Comparison of the Pharmacokinetics （PK）and Pharmacodynamics （PD）Biosimilarity of Insulin Aspart Injections After Single-Dose Subcutaneous Administration to Healthy Volunteers

Official title

Comparison of the Pharmacokinetics (PK) and Pharmacodynamics (PD) Biosimilarity of Insulin Aspart Injections After Single-Dose Subcutaneous Administration to Healthy Volunteers: A Single-Center, Randomized, Double-blinded, Two-Treatment, Two-period, Two-sequence Crossover Study

Overview

The present study is designed to compare the pharmacokinetic, pharmacodynamic and safety characteristics of UBLIN® (test product) and NovoRapid® (reference product) in healthy male participants. The treatment consists of one single dose of the test or reference product, administered during each of the two study periods, separated by 7 days between dosing. A total of 44 participants will be enrolled in this trial and randomized in a 1:1 ratio into two groups (A/B), stratified by race (Asian, non-Asian).

Interventions

• Drug Insulin Aspart Injection（UBLIN®）
  The dosage per cycle is 0.2 U/kg
• Drug Insulin Aspart Injection（NovoRapid®）
  The dosage per cycle is 0.2 U/kg

Primary outcome measures

• Area Under the Curve (AUC) of Insulin Aspart Plasma Concentration From Time 0 to the Time of Last Measurable Concentration, AUC0-t [Time frame: 0 to 10 hours]
• Peak Plasma Concentration of Insulin Aspart, Cmax [Time frame: 0 to 10 hours]
• Area Under The Curve (AUC) of Glucose Infusion Rate(GIR) From Time 0 To End Of Clamp At Time T, AUCGIR0-t [Time frame: 0 to 10 hours]
• Maximum Glucose Infusion Rate, GIRmax [Time frame: 0 to 10 hours]

Secondary outcome measures (9)

• Area Under the Curve (AUC) of Insulin Aspart Plasma Concentration From Time 0 to 2 Hours Post-Dose, AUC0-2h [Time frame: 0 to 2 hours]
• Area Under the Curve (AUC) of Insulin Aspart Plasma Concentration From 2 Hours Post-dose to the Time of Last Measurable Concentration, AUC2-t [Time frame: 2 to 10 hours]
• Time to Reach Peak Plasma Concentration of Insulin Aspart, Tmax [Time frame: 0 to 10 hours]
• Elimination Rate Constant, λz [Time frame: 0 to 10 hours]
• Half-Life of Insulin Aspart, t1/2 [Time frame: 0 to 10 hours]
• Area Under The Curve (AUC) of Glucose Infusion Rate(GIR) From Time 0 to 2 Hours Post-Dose , AUCGIR0-2h [Time frame: 0 to 2 hours]
• Area Under The Curve (AUC) of Glucose Infusion Rate(GIR) From 2 Hours Post-dose To End Of Clamp At Time T, AUCGIR2-t [Time frame: 2 to 10 hours]
• Time Until Maximum Glucose Infusion Rate Is Reached, TGIRmax [Time frame: 0 to 10 hours]
• Time To Onset Of Action, Tonset [Time frame: 0 to 10 hours]

Eligibility criteria

Inclusion criteria

• Healthy male participants aged 18 to 55 years (inclusive).
• Body weight: Male ≥ 50.0 kg, body mass index \[BMI = weight (kg)/height2 (m2)\] between 19.0 and 28.0 kg/m2 (inclusive).
• Individuals with normal vital signs or abnormalities without clinical significance (normal reference range: 90 mmHg ≤ systolic blood pressure (supine) < 140 mmHg, 60 mmHg ≤ diastolic blood pressure (supine) < 90 mmHg, 60 beats/min ≤ pulse < 100 beats/min, 36.0°C ≤ body temperature ≤ 37.0°C).
• Normal glucose tolerance (3.90 mmol/L < fasting plasma glucose (FPG) < 6.10 mmol/L, and 2-hour postprandial blood glucose after oral glucose tolerance test (OGTT) < 7.80 mmol/L), glycosylated haemoglobin value between 4.0% and 6.0% (inclusive), and normal insulin secretion function (as determined by the investigator based on insulin release test results).
• Has fully understood the nature, significance, potential benefits, possible inconveniences, and potential risks of the trial before participation, voluntarily participates in this clinical trial, being able to communicate well with the investigator, complying with all study requirements, and has signed the written informed consent form.

Exclusion criteria

• History of specific allergies (e.g., asthma, urticaria, eczema), or those allergic to any drug, food, or pollen, or known to be allergic to insulin;
• History of hereditary galactose intolerance, lactase deficiency, or glucose-galactose malabsorption;
• Has clinically significant abnormal conditions requiring exclusion, including but not limited to system disorders of the nervous, cardiovascular, hematological and lymphatic, immune, renal, hepatic, gastrointestinal, respiratory, metabolic, and skeletal systems, especially a history of hypoglycemia, hypokalemia, orthostatic hypotension, syncope or blackout, diabetes mellitus, or a family history of diabetes mellitus (first-degree relatives);
• Has a history of severe vomiting, diarrhoea within 7 days prior to the trial, or has any other disease or physiological condition that may interfere with the trial results;
• Has undergone surgery within 3 months prior to the study, or plans to undergo surgery during the study period; or has undergone any surgery that may affect drug absorption, distribution, metabolism, or excretion;
• Has a history of asthma or epilepsy;
• Has participated in any other investigational product or device clinical trial and received investigational product within 6 months prior to the study;
• Has taken any medications that alter liver enzyme activity within 28 days prior to the trial (common liver enzyme inducers: barbiturates (phenobarbital is the most common), carbamazepine, aminoglutethimide, griseofulvin, meprobamate, phenytoin, glutethimide, rifampicin, dexamethasone; common liver enzyme inhibitors: chlorpromazine, cimetidine, ciprofloxacin, metronidazole, chloramphenicol, sulfonamides);
• Has taken any medications that affect the hypoglycemic effect of insulin within 28 days prior to the trial (e.g., corticosteroids, danazol, diazoxide, diuretics, epinephrine, albuterol, terbutaline, glucagon, growth hormone, thyroid hormones, beta-blockers, etc.);
• Has used any prescription drugs, over-the-counter drugs, health products, traditional Chinese medicines, or received vaccinations within 14 days prior to the trial;
• Has any clinically significant abnormality identified by the investigator in general physical examination, laboratory tests (including hematology, blood biochemistry, coagulation, urinalysis, etc.), or 12-lead ECG within 14 days prior to the study;
• Has clinically significant abnormalities in glutamic acid decarboxylase autoantibodies (GAD), islet cell cytoplasmic autoantibodies (ICA), or insulin autoantibodies (IAA) results as judged by the investigator;
• Has clinically significant abnormalities in hepatitis B surface antigen, hepatitis C antibody, human immunodeficiency virus (HIV) antibody, or syphilis-specific antibody tests;
• Has a breath alcohol test result > 0.0 mg/100 mL or a positive drug abuse screening;
• Has used any illicit drugs within one year prior to the trial;
• Has consumed more than 14 units of alcohol per week within 3 months prior to the trial (1 unit = 17.7 mL of ethanol, i.e., 1 unit = 354 mL of beer with 5% alcohol, or 44 mL of liquor with 40% alcohol, or 147 mL of wine with 12% alcohol), or is unable to abstain from alcohol during the trial;
• Has smoked more than 5 cigarettes per day on average within 3 months prior to the trial, or is unable to stop using any tobacco products or nicotine-containing products (e.g., nicotine patches, chewing gum, etc.) during the trial;
• Has excessively consumed tea, coffee, and/or caffeine-rich beverages (more than 8 cups per day, 1 cup = 250 mL) within 3 months prior to the trial;
• Has consumed any food or beverages rich in caffeine/xanthine or other special ingredients (such as strong tea, coffee, chocolate, cola, animal offal, grapefruit, grapefruit juice, pitaya, mango, etc.) from screening to 3 days prior to dosing and the diet is judged by the investigator to potentially affect the absorption, distribution, metabolism, and excretion of the drug, or is unable to abstain from such foods or beverages during the trial;
• Has had blood loss or donated more than 200 mL of blood, received a blood transfusion, or used blood products within 3 months prior to the trial, or plans to donate blood during the trial or within 6 months after the last dose;
• Has a pregnancy or sperm donation plan from 2 weeks prior to study start until 6 months after the last dose of study drug, and is unwilling or fails to take effective contraception;
• Is unable to eat normally or has swallowing difficulties, has special dietary requirements, or is unable to comply with the standardized dietary protocol for the trial;
• Is engaged in high-altitude work, motor vehicle driving, or other mechanical operations with potential safety hazards;
• Has poor tolerance to venipuncture, or a history of syncope induced by blood or needle exposure;
• Has been deemed by the investigator to have poor compliance or has any other factors unsuitable for participation in this trial.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Triple blind

Primary purpose

Health services research

Study locations

China · 1 center

• The Second Affiliated Hospital of Xingtai Medical College (Xingtai Cancer Hospital) — Xingtai

Identifiers

NCT: NCT07600944 · TUL-MDYDS(PK/PD)202602

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗