A Study to Compare Pharmacokinetics and Pharmacodynamics of RinGlar® to Lantus® in Type 1 Diabetes Mellitus Patients

Study Overview
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Brief Summary
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Pharmacokinetics and pharmacodynamics study of 2 formulation of insulin glargine (RinGlar® GEROPHARM vers. Lantus® Sanofi-Aventis)

Detailed Description
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A randomized double blinded two-way crossover single-dose pharmacokinetics and pharmacodynamics study of RinGlar® (LLC GEROPHARM, Russia) versus Lantus® (Sanofi-Aventis) in Type 1 Diabetes Mellitus Patients using the euglycemic clamp technique

Official Title
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A Randomized Double Blinded Two-way Crossover Single-dose Pharmacokinetics and Pharmacodynamics Study of RinGlar® (LLC GEROPHARM, Russia) Versus Lantus® (Sanofi-Aventis) in Type 1 Diabetes Mellitus Patients Using the Euglycemic Clamp Technique

Conditions
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Clamp Study

Intervention / Treatment
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* Drug: RinGlar®
* Drug: Lantus®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent. Caucasian males having confirmed diabetes mellitus type 1 (WHO criteria) for at least 12 months prior to screening. Age of 18-65 (both incl.). HbA1С ≤ 8,0 %. Insulin therapy in stable doses at least 3 months. Total dose of insulin ≤ 1,2 IU/kg per day. At least 6 months of Lantus use. C-peptide ≤ 0,3 nM/L (or 0,5 ng/mL). Body mass index equal to 18.5-32.0 kg/m2. Subject must use, with their partner, methods of highly effective contraception throughout the study. Subject is able and willing to comply with the requirements of the study protocol. Exclusion Criteria: Acute inflammatory diseases within 3 weeks before the screening period. History or presence of uncontrolled diabetes mellitus for 6 months prior to screening. Clinically significant diabetes mellitus complications (proliferative retinopathy, severe diabetic neuropathy, diabetic nephropathy (CKD-EPI < 60 mL/min/1,73 m2), diabetic foot). Clinically significant deviations in basic vital signs (blood pressure, heart rate, respiration rate, body temperature), ECG and lab tests. Deep vein thrombosis of lower extremities in a history of life or in a family history. Taking medications (excl. insulin and ACE-inhibitors), phytopreparations, biologically active supplements less than 14 days before screening. Donor blood donation or another blood loss, less than 3 months before the study. Recovery after surgery process. Mental, physical and other reasons that do not allow to adequately assess their behavior and properly fulfill the conditions of the research protocol, including psychiatric disorders. History of significant drugs abuse conditions for 3 years prior to screening. Positive testing for drugs. Receiving more than 10 units. alcohol per week (1 unit of alcohol is equivalent to 0.5 liters of beer, 200 ml of wine or 50 ml of strong alcohol) or anamnestic information about alcoholism. Positive testing for alcohol. Nicotine dependence (use of tobacco less than 6 months before the start of screening). Positive test results for hepatitis C or hepatitis B, HIV, syphilis. Presence of suspicions of an inflammatory disease of the urinary system as a result of urinalysis. Weighed allergic anamnesis. Presence of oncology disease in the anamnesis 5 years prior the start of screening. Organ transplantation in anamnesis (excl. cornea transplantation at least 3 month prior the IP administration). Participation in a clinical trial of any medications less than 3 months before the IP administration. Any other conditions that make it difficult, according to the informed opinion of the investigating physician, that volunteer participation in studies. History of hypersensitivity to insulin, heparin and excipients of the drugs using in study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: two-way crossover
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RinGlar®<br>Single subcutaneous administration of RinGlar® in dose 0.6 Units/kg | Drug: RinGlar®<br>* Single subcutaneous administration of RinGlar® in dose 0.6 Units/kg<br>* Other names: insulin glargine;|
| Active Comparator: Lantus®<br>Single subcutaneous administration of Lantus® in dose 0.6 Units/kg | Drug: Lantus®<br>* Single subcutaneous administration of Lantus® in dose 0.6 Units/kg<br>* Other names: insulin glargine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC GIR(0-t) | Pharmacodynamic of insulin glargine by Assessment of GIR Area Under the Curve From Time Zero Extrapolated to t (AUC(0-t)) | 0 hours (pre-dose), as well as at, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330, 360, 420, 480, 540, 600, 660, 720, 780, 840, 900, 960, 1020, 1080, 1140, 1200, 1260, 1320, 1380, 1440 minutes post-dose | 
| AUC(0-t) | Pharmacokinetics of insulin glargine by Assessment of Area Under the Curve From Time Zero Extrapolated to t (AUC(0-t)) | -60, -30 and 0 hours (pre-dose), as well as at, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330, 360, 420, 480, 540, 600, 660, 720, 780, 840, 900, 960, 1020, 1080, 1140, 1200, 1260, 1320, 1380, 1440 minutes post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics, Pharmacodynamics, Insulin glargine