To Compare the Pharmacodynamics, Pharmacokinetics, Safety, and Tolerability Between SHR-3167 Injection and Glargine Insulin in Healthy Subjects

A Phase I Clinical Trial of the Pharmacodynamics, Pharmacokinetics, Safety, and Tolerability of a Single Subcutaneous Injection of SHR-3167 Injection and Glargine Insulin in Healthy Subjects

The purpose of this study is to compare the pharmacodynamic profile of a single subcutaneous dose of SHR-3167 injection versus insulin glargine U100 in healthy subjects.

Inclusion Criteria:

1. Voluntarily participate in the trial and sign the informed consent form; as judged by the researcher, the subjects are willing and able to adhere to all trial requirements and restrictions.
2. Healthy males, aged 18-55 years (inclusive).
3. Body mass index (BMI) within the range of 19.0-24.0 kg/m2 (inclusive); weight ≥50 kg.
4. Venous fasting blood glucose, oral glucose tolerance test (OGTT) 0 h venous glucose <6.1 mmol/L and >3.9 mmol/L; OGTT 2 h blood glucose <7.8 mmol/L; insulin release test (IRT) results are normal, or abnormal but judged by the researcher to have no clinical significance; glycated hemoglobin ≤6.0%.
5. No clinically significant history of past and/or present abnormalities in the heart, liver, kidneys, digestive system, nervous system, respiratory system, mental health, and metabolic conditions, as judged by the researcher; vital signs, physical examination, electrocardiogram, laboratory tests, and chest X-rays show no abnormalities or abnormalities deemed clinically insignificant (as determined by a clinical physician).
6. Agree to use effective contraception from the time of signing the informed consent form until 6 months after the last dose of the investigational drug, and to refrain from donating sperm during this period.
7. The researcher judges that the skin at the intended injection site of the investigational drug on the abdominal wall is normal, without fat hypertrophy, skin depressions, skin indurations, scars, inflammation, edema, ulcers, infections, bleeding, or any other condition that may affect the administration of the investigational drug to the subjects.
8. Capable of good communication with the researcher and able to comply with the trial requirements to complete the study

Exclusion Criteria:

1. History of diabetes or a first-degree relative with a history of diabetes.
2. History of hypokalemia, orthostatic hypotension, syncope, blackout, or severe hypoglycemic episodes.
3. Conditions judged by the investigator to potentially affect drug absorption, distribution, metabolism, excretion, safety assessment, or compliance, or if the investigator believes that participation in the trial poses a safety risk to the subject.
4. History of poorly controlled acute or chronic respiratory diseases in the 6 months prior to screening, including but not limited to chronic obstructive pulmonary disease (COPD), severe asthma, severe pneumonia, severe or critical COVID-19, active pulmonary tuberculosis.
5. Underwent any major surgery in the 6 months prior to screening or planned elective surgery during or within 1 month after dosing. Major surgery is defined as surgery that results in significant tissue trauma to organs within the skull, chest, abdomen, pelvis, or limbs and requires long-term recovery (e.g., organ transplantation, cardiac surgery, or joint replacement).
6. Donated blood (including blood components) or experienced blood loss exceeding 400mL in the 3 months prior to screening, or received a blood transfusion or blood products.
7. History of severe hypersensitivity reactions or known allergy to the investigational drug, its excipients, insulin, or insulin analogs.
8. History of drug abuse in the 12 months prior to screening or a positive result on a prohibited substance urine test.
9. Participated in any approved or unapproved clinical trial of investigational drugs/devices in the 90 days prior to screening, or planned to participate in another clinical trial during or within 1 month after the trial period.
10. Positive test results for human immunodeficiency virus antigen/antibody (HIV), hepatitis B virus surface antigen (HBsAg), hepatitis C virus antibody (anti-HCV), or Treponema pallidum antibody (TP).
11. Persons who have had an acute illness during the screening period.
12. Persons who have regularly consumed alcohol in the six months prior to screening (consuming more than 14 units of alcohol per week, with 1 unit approximately equal to 360mL of beer, 45mL of 40% alcohol spirit, or 150mL of wine); or those who have had a positive alcohol breath test at baseline or are unwilling to abstain from alcohol during the trial.
13. Persons who have smoked an average of more than 5 cigarettes per day in the three months prior to screening, or are unwilling to quit smoking before the completion of all glucose clamp tests.
14. Persons who have used any prescription drugs, traditional Chinese medicine, herbal medicine, or over-the-counter drugs, supplements, or have received any vaccinations in the four weeks prior to dosing.
15. Persons who have taken any medications affecting insulin lowering in the 28 days prior to screening (e.g., corticosteroids, diuretics, adrenaline, salbutamol, glucagon, growth hormone, thyroxine, etc.).
16. Persons who have consumed excessive tea, coffee, or caffeine-containing beverages (≥8 cups, with 1 cup = 250mL) daily in the two weeks prior to dosing, or do not agree to abstain from consuming grapefruit juice or any foods and beverages containing alcohol and xanthine (including chocolate, tea, coffee, cola, etc.) for 48 hours before dosing and until the completion of all glucose clamp tests.
17. Persons who have made significant changes in diet or exercise habits in the three months prior to screening, such as weight loss or intense exercise.
18. Persons who are unwilling or unable to follow the lifestyle guidance described in the trial protocol, have special dietary requirements, or cannot adhere to a standardized diet.
19. Persons who cannot tolerate venipuncture, have difficulty with blood sampling, have a history of fainting or fainting at the sight of needles, or cannot establish a venous route in both upper limbs.
20. Persons who are directly involved in this trial as staff of the research center or sponsor, or their immediate relatives (spouse, parents/legal guardians, siblings, or children).
21. Other conditions that the researcher deems unsuitable for the participant to take part in this trial.