Comparative Clinical Trial of Pharmacokinetics and Pharmacodynamics of Human Insulin Injection

A Single-Center, Randomized, Double-Blind, Two-Formulation, Single-Dose, Two-Period Crossover Clinical Trial Comparing Pharmacokinetics and Pharmacodynamics of Human Insulin Injection

A study of Clinical Trial Comparing Pharmacokinetics and Pharmacodynamics of Human Insulin Injection,in Wuhan Pulmonary Hospital (Wuhan Tuberculosis Prevention and Control Institute).To compare the pharmacokinetic and pharmacodynamics properties of a single subcutaneous dose of the human insulin injection (USLIN®R, Zhuhai United Laboratories (Zhongshan) Co., Ltd.) with the reference product (Novolin®R, Novo Nordisk Inc.) in healthy male subjects,and to evaluate the safety, tolerability, and immunogenicity of the test formulation versus the reference formulation in healthy male subjects.This single-center, randomized, double-blind, two-formulation, single-dose, two-period crossover study will enroll 32 healthy male subjects randomized 1:1 into two sequence groups (A/B, group A is administered in the sequence of T-R, while group B is in R-T). To evaluate the pharmacokinetic and pharmacodynamic properties of the test preparation and the control preparation in healthy male subjects. Each subject will receive single doses of both test and reference formulations across two periods (with ≥14-day washout), following the predefined sequence allocation table. After completing period 2 pharmacokinetic blood sampling, subjects will administer assigned insulin TID for two consecutive days to assess test-reference immunogenicity differences.

Inclusion Criteria:

1. Age: 18 to 55 years old (inclusive of 18 and 55 years).
2. Gender: Male.
3. Body Weight: Not less than 55.0 kg for men, with a body mass index [BMI = weight (kg) / height² (m²)] between 18.0 and 29.0 kg/m² (inclusive of boundary values).
4. Vital Signs: Systolic blood pressure ≥90 mmHg and <140 mmHg, diastolic blood pressure ≥60 mmHg and <90 mmHg, pulse rate ≥60 beats/min and ≤100 beats/min, body temperature (forehead) between 36.0°C and 37.3°C, with final judgment by the investigator.
5. Glucose Tolerance: Normal glucose tolerance (fasting plasma glucose (FPG) <6.10 mmol/L and >3.50 mmol/L, and 2-hour postprandial blood glucose in oral glucose tolerance test (OGTT) <140 mg/dL (7.78 mmol/L)), glycated hemoglobin value <6.3% and >4.5%.

Exclusion Criteria:

1. Those who have participated in a clinical trial of another drug/device and used the investigational drug/device within 6 months.
2. Those with clinically significant abnormal conditions requiring exclusion, including but not limited to neurological, cardiovascular, hematologic and lymphatic, immune, renal, hepatic, gastrointestinal, respiratory, metabolic, and skeletal system disorders, particularly those with a history of hypoglycemia, hypokalemia, postural hypotension, syncope or blackout, diabetes mellitus, or a family history (first-degree relatives) of diabetes mellitus.
3. Those with a history of severe vomiting, diarrhea, or any other disease or condition that could interfere with trial results within 7 days prior to the trial.
4. Those with a history of specific allergies (e.g., asthma, urticaria, eczema) or allergies to any medications, foods, or pollen, or known allergies to insulin.
5. Those with positive anti-insulin antibodies.
6. Those who have lost or donated more than 400 mL of blood, received blood transfusions, or used blood products within 3 months prior to the trial, or who plan to donate blood during the trial.
7. Subjects with plans for childbearing or sperm donation from 2 weeks prior to the trial to 6 months after the last dose, and who are unwilling or unable to use effective contraception.
8. Those with clinically significant abnormalities in general physical examination, laboratory tests (blood routine, blood biochemistry, coagulation function, urine routine, etc.) within 7 days prior to the trial, or electrocardiogram results deemed clinically significant by the clinician within 14 days prior to the trial.
9. Those with one or more clinically significant positive results for hepatitis B, hepatitis C, HIV, or syphilis tests.
10. Those who have undergone surgery within 3 months prior to the trial, plan to undergo surgery during the study, or have had surgery that affects drug absorption, distribution, metabolism, or excretion.
11. Those who consumed more than 14 units of alcohol per week within 3 months prior to the trial (1 unit = 17.7 mL ethanol, i.e., 354 mL of 5% alcohol beer, 44 mL of 40% alcohol liquor, or 147 mL of 12% alcohol wine), or those unable to abstain from alcohol during the trial.
12. Those who smoked an average of more than 5 cigarettes per day within 3 months prior to the trial, or those unable to stop using any tobacco-based or nicotine products (e.g., nicotine patches, chewing gums) during the trial.
13. Those who consumed excessive amounts of tea, coffee, and/or caffeine-rich beverages (more than 8 cups, 1 cup = 250 mL) per day within 3 months prior to the trial.
14. Those who consumed any food or beverage rich in caffeine/xanthine or other special ingredients (e.g., strong tea, coffee, chocolate, cola, animal offal, grapefruit, grapefruit juice, dragon fruit, mango) from screening to 2 days before admission, which, in the investigator's judgment, may affect drug absorption, distribution, metabolism, or excretion, or those unable to stop consuming such foods or beverages by the end of drug administration.
15. Those who used any drugs that alter liver enzyme activity within 28 days prior to the trial (common liver enzyme inducers: barbiturates (phenobarbital being the most common), carbamazepine, aminoglutethimide, griseofulvin, meprobamate, phenytoin, glutethimide, rifampicin, dexamethasone; common liver enzyme inhibitors: chlorpromazine, cimetidine, ciprofloxacin, metronidazole, chloramphenicol, sulfonamides).
16. Those who used any drugs affecting insulin's glucose-lowering effects within 28 days prior to the trial (e.g., corticosteroids, danazol, diazoxide, diuretics, epinephrine, salbutamol, terbutaline, glucagon, growth hormone, thyroid hormone, beta-blockers).
17. Those unable to eat, with swallowing difficulties, special dietary requirements, or unable to follow a standardized diet.
18. Those who used any prescription drugs, over-the-counter drugs, nutraceuticals, herbal products, or vaccines within 14 days prior to the trial.
19. Those engaged in hazardous mechanical operations, such as working at heights or driving motor vehicles.
20. Those unable to tolerate venipuncture or with a history of hemophobia or needle phobia.
21. Those with a history of asthma or seizures.
22. Those with a history of hereditary galactose intolerance, lactase deficiency, or glucose-galactose malabsorption.
23. ；Those who used any illicit drugs within one year prior to the trial.
24. Those with a positive alcohol breath test or positive drug abuse screening.
25. Subjects deemed by the investigator to have poor treatment compliance or any factors making participation in this trial inappropriate.