A Study Evaluating the Bioavailability of Oral Insulin (N11005)

Study Overview
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Brief Summary
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The objective of this study was to preliminarily verify whether the oral insulin N11005 is a prandial insulin by assessing the PK, PD, and safety profiles of N11005.

Official Title
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Research on Clinical Application of New Therapies for Diabetes and Its Complications and Related Translational Medicine Research

Conditions
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PK, PD, and Safety

Intervention / Treatment
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* Drug: N11005
* Drug: Novolin R


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1) Volunteer to participate in the trial and sign an informed consent form; 2) 18-45 years old (including 18 and 45 years old) healthy male subjects (without heart, liver, kidney, digestive tract, neurological diseases, and metabolic abnormalities in the 4 weeks before screening; No abnormal clinically significant vital signs results, physical examination results, laboratory examination results and electrocardiogram examination results judged by the investigator at the time of screening); 3) BMI (body mass index): between 19-24 Kg/m2, including 19 and 24 Kg/m2; 4) Normal glucose tolerance (fasting plasma glucose [FPG] <6.1 mmol/L, and oral glucose tolerance test [OGTT] 2-hour postprandial blood glucose <7.8 mmol/L); 5) No family history of diabetes, obesity, etc.; 6) Insulin secretion function is normal (confirmed by insulin release test (IRT) judged by the investigator); 7) There is no planned parenthood during the study period, and it is agreed to use reliable contraceptive measures during the study period until 4 weeks after the last administration of the study drug; 8) Be able to communicate well with researchers and complete research in accordance with research regulations. Exclusion Criteria: 1). Those who have serious systemic diseases, infectious diseases or mental disorders; 2). The results of human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibody, syphilis test are positive; 3). Those who have used any prescription drugs, Chinese herbal medicines and/or over-the-counter drugs (except for subjects with occasional and restricted use of paracetamol) and health products (except routine vitamin supplements) within 2 weeks before screening; 4). Those who donated more than 400 mL of blood within 3 months before screening; 5). Severe smokers (25 or more cigarettes per day); 6). Alcoholics (drinking 14 units of alcohol per week: 1 unit = 285 mL of beer, or 25 mL of spirits, or 100 mL of wine), or those who have a positive alcohol breath test result; 7). Those who have a history of drug abuse or have a positive urine test for illegal drugs; 8). Those who are known or suspected to be allergic to insulin and/or its excipients; 9). Those who have participated in other clinical trials within 3 months before screening, or plan to participate in other clinical trials during the trial period or within 1 month after the end of the trial; 10). Those who have any food allergies or have special dietary requirements and cannot follow a unified diet; 11). Those who have undergone gastrointestinal surgery before screening, or have a history of gastric obstruction or impaired gastrointestinal motility; 12). Those who are using gastric mucosal protective agents during screening; 13). Those who are deemed unsuitable to participate in this trial after the researcher's evaluation;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: T group<br> | Drug: N11005<br>* oral insulin N11005, 300IU, p.o.<br>|
| Active Comparator: R group<br> | Drug: Novolin R<br>* reference preparation Novolin R, 0.1 IU/Kg, i.h.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | the peak concentration | Pre-dose, 5,10,20,30,40,50,60,75,90,105,120,150,180,210,240,270,300, 330,360,420,480 minutes； | 
| AUC 0-8 h | the AUC for insulin from time zero to 8 hours | Pre-dose, 5,10,20,30,45,10,20,30,40,50,60,75,90,105,120,150,180,210,240,270,300, 330,360,420,480 minutes； | 
| AUCGIR,0-8 h |  | Pre-dose, 0-8 hours | 
| GIRmax |  | Pre-dose, 0-8 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax | time to Cmax | Pre-dose, 5,10,20,30,40,50,60,75,90,105,120,150,180,210,240,270,300,330,360,420,480 minutes； | 
| AUC 0-2 h | the AUC for insulin from time zero to 2 hours | Pre-dose, 5,10,20,30,40,50,60,75,90,105,120 minutes | 
| the elimination half-life (t1/2) of serum insulin |  | Pre-dose, 5,10,20,30,40,50,60,75,90,105,120,150,180,210,240,270,300, 330,360,420,480 minutes； | 
| the AUC for insulin from time zero to 4 h |  | Pre-dose, 5,10,20,30,40,50,60,75,90,105,120,150,180,210,240 minutes | 
| the AUC for insulin from time zero to infinite time |  | Pre-dose, 5,10,20,30,45,10,20,30,40,50,60,75,90,105,120,150,180,210,240,270,300, 330,360,420,480 minutes； | 
| AUCGIR，0-2 h |  | Pre-dose, 0-2 hours | 
| AUCGIR，0-4 h |  | Pre-dose, 0-4 hours | 
| tGIRmax |  | Pre-dose, 0-8 hours |