<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04501250</url>
  </required_header>
  <id_info>
    <org_study_id>RINCL-NPH</org_study_id>
    <nct_id>NCT04501250</nct_id>
  </id_info>
  <brief_title>Comparative Study of Rinsulin® NPH, Suspension for Subcutaneous Administration, 100 IU/ml (GEROPHARM LLC, Russia) and Humulin® NPH, Suspension for Subcutaneous Administration, 100 IU/ml (Lilly France, France) Using the Euglycemic Hyperinsulinemic Clamp Method</brief_title>
  <official_title>A Double-blinded, Randomized, Comparative, Crossover Pharmacokinetics Study of Rinsulin® NPH, Suspension for Subcutaneous Administration, 100 IU/ml (GEROPHARM LLC, Russia) and Humulin® NPH, Suspension for Subcutaneous Administration, 100 IU/ml (Lilly France, France) Using Method of Euglycemic Hyperinsulinemic Clamp on Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Geropharm</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Geropharm</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Сomparative pharmacokinetic study of Rinsulin® NPH, suspension for subcutaneous&#xD;
      administration, 100 IU/ml (GEROPHARM LLC, Russia) and Humulin® NPH, suspension for&#xD;
      subcutaneous administration, 100 IU/ml (Lilly France, France) using the euglycemic&#xD;
      hyperinsulinemic clamp.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A double-blinded, randomized, comparative, crossover pharmacokinetics study of Rinsulin® NPH,&#xD;
      suspension for subcutaneous administration, 100 IU/ml (GEROPHARM LLC, Russia) and Humulin®&#xD;
      NPH, suspension for subcutaneous administration, 100 IU/ml (Lilly France, France) using&#xD;
      method of euglycemic hyperinsulinemic clamp on healthy volunteers&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 23, 2017</start_date>
  <completion_date type="Actual">May 21, 2018</completion_date>
  <primary_completion_date type="Actual">January 1, 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>Crossover Assignment two-way crossover</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>A double-blinded</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Смах</measure>
    <time_frame>- 1 , -0.5 , 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20, 22, 24 hours</time_frame>
    <description>Test Drug Observed Maximum Plasma Concentration (Cmax)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC 0-12</measure>
    <time_frame>- 1 , -0.5 , 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20, 22, 24 hours</time_frame>
    <description>Total area under the curve &quot;drug concentration - time&quot; in the time interval from 0 to 12 h</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC GIR 0-12</measure>
    <time_frame>-2, -1.5, 1, -0.5, then every 5 min till 10 hour, every 10 min till 12 hour, every 15 min till 24 hour</time_frame>
    <description>Total area under the curve &quot;glucose infusion rate - time&quot; in the time interval from 0 to 12 h</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC GIR 0-24</measure>
    <time_frame>-2, -1.5, 1, -0.5, then every 5 min till 10 hour, every 10 min till 12 hour, every 15 min till 24 hour</time_frame>
    <description>Total area under the curve &quot;glucose infusion rate - time&quot; in the time interval from 0 to 24 h</description>
  </primary_outcome>
  <primary_outcome>
    <measure>GIRmax</measure>
    <time_frame>-2, -1.5, 1, -0.5, then every 5 min till 10 hour, every 10 min till 12 hour, every 15 min till 24 hour</time_frame>
    <description>Maximum glucose infusion rate over the study period</description>
  </primary_outcome>
  <primary_outcome>
    <measure>tGIRmax</measure>
    <time_frame>-2, -1.5, 1, -0.5, then every 5 min till 10 hour, every 10 min till 12 hour, every 15 min till 24 hour</time_frame>
    <description>Time to reach maximum glucose infusion rate</description>
  </primary_outcome>
  <primary_outcome>
    <measure>tGIRlag</measure>
    <time_frame>-2, -1.5, 1, -0.5, then every 5 min till 10 hour, every 10 min till 12 hour, every 15 min till 24 hour</time_frame>
    <description>Time between the drug administration and the onset of action</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>AUC 0-2</measure>
    <time_frame>- 1 , -0.5 , 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20, 22, 24 hours</time_frame>
    <description>Total area under the curve &quot;drug concentration - time&quot; in the time interval from 0 to 2 h</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC 0-6</measure>
    <time_frame>- 1 , -0.5 , 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20, 22, 24 hours</time_frame>
    <description>Total area under the curve &quot;drug concentration - time&quot; in the time interval from 0 to 6 h</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC 0-24</measure>
    <time_frame>- 1 , -0.5 , 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20, 22, 24 hours</time_frame>
    <description>Total area under the curve &quot;drug concentration - time&quot; in the time interval from 0 to 24 h</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC 0-∞</measure>
    <time_frame>- 1 , -0.5 , 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20, 22, 24 hours</time_frame>
    <description>Total area under the curve &quot;drug concentration - time&quot; in the time interval from 0 to ∞</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax</measure>
    <time_frame>- 1 , -0.5 , 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20, 22, 24 hours</time_frame>
    <description>Time to reach test drug Maximum Plasma Concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T1/2</measure>
    <time_frame>- 1 , -0.5 , 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20, 22, 24 hours</time_frame>
    <description>Half-life of a drug tested</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">52</enrollment>
  <condition>Pharmacokinetics</condition>
  <condition>Bioequivalence</condition>
  <arm_group>
    <arm_group_label>Rinsulin® NPH</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single subcutaneous administration of Insulin at a dose 0.4 IU / kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Humulin® NPH</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Single subcutaneous administration of Insulin at a dose 0.4 IU / kg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rinsulin NPH</intervention_name>
    <description>subcutaneous injection at a dose of 0.4 IU/kg</description>
    <arm_group_label>Humulin® NPH</arm_group_label>
    <arm_group_label>Rinsulin® NPH</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Humulin NPH</intervention_name>
    <description>subcutaneous injection at a dose of 0.4 IU/kg</description>
    <arm_group_label>Humulin® NPH</arm_group_label>
    <arm_group_label>Rinsulin® NPH</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed informed consent to participate in the study.&#xD;
&#xD;
          -  Men of the Caucasian race with a verified diagnosis &quot;healthy&quot; according to the data of&#xD;
             standard clinical, laboratory and instrumental examination methods.&#xD;
&#xD;
          -  Age 18-50, inclusive.&#xD;
&#xD;
          -  Body mass index 18.5 - 27 kg / m2.&#xD;
&#xD;
          -  Volunteers who have sexual contact with fertile women should agree to use barrier&#xD;
             methods of contraception while participating in the study (unless they have undergone&#xD;
             surgical sterilization). Study Participants must also not become a sperm donor within&#xD;
             the specified period.&#xD;
&#xD;
          -  Consent to all restrictions imposed during the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Acute inflammatory diseases within 3 weeks from the moment of complete recovery to the&#xD;
             stage of screening.&#xD;
&#xD;
          -  Presence of episodes of hypoglycemia in the history of the volunteer&#xD;
&#xD;
          -  Presence in the family history of the closest relatives cases of verified diagnosis of&#xD;
             diabetes mellitus of any type.&#xD;
&#xD;
          -  Deviations from the norm of basic vital indicators (heart rate, blood pressure,&#xD;
             respiratory rate, body temperature) and ECG from normal values and laboratory values&#xD;
             from reference values during screening.&#xD;
&#xD;
          -  Fasting plasma glucose&gt; 6.1 mmol / L at screening.&#xD;
&#xD;
          -  HbA1C&gt; 6% at the time of screening.&#xD;
&#xD;
          -  Oral glucose tolerance test - blood glucose level ≥7.8 mmol / L (2 hours after glucose&#xD;
             loading) during screening.&#xD;
&#xD;
          -  Hard-to-reach veins of the upper extremities, vein thrombosis, history of&#xD;
             thrombophlebitis or family history of close relatives, &quot;compromised&quot; veins due to&#xD;
             frequent preceding venipuncture.&#xD;
&#xD;
          -  Taking medications, phytopreparations, biologically active additives within 14 days&#xD;
             before screening.&#xD;
&#xD;
          -  Significant blood loss 3 months before screening due to, for example, but not limited&#xD;
             to the following points: a. donor blood donation; b. extended surgery or trauma&#xD;
             leading to significant blood loss.&#xD;
&#xD;
          -  Incomplete recovery from surgery or surgery scheduled while the volunteer is&#xD;
             participating in the study.&#xD;
&#xD;
          -  Mental, physical and other reasons interferes with adequately assessing behavior and&#xD;
             correctly fulfill the conditions of the research protocol (incl. a history of mental&#xD;
             illness).&#xD;
&#xD;
          -  Presence or history (three years before the the study drug) of narcotic, drug and / or&#xD;
             substance abuse.&#xD;
&#xD;
          -  Positive test for the content of narcotic drugs in urine during the screening period.&#xD;
&#xD;
          -  Anamnestic information about alcoholism or taking more than 10 units. alcohol per week&#xD;
             (1 unit of alcohol is equivalent to 0.5 liters of beer, 200 ml of dry wine or 50 ml of&#xD;
             spirits).&#xD;
&#xD;
          -  Positive test for alcohol in breath during screening.&#xD;
&#xD;
          -  Nicotine addiction (regular use of tobacco less than 6 months before screening).&#xD;
&#xD;
          -  Any chronic diseases, incl. but not limited to positive test results for hepatitis C&#xD;
             or hepatitis B, HIV, syphilis at the time of screening.&#xD;
&#xD;
          -  Burdened allergological history.&#xD;
&#xD;
          -  presence of suspicion of an inflammatory disease of the urinary system based on the&#xD;
             results of urinalysis during screening.&#xD;
&#xD;
          -  Presence of oncological diseases within 5 years before the screening.&#xD;
&#xD;
          -  History of organ transplantation (except of corneal transplant performed more than 3&#xD;
             months before the first injection of the study drug).&#xD;
&#xD;
          -  Participation in a clinical trial of any drug or experimental medical device within 3&#xD;
             months prior to the first administration of the study drug.&#xD;
&#xD;
          -  Any other condition that, in the reasonable opinion of the research physician, makes&#xD;
             it difficult for the volunteer to participate in the study.&#xD;
&#xD;
          -  History of hypersensitivity to heparin, insulin or any of the excipients of the&#xD;
             investigational drugs.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sergei Mr Noskov, AP of medicine</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yaroslavl City Clinical Hospital No. 3</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Yarosslavl Clinical Hospital #3</name>
      <address>
        <city>Yaroslavl</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>August 3, 2020</study_first_submitted>
  <study_first_submitted_qc>August 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 6, 2020</study_first_posted>
  <last_update_submitted>August 3, 2020</last_update_submitted>
  <last_update_submitted_qc>August 3, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 6, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>human recombinant insulin</keyword>
  <keyword>euglycemic hyperinsulinemic clamp</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin</mesh_term>
    <mesh_term>Insulin, Globin Zinc</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04501250
org study id: RINCL-NPH
nct id: NCT04501250
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Сomparative pharmacokinetic study of Rinsulin® NPH, suspension for subcutaneous
      administration, 100 IU/ml (GEROPHARM LLC, Russia) and Humulin® NPH, suspension for
      subcutaneous administration, 100 IU/ml (Lilly France, France) using the euglycemic
      hyperinsulinemic clamp.
A double-blinded, randomized, comparative, crossover pharmacokinetics study of Rinsulin® NPH,
      suspension for subcutaneous administration, 100 IU/ml (GEROPHARM LLC, Russia) and Humulin®
      NPH, suspension for subcutaneous administration, 100 IU/ml (Lilly France, France) using
      method of euglycemic hyperinsulinemic clamp on healthy volunteers
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Crossover Assignment two-way crossover
primary purpose: Basic Science
masking: Double (Participant, Investigator)
masking description: A double-blinded
measure: Смах
time frame: - 1 , -0.5 , 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20, 22, 24 hours
description: Test Drug Observed Maximum Plasma Concentration (Cmax)
measure: AUC 0-12
time frame: - 1 , -0.5 , 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20, 22, 24 hours
description: Total area under the curve "drug concentration - time" in the time interval from 0 to 12 h
measure: AUC GIR 0-12
time frame: -2, -1.5, 1, -0.5, then every 5 min till 10 hour, every 10 min till 12 hour, every 15 min till 24 hour
description: Total area under the curve "glucose infusion rate - time" in the time interval from 0 to 12 h
measure: AUC GIR 0-24
time frame: -2, -1.5, 1, -0.5, then every 5 min till 10 hour, every 10 min till 12 hour, every 15 min till 24 hour
description: Total area under the curve "glucose infusion rate - time" in the time interval from 0 to 24 h
measure: GIRmax
time frame: -2, -1.5, 1, -0.5, then every 5 min till 10 hour, every 10 min till 12 hour, every 15 min till 24 hour
description: Maximum glucose infusion rate over the study period
measure: tGIRmax
time frame: -2, -1.5, 1, -0.5, then every 5 min till 10 hour, every 10 min till 12 hour, every 15 min till 24 hour
description: Time to reach maximum glucose infusion rate
measure: tGIRlag
time frame: -2, -1.5, 1, -0.5, then every 5 min till 10 hour, every 10 min till 12 hour, every 15 min till 24 hour
description: Time between the drug administration and the onset of action
measure: AUC 0-2
time frame: - 1 , -0.5 , 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20, 22, 24 hours
description: Total area under the curve "drug concentration - time" in the time interval from 0 to 2 h
measure: AUC 0-6
time frame: - 1 , -0.5 , 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20, 22, 24 hours
description: Total area under the curve "drug concentration - time" in the time interval from 0 to 6 h
measure: AUC 0-24
time frame: - 1 , -0.5 , 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20, 22, 24 hours
description: Total area under the curve "drug concentration - time" in the time interval from 0 to 24 h
measure: AUC 0-∞
time frame: - 1 , -0.5 , 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20, 22, 24 hours
description: Total area under the curve "drug concentration - time" in the time interval from 0 to ∞
measure: Tmax
time frame: - 1 , -0.5 , 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20, 22, 24 hours
description: Time to reach test drug Maximum Plasma Concentration
measure: T1/2
time frame: - 1 , -0.5 , 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20, 22, 24 hours
description: Half-life of a drug tested
arm group label: Rinsulin® NPH
arm group type: Experimental
description: Single subcutaneous administration of Insulin at a dose 0.4 IU / kg
arm group label: Humulin® NPH
arm group type: Active Comparator
description: Single subcutaneous administration of Insulin at a dose 0.4 IU / kg
intervention type: Drug
intervention name: Rinsulin NPH
description: subcutaneous injection at a dose of 0.4 IU/kg
arm group label: Humulin® NPH
arm group label: Rinsulin® NPH
intervention type: Drug
intervention name: Humulin NPH
description: subcutaneous injection at a dose of 0.4 IU/kg
arm group label: Humulin® NPH
arm group label: Rinsulin® NPH
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Sergei Mr Noskov, AP of medicine
role: Principal Investigator
affiliation: Yaroslavl City Clinical Hospital No. 3
facility: 
country: Russian Federation
responsible party type: Sponsor
mesh term: Insulin
mesh term: Insulin, Globin Zinc
sharing ipd: No