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

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

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

Study Overview

• Status: Completed
• Conditions: Clamp Study
• Intervention / Treatment: Drug: RinGlar®; Drug: Lantus®

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 117036
    • Endocrinology Research Centre
  • Saint Petersburg, Russian Federation, 197341
    • Almazov National Medical Research Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Signed informed consent.
2. Caucasian males having confirmed diabetes mellitus type 1 (WHO criteria) for at least 12 months prior to screening.
3. Age of 18-65 (both incl.).
4. HbA1С ≤ 8,0 %.
5. Insulin therapy in stable doses at least 3 months. Total dose of insulin ≤ 1,2 IU/kg per day.
6. At least 6 months of Lantus use.
7. C-peptide ≤ 0,3 nM/L (or 0,5 ng/mL).
8. Body mass index equal to 18.5-32.0 kg/m2.
9. Subject must use, with their partner, methods of highly effective contraception throughout the study.
10. Subject is able and willing to comply with the requirements of the study protocol.

Exclusion Criteria:

1. Acute inflammatory diseases within 3 weeks before the screening period.
2. History or presence of uncontrolled diabetes mellitus for 6 months prior to screening.
3. Clinically significant diabetes mellitus complications (proliferative retinopathy, severe diabetic neuropathy, diabetic nephropathy (CKD-EPI < 60 mL/min/1,73 m2), diabetic foot).
4. Clinically significant deviations in basic vital signs (blood pressure, heart rate, respiration rate, body temperature), ECG and lab tests.
5. Deep vein thrombosis of lower extremities in a history of life or in a family history.
6. Taking medications (excl. insulin and ACE-inhibitors), phytopreparations, biologically active supplements less than 14 days before screening.
7. Donor blood donation or another blood loss, less than 3 months before the study.
8. Recovery after surgery process.
9. 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.
10. History of significant drugs abuse conditions for 3 years prior to screening.
11. Positive testing for drugs.
12. 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.
13. Positive testing for alcohol.
14. Nicotine dependence (use of tobacco less than 6 months before the start of screening).
15. Positive test results for hepatitis C or hepatitis B, HIV, syphilis.
16. Presence of suspicions of an inflammatory disease of the urinary system as a result of urinalysis.
17. Weighed allergic anamnesis.
18. Presence of oncology disease in the anamnesis 5 years prior the start of screening.
19. Organ transplantation in anamnesis (excl. cornea transplantation at least 3 month prior the IP administration).
20. Participation in a clinical trial of any medications less than 3 months before the IP administration.
21. Any other conditions that make it difficult, according to the informed opinion of the investigating physician, that volunteer participation in studies.
22. History of hypersensitivity to insulin, heparin and excipients of the drugs using in study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RinGlar®; Single subcutaneous administration of RinGlar® in dose 0.6 Units/kg	Drug: RinGlar®; Single subcutaneous administration of RinGlar® in dose 0.6 Units/kg; Other Names: insulin glargine
Active Comparator: Lantus®; Single subcutaneous administration of Lantus® in dose 0.6 Units/kg	Drug: Lantus®; Single subcutaneous administration of Lantus® in dose 0.6 Units/kg; Other Names: insulin glargine

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Geropharm

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2017
• Primary Completion (Actual): February 16, 2018
• Study Completion (Actual): February 16, 2018

Study Registration Dates

• First Submitted: September 23, 2019
• First Submitted That Met QC Criteria: September 23, 2019
• First Posted (Actual): September 24, 2019

Study Record Updates

• Last Update Posted (Actual): September 24, 2019
• Last Update Submitted That Met QC Criteria: September 23, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Pharmacodynamics; Insulin glargine
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Glargine
• Other Study ID Numbers: GLARGIN-CL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No