Efficacy and Safety of Insulin Rinsulin® NPH Compared to Humulin® NPH in Type 2 Diabetes Mellitus Patients

An Open-label, Randomized, Multi-center, Parallel-group Clinical Trial Comparing the Efficacy and Safety of Rinsulin® NPH ("Geropharm", Russia) With Humulin® NPH ("Lilly France", France) in Type 2 Diabetes Mellitus Patients

The study is designed to approve non-inferior efficacy and safety of Rinsulin® NPH compared to Humulin® NPH.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Biological: Insulin Humulin® NPH; Biological: Insulin Rinsulin® NPH

• Study Type: Interventional
• Enrollment (Actual): 201
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Chelyabinsk, Russian Federation, 454000
    • Chelyabinsk Railway Clinical Hospital
  • Moscow, Russian Federation, 119034
    • Moscow Endocrinological Dispensary
  • Moscow, Russian Federation, 121374
    • Moscow Clinical Hospital № 71
  • Nizhny Novgorod, Russian Federation, 603126
    • Nizhny Novgorod Regional Clinical Hospital
  • Petrozavodsk, Russian Federation, 185000
    • V.A. Baranov Republic Hospital
  • Saint Petersburg, Russian Federation, 194354
    • City Hospital № 2
  • Saint Petersburg, Russian Federation, 196084
    • Institute of Medical Research
  • Saint Petersburg, Russian Federation, 196143
    • Research Center Eco-Safety
  • Saint Petersburg, Russian Federation, 192148
    • City Polyclinic № 6
  • Saint Petersburg, Russian Federation, 195176
    • City Polyclinic № 17
  • Saint Petersburg, Russian Federation, 196066
    • Medical Sanitary Unit № 157
  • Saint Petersburg, Russian Federation, 198260
    • Saint Petersburg State Diagnostic Center № 85
  • Samara, Russian Federation, 443067
    • Diabetes Center
  • Yaroslavl, Russian Federation, 150007
    • Clinical Hospital № 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed written consent
• Diabetes mellitus type 2
• Indications for Rinsulin NPH / Humalog NPH treatment
• Glycosylated hemoglobin (HbA1c) level of 6.5 to 12.0 % at screening (both values inclusive)
• Body mass index (BMI) of 18.0 to 35 kg/m2 at screening (both values inclusive).
• 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:

• Age less than 18 years old at screening
• Pregnant and breast-feeding women
• Need of administration of glucocorticoid therapy or any other therapy that may influence glucose level
• Administration of any immunosupressive drugs (Cyclosporinum, Methotrexatum)
• Serological evidence of human immunodeficiency virus (HIV), hepatitis B (HbSAg), hepatitis C (HCVAb) or antibodies to Treponema pallidum (syphilis) at screening.
• 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.
• History of hematological disorders that can affect the reliability of HbA1c estimation (hemoglobinopathies, hemolytic anemia, etc.).
• History or presence of a medical condition or disease that in the investigator's opinion would embarrass glycemic control and completion of the study
• Presence of severe diabetes complications
• Receipt of another investigational drug in the 3 months prior to screening
• Acute psychiatric disorder or exacerbation of chronic psychiatric disorder at screening
• History or presence of drug abuse
• Positive test for addictive substance in urine at screening

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: Insulin Humulin® NPH; Insulin Humulin® NPH twice daily, individually glucose-level based administered doses +/- 1,2 or 3 OADs in stable doses, started before enrollment	Biological: Insulin Humulin® NPH; 4 weeks of glucose-level based dose titration, 24 weeks of treatment with stable doses
Experimental: Insulin Rinsulin® NPH; Insulin Rinsulin® NPH twice daily, individually glucose-level based administered doses +/- 1,2 or 3 OADs in stable doses, started before enrollment	Biological: Insulin Rinsulin® NPH; 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	24 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Hypoglycemic episodes (glucose level < 3.9 mmol/l) frequency	28 weeks (4 + 24 weeks)
Change in BMI from baseline	24 weeks
Occurrence of adverse events	28 weeks (4 + 24 weeks)
Occurrence of Injection Site Reaction	28 weeks (4 + 24 weeks)
Change in HbA1c from baseline	24 weeks
Change in fasting plasma glucose level from baseline	4 weeks
Change in fasting plasma glucose level from baseline	16 weeks
Change in fasting plasma glucose level from baseline	28 weeks
Change in basal insulin dose per body weight (U/kg) from baseline	24 weeks
Change in total basal insulin dose (U) from baseline	24 weeks

Collaborators and Investigators

• Sponsor: Geropharm
• Investigators: Principal Investigator: Olga A Miroshnichenko, PhD, Saint Petersburg State Diagnostic Center № 85

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2017
• Primary Completion (Actual): September 24, 2018
• Study Completion (Actual): September 24, 2018

Study Registration Dates

• First Submitted: July 5, 2019
• First Submitted That Met QC Criteria: July 8, 2019
• First Posted (Actual): July 9, 2019

Study Record Updates

• Last Update Posted (Actual): July 9, 2019
• Last Update Submitted That Met QC Criteria: July 8, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: insulin; diabetes mellitus
• 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; Insulin, Globin Zinc
• Other Study ID Numbers: RINPH-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
• product manufactured in and exported from the U.S.: No