Human Bioequivalence Test of Liraglutide Injection

Study Overview
=================
Brief Summary
-----------------
To evaluate the bioequivalence of The liraglutide injection produced by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. and Victoza® produced by Novo Nordisk (China) Pharmaceutical Co., Ltd for single dose in healthy subjects,so as to provide reference for clinical evaluation and clinical medication;To observe the safety of the test preparation liraglutide injection and the reference preparation Victoza ® in healthy subjects.

Official Title
-----------------
Human Bioequivalence Test of Liraglutide Injection

Conditions
-----------------
Type 2 Diabetes

Intervention / Treatment
-----------------
* Drug: Liraglutide injection
* Drug: Victoza


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Sign the informed consent form before the trial, fully understand the trial purpose, process and possible adverse reactions; Able to complete the study according to the requirements of protocol; Aged between 18 and 60 years old, both men and women; Male ≥50kg, female ≥45kg,body mass index(BMI)=weight (kg)/height 2 (m2), BMI is 18-28 kg/m2 (including the critical value); No mental abnormalities, no history of cardiovascular system, nervous system, respiratory system, digestive system, urinary system, endocrine system or metabolic abnormalities; Normal or abnormal vital signs, physical examination, laboratory examination, electrocardiogram, and imageological examination have no clinical significance; The female blood pregnancy test is not pregnant, and the subjects (including male subjects) have no pregnancy plan and voluntarily take effective contraceptive measures from 2 weeks before administration to at least 3 months after the last use of the study drug. See the appendix for specific contraceptive measures. Exclusion Criteria: Previous disease of the neuropsychiatric system, respiratory system, cardiovascular system, digestive system, hemo-lymphatic system, liver and kidney dysfunction, endocrine system, musculoskeletal system, or other disease that the investigator determines may affect drug metabolism or safety; Have a history of fainting needles, fainting blood; Known allergy to Liraglutide and its metabolites or any of the excipients of the formulation; Those who smoked more than 5 cigarettes per day during the 3 months before the trial. History of drug and/or alcohol abuse (drinking 14 units of alcohol per week: 1 unit = 360 ml of beer or 45 ml of 40% alcoholic spirits or 150 ml of wine); Donated blood or lost a lot of blood (> 450 ml) within 2 months before taking the study drug ; Have taken any drug that changes liver enzyme activity 28 days before taking the study drug (such as liver drug enzyme inhibitor chlorpromazine, cimetidine, ciprofloxacin, metronidazole, etc.; liver drug enzyme inducer barbital Drugs, carbamazepine, rifampicin, dexamethasone, etc.); Have taken any prescription, over-the-counter, vitamin product or herbal medicine within 1 month prior to the use of the study drug; During the trial it is necessary to use tobacco, alcohol, and caffeine-containing drinks, or certain foods that may affect metabolism (such as grapefruit, grapefruit juice, etc.), or major changes in diet or exercise habits before the test, or other effects that affect drug absorption, Factors such as distribution, metabolism, excretion, etc; Have taken the study drug or participated in the drug clinical trial within 2 months before taking the study drug; Positive for hepatitis (including hepatitis B and C), HIV or syphilis at screening; Female subjects are breastfeeding or have a positive serum pregnancy result during the screening period or during the test; Those who have been screened positive for drugs or have a history of drug abuse in the past five years or have used drugs in the 3 months before the trial; Blood collection is difficult or cannot tolerate venipuncture blood collection; Acute illness during the screening phase or before study medication; The subject is unable or can not comply with ward management regulations; The subject is unable to complete the study due to personal reasons; Other cases judged by researchers to be unsuitable for selection.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liraglutide injection + Victoza<br>Subjects receive liraglutide injection in the first cycle and Victoza in the second cycle. | Drug: Liraglutide injection<br>* Human glucagon-like peptides-1 analogue<br>Drug: Victoza<br>* Human glucagon-like peptides-1 analogue<br>|
| Experimental: Victoza +Liraglutide injection<br>Subjects receive Victoza in the first cycle and liraglutide injection in the second cycle. | Drug: Liraglutide injection<br>* Human glucagon-like peptides-1 analogue<br>Drug: Victoza<br>* Human glucagon-like peptides-1 analogue<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum (peak) plasma drug concentration(Cmax) | Maximum (peak) plasma drug concentration | 0 hour（pre-dose,within 60mins） to 72hours after administration on day1 and day 15. | 
| Time to reach maximum (peak) plasma concentration following drug administration (Tmax) | Time to maximum concentration | 0 hour（pre-dose,within 60mins） to 72hours after administration on day1 and day 15. | 
| Area under the plasma concentration-time curve from time zero to time t (AUC0-t) | The area under the plasma concentration curve from 0 to infinity | 0 hour（pre-dose, within 60 mins） to 72 hours after administration on day1 and day 15. | 
| Terminal disposition rate constant/terminal rate constant (λz) | Apparent end elimination rate constant | 0 hour（pre-dose, within 60 mins） to 72 hours after administration on day1 and day 15. | 
| Elimination half-life (t1/2) | The time required for the highest concentration of the drug in plasma to decrease by half | 0 hour（pre-dose, within 60 mins） to 72 hours after administration on day1 and day 15. | 
| Apparent total clearance of the drug from plasma after oral administration (CL/F) | Apparent total body clearance | 0 hour（pre-dose, within 60 mins） to 72 hours after administration on day1 and day 15. | 
| Apparent volume of distribution after non-intravenous administration (Vd/F) | Apparent volume of distribution | 0 hour（pre-dose, within 60 mins） to 72 hours after administration on day1 and day 15. | 
| Bioavailability (systemic availability of the administered dose) | Relative bioavailability | 0 hour（pre-dose, within 60mins） to 72 hours after administration on day1 and day 15. | 
| Adverse Event, Serious Adverse Event and Drug Combination | Monitor the safety indicators of subjects during the trial | up to day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| body temperature | abnormal body temperature | 1 hour before administration and 2 hours, 10 hours, 24 hours, 48 hours, 72 hours after administration on day 1 and day 15 | 
| pulse | abnormal pulse | 1 hour before administration and 2 hours, 10 hours, 24 hours, 48 hours, 72 hours after administration on day 1 and day 15 | 
| blood pressure | abnormal blood pressure | 1 hour before administration and 2 hours, 10 hours, 24 hours, 48 hours, 72 hours after administration on day 1 and day 15 | 
| clinical symptoms | Any discomfort spontaneously reported by the subject | From the screening period to day 18 after the first administration | 
| The Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 (physical examination) | Monitor the safety indicators of subjects during the trial，For example: skin, mucous membrane, head (head, eyes, ears, nose, mouth), neck, chest (chest, breast, lung, heart), abdomen (liver, gallbladder, spleen, kidney, bladder), spine, limbs, nervous system, lymph nodes, etc，and calculate the Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | From the screening period to day 18 after the first administration | 
| The Number of participants with abnormal laboratory examinations | laboratory examination, such as liver function, kidney function, coagulation function, blood routine, urine routine | From the screening period to day 18 after the first administration |