Efficacy and Safety of GP40081 Сompared to NovoMix® 30 FlexPen® in Type 2 Diabetes Mellitus Patients

An Open-label, Randomized, Multi-center, Parallel-group Clinical Trial Comparing the Efficacy and Safety of GP40081 (OOO "GEROPHARM", Russia) Compared to NovoMix® 30 FlexPen® (Novo Nordisk A/S, Denmark) in Type 2 Diabetes Mellitus Patients

This trial is a multi-center, open-label, randomized, parallel group trial in adult patients with T2DM comparing the efficacy and safety of GP40081 (insulin asapart mix 30, GEROPHARM) with that of NovoMix® 30 FlexPen®.

Study Overview

• Status: Unknown
• Conditions: Diabetes Mellitus, Type 2; Diabetes Mellitus
• Intervention / Treatment: Drug: GP40081; Drug: NovoMix 30

• Study Type: Interventional
• Enrollment (Anticipated): 264
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Arkhangel'sk, Russian Federation, 163045
    • Arkhangelsk Regional Clinical Hospital
  • Kazan, Russian Federation, 420073
    • Kazan Endocrinology Dispensary
  • Krasnoyarsk, Russian Federation, 660022
    • Krasnoyarsk State Medical University named after Professor V.F. Voino-Yasenetsky
  • Petrozavodsk, Russian Federation, 185000
    • V.A. Baranov Republic Hospital
  • Saint Petersburg, Russian Federation, 194354
    • City Diagnostic Center № 1
  • Saint Petersburg, Russian Federation, 194354
    • City Hospital № 2
  • Saint Petersburg, Russian Federation, 194358
    • City Polyclinic № 117
  • Saint Petersburg, Russian Federation, 195197
    • EosMed
  • Saint Petersburg, Russian Federation, 196084
    • Institute of Medical Research
  • Saint Petersburg, Russian Federation, 196143
    • Research Center Eco-Safety
  • Saint Petersburg, Russian Federation, 197341
    • Almazov National Medical Research Centre
  • Saint Petersburg, Russian Federation, 199106
    • Pokrovskaya Municipal Hospital
  • Samara, Russian Federation, 443067
    • Diabetes Center
  • Volgograd, Russian Federation, 400081
    • Volgograd Region Clinical Hospital №1

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
• Diabetes mellitus type 2 for at least 6 months before the screening (WHO criteria 1999-2013).
• Glycated haemoglobin (HbA1c) level of 7.6 to 12.0 % at screening (both values inclusive).
• Indications for exogenous insulin therapy.
• Body mass index (BMI) of 18.5 to 40 kg/m2 at screening (both values inclusive).
• Insulin-naive patients or prior insulin therapy at least 6 months before randomization.
• The subject is able and willing to comply with the requirements of the study protocol

Exclusion Criteria:

• Contraindication to the use of insulin aspart 30 mix.
• 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 severe hypoglycemia for 6 months before the screening.
• History of severe hyperglycemia for 6 months before the screening.
• Bariatric surgery for 12 months to screening.
• Glucagon-like peptide-1 (GLP-1)-based therapies for 8 weeks to screening.
• Insulin resistance over 1.5 U/kg insulin pro day.
• Change INN of insulin for 6 months before the randomisation.
• History of treatment any experimental drugs or medical devices for 3 months before the randomisation.
• Presence of severe diabetes complications.
• Night work.
• History of administration of glucocorticoids (14 days or more) for 1 year before the screening.
• Administration of any immunosuppressive drugs (Cyclosporinum, Methotrexate, Rituximab, etc.).
• History of vaccination for 6 months before the randomisation.
• History of autoimmune disease, except vitiligo and controlled autoimmune polyglandular syndrome (APS) types 1-3, except vetiligo and Hashimoto's thyroiditis.
• Pregnant and breast-feeding women.
• Deviation of the laboratory results conducted during the screening: Hemoglobin value < 9,0 g/dl; Hematocrit value < 30 %; ALT and AST value > 2 folds or ALT or AST value > 3 folds as high as maximal normal value; Serum bilirubin value > 2 folds as high as maximal normal value (except Gilbert's syndrome).
• History of haematological disorders that can affect the reliability of HbA1c estimation (haemoglobinopathies, hemolytic anaemia, etc.).
• Serological evidence of human immunodeficiency virus (HIV), hepatitis B (HbSAg), hepatitis C (HCVAb) or syphilis (Treponema pallidum) antibodies at the screening.
• Acute inflammation disease for 3 weeks before the screening.
• History of unstable angina, myocardial infarction, severe arrhythmia, heart failure III or IV NYHA for 1 year before the screening.
• History of stroke or TIA for 6 months before the screening.
• Serious blood loss for 3 months before the screening (blood donation, surgery procedure, etc.).
• The inability of the patient to assess their condition because of mental or physical disorders.
• History of drug, alcohol abuse for 3 years before the screening.
• History of oncology disorders for 5 years before the screening.
• History of transplantation, except 3 months after a corneal transplant.
• History or presence of a medical condition or disease that in the investigator's opinion would embarrass glycemic control and completion of the study

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
Experimental: GP40081; Subcutaneous (SC), up to Week 26	Drug: GP40081; 1 ml of the GP40081 contains 100 units soluble insulin aspart/protamine-crystallised insulin aspart in the ratio 30/70. Insulin aspart 30 mix is self-administered drug by SC injection 1-3 times per day before meal intake.; Other Names: Insulin aspart 30 mix
Active Comparator: NovoMix® 30 FlexPen®; Subcutaneous (SC), up to Week 26	Drug: NovoMix 30; 1 ml of the NovoMix 30 contains 100 units soluble insulin aspart/protamine-crystallised insulin aspart in the ratio 30/70. Insulin aspart 30 mix is self-administered drug by SC injection 1-3 times per day before meal intake.; Other Names: Insulin aspart 30 mix

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycated hemoglobin	Change in HbA1c 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
Fasting Plasma Glucose Level	Change in fasting plasma glucose level from baseline	26 weeks
Seven-Point Glucose Testing	Change in seven-point glucose testing results from baseline	22 weeks
Total Insulin Dose	Change in total insulin dose per body weight (U/kg) from baseline	22 weeks
Body Mass Index	Change in BMI from baseline	26 weeks
Treatment Satisfaction: The Diabetes Treatment Satisfaction Questionnaire	Change in treatment satisfaction from baseline. Questions 1, 4, 5, 6, 7 and 8 assesses treatment satisfaction (summed these 6 questions). Questions 2 and 3 assess the burden from hyper- and hypoglycemia. DTSQ is The Diabetes Treatment Satisfaction Questionnaire, scored from 0-36 points with higher scores indicating better satisfaction.	26 weeks
Achievement of Glycated Hemoglobin Goals	The frequency of achievement glycated hemoglobin goals	26 weeks
Achievement of Glycated Hemoglobin < 7%	The frequency of achievement glycated hemoglobin < 7% ( 7% inclusive)	26 weeks

Collaborators and Investigators

• Sponsor: Geropharm

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2020
• Primary Completion (Anticipated): September 30, 2020
• Study Completion (Anticipated): December 25, 2020

Study Registration Dates

• First Submitted: January 9, 2020
• First Submitted That Met QC Criteria: January 10, 2020
• First Posted (Actual): January 13, 2020

Study Record Updates

• Last Update Posted (Actual): April 15, 2020
• Last Update Submitted That Met QC Criteria: April 14, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• 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; Insulin Aspart; Insulin, Long-Acting; Insulin degludec, insulin aspart drug combination; Insulin aspart, insulin aspart protamine drug combination 30:70
• Other Study ID Numbers: GP40081-P4-31

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