Clinical trial NCT04498884: Comparative Study of the Pharmacokinetics of Rinsulin® Mix 30/70, Suspension for Subcutaneous Administration, 100 IU / ml (OJSC GEROPHARM-Bio, Russia) and Humulin® M3, Suspension for Subcutaneous Administration, 100 IU / ml (Lilly France, France) Using the Euglycemic Hyperinsulinemic Clamp Method
Official title: Double-blinded, Randomized, Comparative, Crossover Study of the Pharmacokinetics of Rinsulin® Mix 30/70, Suspension for Subcutaneous Administration, 100 IU / ml (OJSC GEROPHARM-Bio, Russia) and Humulin® M3, Suspension for Subcutaneous Administration, 100 IU / ml (Lilly France, France) Using the Method of Euglycemic Hyperinsulinemic Clamp on Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Bioequivalence
Keywords: human recombinant insulin
euglycemic hyperinsulinemic clamp
Lead sponsor: Geropharm
Sponsor class: INDUSTRY
First posted: 2020-08-05
Enrollment: 32
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: two-period two-way crossover
Primary purpose: BASIC_SCIENCE

Brief summary: Pharmacokinetics and pharmacodynamics study of 2 formulations of insulin mixtures Rinsulin® Mix 30/70, Suspension for Subcutaneous Administration, 100 IU / ml (OJSC GEROPHARM-Bio, Russia) versus Humulin® M3, Suspension for Subcutaneous Administration, 100 IU / ml (Lilly France, France).

Detailed description: Double-blinded, randomized, comparative, crossover study of comparative pharmacokinetics of Rinsulin® mix 30/70, suspension for subcutaneous administration, 100 IU / ml (OJSC GEROPHARM-Bio, Russia) and Humulin® M3, suspension for subcutaneous administration, 100 IU / ml (Lilly France, France) using hyperinsulinemic euglycemic clamp method on healthy volunteers.

Eligibility criteria: Inclusion Criteria:

* Signed informed consent to participate in the study.
* Men of the Caucasian race with a verified diagnosis "healthy" according to the data of standard clinical, laboratory and instrumental examination methods.
* Age 18-50, inclusive.
* Body mass index 18.5 - 27 kg / m2.
* Volunteers who have sexual contact with fertile women should agree to use barrier methods of contraception while participating in the study (unless they have undergone surgical sterilization). Study Participants must also not become a sperm donor within the specified period.
* Consent to all restrictions imposed during the study.

Exclusion Criteria:

* Acute inflammatory diseases within 3 weeks from the moment of complete recovery to the stage of screening.
* Presence in the family history of the closest relatives cases of verified diagnosis of diabetes mellitus of any type.
* Deviations from the norm of basic vital indicators (heart rate, blood pressure, respiratory rate, body temperature) and ECG from normal values and laboratory values from reference values during screening.
* Fasting plasma glucose\> 6.1 mmol / L at screening.
* HbA1C\> 6% at the time of screening.
* Oral glucose tolerance test - blood glucose level ≥7.8 mmol / L (2 hours after glucose loading) during screening.
* Hard-to-reach veins of the upper extremities, vein thrombosis, history of thrombophlebitis or family history of close relatives, "compromised" veins due to frequent preceding venipuncture.
* Taking medications, phytopreparations, biologically active additives within 14 days before screening.
* Significant blood loss 3 months before screening due to, for example, but not limited to the following points: a. donor blood donation; b. extended surgery or trauma leading to significant blood loss.
* Incomplete recovery from surgery or surgery scheduled while the volunteer is participating in the study.
* Mental, physical and other reasons interferes with adequately assessing behavior and correctly fulfill the conditions of the research protocol incl.:

  1. A history of mental illness;
  2. Current or history (three years before the first administration of the study drug) of narcotic, drug and / or substance abuse. A positive test for the content of drugs in urine during the screening period;
  3. Anamnestic information about alcoholism or intake of more than 10 units. alcohol per week (1 unit of alcohol is equivalent to 0.5 liters of beer, 200 ml of dry wine or 50 ml of spirits). A positive test for alcohol in breath during the screening period;
  4. Nicotine addiction (regular use of tobacco less than 6 months before screening).
* Any chronic diseases, incl. but not limited to positive test results for hepatitis C or hepatitis B, HIV, syphilis at the time of screening, Burdened allergological history.
* Presence of suspicion of an inflammatory disease of the urinary system based on the results of urinalysis during screening.
* Presence of oncological diseases within 5 years before the screening.
* History of organ transplantation (except of corneal transplant performed more than 3 months before the first injection of the study drug).
* Participation in a clinical trial of any drug or experimental medical device within 3 months prior to the first administration of the study drug.
* Any other condition that, in the reasonable opinion of the research physician, makes it difficult for the volunteer to participate in the study.
* History of hypersensitivity to heparin, insulin or any of the excipients of the investigational drugs.

Primary outcomes:
measure: AUC 0-12
timeFrame: -0.5 , 0, every 15 min till 6 h, every 30 min till 11h, every 60 min till 17h, every 120 min till 24h
measure: Cmax
timeFrame: -0.5 , 0, every 15 min till 6 h, every 30 min till 11h, every 60 min till 17h, every 120 min till 24h
measure: GIR 0-12
timeFrame: 1, -0.5, then every 5 min till 10 hour, every 10 min till 12 hour, every 15 min till 24 hour
measure: GIR 0-24
timeFrame: 1, -0.5, then every 5 min till 10 hour, every 10 min till 12 hour, every 15 min till 24 hour
measure: GIR max
timeFrame: 1, -0.5, then every 5 min till 10 hour, every 10 min till 12 hour, every 15 min till 24 hour
measure: tGIRmax
timeFrame: 1, -0.5, then every 5 min till 10 hour, every 10 min till 12 hour, every 15 min till 24 hour
measure: TGIRlag
timeFrame: 1, -0.5, then every 5 min till 10 hour, every 10 min till 12 hour, every 15 min till 24 hour
Secondary outcomes:
measure: AUC 0-2
timeFrame: -0.5 , 0, every 15 min till 6 h, every 30 min till 11h, every 60 min till 17h, every 120 min till 24h
measure: AUC 0-24
timeFrame: -0.5 , 0, every 15 min till 6 h, every 30 min till 11h, every 60 min till 17h, every 120 min till 24h
measure: AUC 0-6
timeFrame: -0.5 , 0, every 15 min till 6 h, every 30 min till 11h, every 60 min till 17h, every 120 min till 24h
measure: AUC 0-∞
timeFrame: -0.5 , 0, every 15 min till 6 h, every 30 min till 11h, every 60 min till 17h, every 120 min till 24h
measure: mean residence time
timeFrame: -0.5 , 0, every 15 min till 6 h, every 30 min till 11h, every 60 min till 17h, every 120 min till 24h
measure: kel
timeFrame: -0.5 , 0, every 15 min till 6 h, every 30 min till 11h, every 60 min till 17h, every 120 min till 24h
measure: Tmax
timeFrame: -0.5 , 0, every 15 min till 6 h, every 30 min till 11h, every 60 min till 17h, every 120 min till 24h
measure: t1/2
timeFrame: -0.5 , 0, every 15 min till 6 h, every 30 min till 11h, every 60 min till 17h, every 120 min till 24h
measure: t50%-early
timeFrame: -0.5 , 0, every 15 min till 6 h, every 30 min till 11h, every 60 min till 17h, every 120 min till 24h
measure: t50%-late
timeFrame: -0.5 , 0, every 15 min till 6 h, every 30 min till 11h, every 60 min till 17h, every 120 min till 24h
measure: ratio Сmax/AUC0-t
timeFrame: -0.5 , 0, every 15 min till 6 h, every 30 min till 11h, every 60 min till 17h, every 120 min till 24h
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: "National Medical Research Center of Endocrinology" of the Ministry of Health of the Russian Federation
city: Saint-Petersburg
country: Russian Federation
facility: National Medical Research Center in name of V.A. Almazov " of the Ministry of Health of the Russian Federation
city: St. Petersburg
country: Russian Federation
facility: LLC "BioEk", Russian Federation
Study officials:
References: