PK/PD Study of Gan & Lee Insulin Aspart Injection vs. US & EU NovoLog®/NovoRapid® in Healthy Males

Study Overview
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Brief Summary
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Primary objective: To demonstrate pharmacokinetic (PK) and pharmacodynamic (PD) equivalence of Gan & Lee Insulin Aspart Injection with both EU-approved NovoRapid® and US-licensed NovoLog® (Reference Products) in healthy male subjects Secondary objectives: To compare the PK and PD parameters of the three insulin aspart preparations To evaluate the single dose safety and local tolerability of the three insulin aspart preparations

Official Title
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A Glucose Clamp Trial Investigating The Biosimilarity of Gan & Lee Insulin Aspart Injection (Insulin Aspart 100 U/ml) With US and EU Insulin Aspart Comparator Products (NovoLog®/NovoRapid®) in Healthy Male Subjects

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: Gan & Lee Insulin Aspart


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated informed consent obtained before any trial-related activities. Trial-related activities are any procedures that would not have been done during normal management of the subject Healthy male subjects Age between 18 and 64 years, both inclusive Body Mass Index (BMI) between 18.5 and 29.0 kg/m^2, both inclusive Fasting plasma glucose concentration <= 5.50 mmol/L (100 mg/dL) at screening Considered generally healthy upon completion of medical history, physical examination, vital signs, ECG and analysis of laboratory safety variables, as judged by the Investigator Exclusion Criteria: Known or suspected hypersensitivity to investigational medicinal products (IMPs) or related product Previous participation in this trial. Participation is defined as randomized Use of other investigational drugs within five half-lives for enrolment or receipt of any medicinal product in clinical development within 30 days before randomization in this trial, whichever is longer History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction. Clinically significant abnormal values for haematology, biochemistry, coagulation, or urinalysis as judged by the Investigator Increased risk of thrombosis, e.g subjects with a history of deep leg vein thrombosis or family history of deep leg vein thrombosis, as judged by the Investigator A positive result in the alcohol and/or urine drug screen at the screening visit Positive to the screening test for Hepatitis Bs antigen or Hepatitis C antibodies and/or a positive result to the test for HIV-1/2 antibodies or HIV-1 antigen Blood donation or blood loss of m ore than 500 mL within the last 3 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gan & Lee Insulin Aspart<br>100 units/mL, 3 ml prefilled pen | Drug: Gan & Lee Insulin Aspart<br>* All three IMPs will be administered as a 0.2 U/kg single dose subcutaneously in the periumbilical area.<br>* Other names: NovoLog® US;|
| Active Comparator: NovoRapid® Insulin Aspart<br>Product approved and marketed in the EU FlexPen100 units/mL prefilled pen | Drug: Gan & Lee Insulin Aspart<br>* All three IMPs will be administered as a 0.2 U/kg single dose subcutaneously in the periumbilical area.<br>* Other names: NovoLog® US;|
| Active Comparator: NovoLog® Insulin Aspart<br>Product approved and marketed in the US FlexPen100 units/mL prefilled pen | Drug: Gan & Lee Insulin Aspart<br>* All three IMPs will be administered as a 0.2 U/kg single dose subcutaneously in the periumbilical area.<br>* Other names: NovoLog® US;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCins.0-12h | PK endpoint: The area under the insulin concentration curve from 0 to 12 hours | 0 -12 hours | 
| Cins.max | PK endpoint: The maximum observed insulin concentration | 0 -12 hours | 
| AUCGIR.0-12h | PD endpoint: The area under the glucose infusion rate curve from 0 to 12 hours | 0 - 12 hours | 
| GIRmax | PD endpoint: The maximum glucose infusion rate | 0 - 12 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCins.0-2h | PK endpoint: The area under the insulin concentration curve from 0 to 2 hours | 0 - 2 hours | 
| AUCins.0-∞ | PK endpoint: The area under the insulin concentration-time curve from 0 hours to infinity | 0 - 12 hours | 
| tins.max | PK endpoint: The time to maximum observed insulin concentration | Up to Day 68 | 
| t50%-ins(early) | PK endpoint: The time to half-maximum insulin concentration before Cins.max | Up to Day 68 | 
| t50%-ins(late) | PK endpoint: The time to half-maximum insulin concentration after Cins.max | Up to Day 68 | 
| t½ | PK endpoint: The terminal serum elimination half-life calculated as t½=ln2/λz | Up to Day 68 | 
| λz | PK endpoint: The terminal elimination rate constant of insulin | Up to Day 68 | 
| AUCGIR.0-2h | PD endpoint: The area under the glucose infusion rate curve from 0 to 2 hours | 0 - 2 hours | 
| tGIR.max | PD endpoint: The time to maximum glucose infusion rate | Up to Day 68 | 
| tGIR.50%-early | PD endpoint: The time to half-maximum glucose infusion rate before GIRmax | Up to Day 68 | 
| tGIR.50%-late | PD endpoint: The time to half-maximum glucose infusion rate after GIRmax | Up to Day 68 | 
| PD endpoint | time to onset of action | Up to Day 68 | 
| Safety and local tolerability | Number of participants experiencing treatment-emergent adverse events | Up to Day 68 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Insulin, Diabetes Mellitus, Basal, Bolus