboratory examination abnormalities judged by the investigator that may affect the efficacy or safety assessment. 2. Poor blood pressure control (with or without antihypertensive therapy): systolic blood pressure >=160 mmHg, or diastolic blood pressure >=100 mmHg at screening. Presence of the following diseases or history prior to screening or enrollment: 3. Known or suspected allergy to investigational drugs or related products; or a history of multiple and/or severe allergies to medications or foods. 4. Diagnosed or suspected of type 1 diabetes, occult autoimmune diabetes, special type diabetes mellitus or secondary diabetes mellitus (monogenic diabetes syndrome, pancreatitis, drug- or chemical-induced diabetes). 5. Acute complications of diabetes mellitus (ketoacidosis or hyperosmolar hyperglycemic state, etc.) from 6 months before screening to enrollment; or, as judged by the investigator, >=1 severe hypoglycemia within 6 months prior to screening or recurrent hypoglycemic events within 1 month prior to screening (defined as >=4 hypoglycemic events within 1 month, i.e., blood glucose <3.9 mmol/L), or asymptomatic hypoglycemia. 6. Previous severe chronic complications of diabetes, or proliferative diabetic retinopathy, or uncontrolled and potentially unstable or requiring acute treatment of non-proliferative diabetic retinopathy or macular degeneration (confirmed by fundus photography or dilated fundoscopy within 3 months prior to screening or during the screening period). 7. History of severe cardiovascular and cerebrovascular disease attack from 6 months before screening to enrollment, including but not limited to heart failure (NYHA classification III~IV), myocardial infarction, unstable angina, stroke or transient ischemic attack, clinically significant arrhythmia or conduction disorder, or coronary artery bypass grafting or percutaneous coronary intervention, etc.; or an increased risk of thrombosis, such as an individual or a first-degree relative with a history of deep vein thrombosis. 8. Those who have serious infection, severe trauma, or have undergone large and medium-sized surgery within 1 month before screening, or plan to undergo surgery during the trial. 9. Positive test for hepatitis B surface antigen (HBsAg), HIV antibody, Treponema pallidum specific antibody or hepatitis C virus antibody; or the investigator judges that the subject is in the incubation or active period of the above infection. 10. Presence of acute or chronic hepatitis, cirrhosis, or other serious liver disease other than non-alcoholic fatty liver disease. 11. Have malignancy or a history of malignancy within 5 years prior to screening (excluding cured localized basal cell carcinoma of the skin, carcinoma in situ of the cervix and carcinoma in situ of the prostate), or have a high risk of cancer occurring/recurring. Use of any of the following medications or treatments prior to screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The AUC value of SHR-3167 reaching a steady state after multiple subcutaneous administrations; | — |
Secondary
| Measure | Time frame |
|---|---|
| SHR-3167 administered subcutaneously multiple times to reach steady-state AUCGIR, 0-30 hours, SS, AUCGIR, 96-132 hours, SS;Evaluation of the PD parameters of degludec insulin at steady state: AUCGIR, 0-24 hours, SS, GIRmax, 0-24 hours, SS;PK parameters for multiple subcutaneous administrations of SHR-3167 to reach steady state: including dose-standardized AUC SHR-3167, tau, ss, Cmax, SHR-3167, SS, dose-standardized Cmax, SHR-3167, SS, tmax, SHR-3167, ss, t1/2, SHR-3167, ss, Ctrough, CL/FSHR-3167, SS, VSS/FSHR-3167, SS;Evaluate the PK parameters of degludec insulin at the steady-state level, such as AUCDeg, tau, SS, dose-normalized AUCDeg, tau, SS, Cmax, Deg, SS, dose-normalized Cmax, Deg, SS, tmax, Deg, SS, and CDeg, trough;Adverse events, hypoglycemic events, laboratory tests, vital signs, physical examinations and electrocardiograms, etc.;Immunogenicity (antibody against SHR-3167); | — |
Countries
China
Contacts
Public ContactYerong Yu
West China Hospital of Sichuan University
Outcome results
None listed