PK/PD Biosimilarity Study of Gan & Lee Insulin Glargine Injection vs.US & EU Lantus® in Type 1 Diabetes Mellitus Patients

Study Overview
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Brief Summary
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Primary objectives: To demonstrate biosimilarity with regard to the total and maximum pharmacokinetic exposure during one dosing interval (AUC ins. 0-24h, Cins. max) of Gan & Lee Insulin Glargine with Lantus® (US RLD / EU RP) in subjects with type 1 diabetes To demonstrate biosimilarity with regard to the total and maximum pharmacodynamic response during one dosing interval (AUC GIR.0-24h, GIR max) of Gan & Lee Insulin Glargine with Lantus® (US RLD / EU RP) in subjects with type 1 diabetes Secondary objectives: To compare the pharmacokinetic and pharmacodynamic properties of Gan & Lee Insulin Glargine and of Lantus® (US RLD / EU RP) To assess the safety and tolerability of Gan & Lee Insulin Glargine and of Lantus® (US RLD / EU RP)

Official Title
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A Glucose Clamp Trial Investigating the Biosimilarity of Gan & Lee Insulin Glargine Injection (Insulin Glargine 100 U/mL) With US and EU Lantus® Comparator Products in Patients With Type 1 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: Gan & Lee Insulin Glargine Injection


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 performed during normal management of the subject). Male subjects with type 1 diabetes mellitus for at least 12 months prior to screening as diagnosed clinically. Age between 18 and 64 years, both inclusive. Body Mass Index (BMI) between 18.5 and 29.0 kg/m^2, both inclusive. HbA1c <= 9.0%. Fasting negative C-peptide (<= 0.30 nmol/L). Total insulin dose of < 1.2 (I)U/kg/day. Stable insulin regimen for at least 2 months prior to screening (with respect to safety of the subject and scientific integrity of the trial). Considered generally healthy (apart from type 1 diabetes mellitus) 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 IMPs or related products Previous participation in this trial. Participation is defined as randomized Receipt of any medicinal product in clinical development within 30 days or 5 half-lives (whichever is longer) before randomization in this trial History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction Any history or presence of cancer except basal cell skin cancer or squamous cell skin cancer as judged by the Investigator Any history or presence of clinically relevant comorbidity (with the exception of conditions associated with diabetes mellitus), or signs of acute illness, as judged by the Investigator Proliferative retinopathy or maculopathy (based on a recent (<1.5 years) ophthalmologic examination) and/or severe neuropathy, in particular autonomic neuropathy, as judged by the Investigator Recurrent severe hypoglycemia (more than 1 severe hypoglycemic event during the past 6 months) or hypoglycemic unawareness 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 Significant history of alcoholism or drug abuse as judged by the Investigator or consuming more than 24 grams alcohol/day Symptomatic hypotension or supine blood pressure at screening (after resting for at least 5 min in supine position) outside the range of 90-140 mmHg for systolic or greater than 90 mmHg for diastolic pressure Heart rate at rest outside the range of 50-90 beats per minute Clinically significant abnormal standard 12-lead ECG after 5 minutes resting in supine position at screening, as judged by the Investigator A positive result in the alcohol and/or urine drug screen at the screening visit Not able or willing to refrain from smoking and use of nicotine substitute products one day before and during the inpatient period 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 Any medication (prescription and non-prescription drugs) within 14 days before IMP administration, with the exception of occasional use of Paracetamol or NSAIDs Blood donation or blood loss of more than 500 mL within the last 3 months Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation Fertile male with female partner(s) without using a highly effective contraceptive method in combination with spermicide-coated condoms from the first dosing until 1 month after dosing

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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No

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
Interventional Model Description: The trial will be a randomized, double-blind, multicenter, single-dose, 3-way crossover, 3-treatment, euglycemic glucose clamp trial in male subjects with type 1 diabetes mellitus
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lantus ® US<br>Insulin glargine (Lantus®, product approved and marketed in the USA (US RLD)), 100 U/mL in 3 mL pre-filled pens | Drug: Gan & Lee Insulin Glargine Injection<br>* All IMPs will be administered as a 0.5 U/kg single subcutaneous dose by a pre-filled pen.<br>|
| Active Comparator: Lantus ® EU<br>Insulin glargine (Lantus®, product marketed in Germany (EU RP)), 100 U/mL in 3 ml pre-filled pens | Drug: Gan & Lee Insulin Glargine Injection<br>* All IMPs will be administered as a 0.5 U/kg single subcutaneous dose by a pre-filled pen.<br>|
| Experimental: Gan & Lee Insulin Glargine<br>Insulin glargine 100 U/mL in 3 mL pre-filled pens | Drug: Gan & Lee Insulin Glargine Injection<br>* All IMPs will be administered as a 0.5 U/kg single subcutaneous dose by a pre-filled pen.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK endpoint | AUCins. 0 - 24h, area under the serum insulin concentration curve from 0 to 24. hours | Up to 24 hours | 
| PK endpoint | Cins.max, maximum observed insulin concentration. | Up to 30 hrs | 
| PD endpoint | AUC GIR.0-24h, area under the glucose infusion rate curve from 0 to 24 hours. | Up to 24 hours | 
| PD endpoint | GIR max, maximum observed glucose infusion rate | Up to 30 hrs | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary PK endpoint | AUC ins.0-12h, AUC ins.12 - 24h, AUC ins.0 -inf., areas under the serum insulin concentration curve in the indicated time intervals | Up to 24 hrs | 
| Secondary PK endpoint | tmax.ins, time to maximum observed serum insulin concentration | Up to 30 hrs | 
| Exploratory PK endpoint | t½, terminal serum elimination half-life calculated as t½=ln2/λz and | Up to 30 hrs | 
| Exploratory PK endpoint | λz, terminal elimination rate constant | Up to 30 hrs | 
| Secondary PD endpoint | AUC GIR.0 - 12h, AUC GIR.12 - 24h, areas under the glucose infusion rate curve in the indicated time-intervals | Up to 24 hrs | 
| Secondary PD endpoint | AUC GIR.0 - last, area under the glucose infusion rate curve from 0 hours until the end of clamp | Up to 30 hrs | 
| Secondary PD endpoint | t max.GIR, time to maximum glucose infusion rate | Up to 30 hrs | 
| Exploratory PD endpoint | Duration of action, time until blood glucose levels is consistently above 150 mg/dL | Up to 30 hrs | 
| Exploratory PD endpoint | Time to onset of action, time from trial product administration until blood glucose concentration has decreased at least 5 mg/dL from baseline, where baseline is defined as the mean of blood glucose levels from - 6 to - 2 minutes before trial product administration as measured by ClampArt. | Up to 30 hrs | 
| Safety endpoints | As measured by treatment-emergent adverse events | Up to 12 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Diabetes Type 1, Type 1, Basal, Insulin, Glargine, T1DM, Diabetes Mellitus, Insulin Dependent Diabetes