Efficacy and Safety of Insulin Lispro Biphasic 25 Compared to Humalog® Mix 25 in Type 2 Diabetes Mellitus Patients

An Open-label, Randomized, Multi-center, Parallel-group Clinical Trial Comparing the Efficacy and Safety of Insulin Lispro Biphasic 25 ("Geropharm", Russia) Humalog® Mix 25 ("Lilly France", France) in Type 2 Diabetes Mellitus Patients

The study is designed to approve non-inferior efficacy and safety of Insulin Lispro Biphasic 25 ("Geropharm") compared to Humalog® Mix 25 in Type 2 Diabetes Mellitus Patients.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Diabetes Mellitus
• Intervention / Treatment: Drug: Humalog Mix25; Drug: Insulin Lispro Biphasic 25

• Study Type: Interventional
• Enrollment (Actual): 210
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Chelyabinsk, Russian Federation, 454000
    • Chelyabinsk Railway Clinical Hospital
  • Moscow, Russian Federation, 117036
    • Endocrinology Research Centre (Moscow)
  • Moscow, Russian Federation, 119034
    • Moscow Endocrinological Dispensary
  • Moscow, Russian Federation, 109386
    • Railway Clinical Hospital N.A. Semashko
  • Nizhny Novgorod, Russian Federation, 603126
    • Nizhny Novgorod Regional Clinical Hospital
  • Petrozavodsk, Russian Federation, 185000
    • V.A. Baranov Republic Hospital
  • Rostov-on-Don, Russian Federation, 344022
    • Rostov State Medical University
  • Saint Petersburg, Russian Federation, 194354
    • City Hospital № 2
  • Saint Petersburg, Russian Federation, 194358
    • City Polyclinic № 117
  • Saint Petersburg, Russian Federation, 196084
    • Institute of Medical Research
  • Saint Petersburg, Russian Federation, 196143
    • Research Center Eco-Safety
  • Saint Petersburg, Russian Federation, 199106
    • Pokrovskaya Municipal Hospital
  • Saint Petersburg, Russian Federation, 195176
    • City Polyclinic № 17
  • Saint Petersburg, Russian Federation, 192177
    • City Polyclinic № 77
  • Saint Petersburg, Russian Federation, 197706
    • City Hospital №40
  • Samara, Russian Federation, 443067
    • Diabetes Center
  • Saratov, Russian Federation, 410030
    • Clinical City Hospital № 9
  • Tomsk, Russian Federation, 634050
    • Siberian State Medical University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Signed written consent
• Clinical diagnosis of type 2 diabetes mellitus for at least 6 months prior to screening
• Glycosylated hemoglobin (HbA1c) level of 7.6 to 12.0 % at screening (both values inclusive)
• Body mass index (BMI) of 18.0 to 35 kg/m2 at screening (both values inclusive)
• Stable doses OADs for at least 3 months prior to treatment of experimental drug
• Female patients of childbearing potential who are willing to use two acceptable methods of contraception, (e.g., intra-uterine device plus condom, spermicidal gel plus condom, diaphragm plus condom, etc.), from the time of screening and for the duration of the trial, through trial completion

Exclusion Criteria:

• Acute inflammation disease for 3 weeks prior to screening
• Deviation of the laboratory results conducted during the screening:

Hemoglobin value < 9,0 g/dl; Hematocrit value < 30 %; ALT and AST value > 2 folds as high as maximal normal value; Serum bilirubin value > 1.5 folds as high as maximal normal value

• History of hematological disorders that can affect the reliability of HbA1c estimation (hemoglobinopathies, hemolytic anemia, etc.)
• Serious blood loss for 3 months prior to screening (blood donation, surgery procedure, etc.)
• Contraindication to the use of insulin Lispro Biphasic 25
• Insulin resistance over 1.5 U/kg insulin pro day
• Presence of insulin antibodies in the blood at the screening ˃10 U/ml
• Use of 3 or more oral antidiabetic drugs (OAD)
• Presence of severe diabetes complications
• History or presence of uncontrolled diabetes mellitus for 6 months prior to screening
• Deviation of vital signs, which can influence to results
• History of administration of glucocorticoids for 1 year prior to screening
• History of autoimmune disease, except controlled autoimmune thyroid disease
• Pregnant and breast-feeding women
• History of hypersensitivity to any of the active or inactive ingredients of the insulin/insulin analogue preparations used in the trial, OR history of significant allergic drug reactions
• Administration of any immunosuppressive drugs (Cyclosporinum, Methotrexatum)
• Incomplete recovery after surgery procedure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Humalog® Mix 25; Insulin Humalog® Mix 25 twice daily, individually glucose-level based administered doses +/- 1 or 2 OADs in stable doses, started before enrollement	Drug: Humalog Mix25; Subcutaneus injections Humalog® Mix 25 twice daily during 4 weeks of glucose-level based dose titration, 24 weeks of treatment with stable doses
Experimental: Insulin Lispro Biphasic 25; Insulin Lispro Biphasic 25 twice daily, individually glucose-level based administered doses +/- 1 or 2 OADs in stable doses, started before enrollement	Drug: Insulin Lispro Biphasic 25; Subcutaneus injections Insulin Lispro Biphasic 25 ("Geropharm") twice daily during 4 weeks of glucose-level based dose titration, 24 weeks of treatment with stable doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antibody Response	Change from baseline in titer of antibodies to human insulin	26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting Plasma Glucose Level	Change in fasting plasma glucose level from baseline	26 weeks
Body Mass Index	Change in BMI from baseline	26 weeks
Seven-Point Glucose Testing	Change in seven-point glucose testing results from baseline	26 weeks
Treatment Satisfaction	Change in overall treatment satisfaction (DTSQ score) from baseline	26 weeks
Adverse Events frequency and degree	Hypoglycemic episodes (glucose level < 3.9 mmol/l) frequency Occurrence of local reactions at injection sites Occurrence allergic reactions	26 weeks (4+22 weeks)
HbA1c	Change in HbA1c from baseline	26 weeks
Insulin Dose	Change in total insulin dose per body weight (U/kg) from baseline	26 weeks

Collaborators and Investigators

• Sponsor: Geropharm
• Investigators: Principal Investigator: Aleksandr Yu Mayorov, MD, Endocrinology Research Centre

Publications and helpful links

General Publications

• Mayorov AY, Mosikian AA, Alpenidze DN, Makarenko IE, Orlova VL, Lunev IS, Verbovaya MV, Zinnatulina BR, Khokhlov AL, Drai RV. Efficacy and safety of GP40021 insulin lispro biphasic compared with Humalog Mix 25 in Type 2 diabetes mellitus patients. J Comp Eff Res. 2021 Jan;10(1):55-66. doi: 10.2217/cer-2020-0064. Epub 2020 Dec 23.

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2018
• Primary Completion (Actual): January 15, 2019
• Study Completion (Actual): April 18, 2019

Study Registration Dates

• First Submitted: July 5, 2019
• First Submitted That Met QC Criteria: July 16, 2019
• First Posted (Actual): July 17, 2019

Study Record Updates

• Last Update Posted (Actual): July 17, 2019
• Last Update Submitted That Met QC Criteria: July 16, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Insulin; Diabetes Mellitus, Type 2; Lispro Biphasic
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin Lispro
• Other Study ID Numbers: LISPRO25-IM

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