A Study to Compare Pharmacokinetics and Pharmacodynamics of Insulin Lispro to Humalog® in Healthy Subjects

A Randomized Duble Blinded Two-way Crossover Single-dose Pharmacokinetics and Pharmacodynamics Study of Insulin Lispro (LLC "GEROPHARM", Russia) Versus Humalog® (Eli Lilly) in Healthy Subjects Using the Euglycemic Clamp Technique

Pharmacokinetics and pharmacodynamics study Study of 2 formulation of insulin lispro (Insulin Lispro GEROPHARM vers. Humalog® Eli Lilly)

Study Overview

• Status: Completed
• Conditions: Clamp Study
• Intervention / Treatment: Drug: Insulin Lispro; Drug: Humalog®

Detailed Description

A randomized duble blinded two-way crossover single-dose pharmacokinetics and pharmacodynamics study of Insulin Lispro (LLC "GEROPHARM", Russia) versus Humalog® (Eli Lilly) in normal healthy subjects using the euglycemic clamp technique

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Russian Federation
  • Saint Petersburg, Russian Federation, 197342
    • LLL "BioEq"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Signed informed consent.
2. Caucasian males having a confirmed healthy diagnosis as per data of standard clinical, laboratory, and instrumental examination methods.
3. Age of 18-50 (both incl.).
4. Body mass index equal to 18.5-27.0 kg/m2.
5. Volunteers' consent to all restrictions imposed during the study, including adequate methods of contraception.

Exclusion Criteria:

1. Acute inflammatory diseases within 3 weeks before the screening period
2. Episodes of hypoglycemia in the anamnesis, or the presence in the family history of cases of a verified diagnosis of diabetes mellitus in the immediate family
3. Fasting plasma glucose> 6.1 mmol / L
4. HbA1C> 6%
5. Oral glucose tolerance test - blood glucose level ≥ 7.8 mmol / l (2 hours after loading with glucose)
6. Deep vein thrombosis of lower extremities in a history of life or in a family history.
7. Nicotine dependence (use of tobacco less than 6 months before the start of screening)
8. Taking medications, phytopreparations, biologically active supplements less than 14 days before screening
9. 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.
10. Donor blood donation in excess of 450 ml, less than 2 months before the study.
11. Participation in a clinical trial of any medications less than 3 months before the start of screening
12. Positive test results for hepatitis C or hepatitis B, HIV, syphilis.
13. Anamnesis information about drug and / or drug dependence and / or substance abuse.
14. Positive test for alcohol content in the exhaled air.
15. A positive test for the content of drugs in the urine.
16. Presence of suspicions of an inflammatory disease of the urinary system as a result of urinalysis.
17. Presence of mental illnesses in the anamnesis.
18. Mental, physical and other reasons that do not allow to adequately assess their behavior and properly fulfill the conditions of the research protocol.
19. Any other conditions that make it difficult, according to the informed opinion of the investigating physician, that volunteer participation in studies
20. Increased sensitivity in the history of heparin, insulin or any of the excipients of the study drugs
21. Weighed allergic anamnesis
22. Abnormalities of the ECG and laboratory parameters from the norms
23. Deviations in basic vital signs: systolic blood pressure is below 100 mm Hg. or above 130 mm Hg, the diastolic blood pressure is below 70 mm Hg. or above 90 mm Hg; heart rate less than 60 or greater than 80
24. Deviations in basic vital signs: systolic blood pressure <100 mmHg. or> 130 mm Hg, diastolic blood pressure <70 mm Hg. Art. or> 90 mm Hg. Art. heart rate <60 or> 80 per minute.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Insulin Lispro; Single subcutaneous administration of Insulin Lispro in dose 0.3 IU / kg	Drug: Insulin Lispro
Active Comparator: Humalog®; Single subcutaneous administration of Humalog® in dose 0.3 IU / kg	Drug: Humalog®; Other Names: insulin lispro

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Pharmacokinetics of insulin lispro by Assessment of Observed Maximum Plasma Concentration (Cmax)	-60, -30 and 0 hours (pre-dose), as well as at, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 210, 240, 270, 300, 360, 420 and 480 minutes post-dose
AUC(0-t)	Pharmacokinetics of insulin Lispro 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, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 210, 240, 270, 300, 360, 420 and 480 minutes post-dose
GIRmax	Pharmacodynamic of insulin lispro by Maximum Glucose Infusion Rate (GIRmax)	0 hours (pre-dose), as well as at, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 210, 240, 270, 300, 360, 420 and 480 minutes post-dose
AUCGIR0-t	Pharmacodynamic of insulin Lispro 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, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 210, 240, 270, 300, 360, 420 and 480 minutes post-dose

Collaborators and Investigators

• Sponsor: Geropharm

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2016
• Primary Completion (Actual): December 26, 2016
• Study Completion (Actual): December 26, 2016

Study Registration Dates

• First Submitted: July 17, 2018
• First Submitted That Met QC Criteria: July 20, 2018
• First Posted (Actual): July 27, 2018

Study Record Updates

• Last Update Posted (Actual): July 27, 2018
• Last Update Submitted That Met QC Criteria: July 20, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Pharmacodynamics; Insulin Lispro
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Lispro
• Other Study ID Numbers: LISPRO-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