<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/NCT03028285</url>
  </required_header>
  <id_info>
    <org_study_id>UNI-I-2015</org_study_id>
    <nct_id>NCT03028285</nct_id>
  </id_info>
  <brief_title>Study of Safety and Tolerability of UNIFUZOL (Solution for Infusions) in Healthy Volunteers</brief_title>
  <official_title>Open Randomized Study of the Safety, Tolerability, and Pharmacokinetic Parameters of UNIFUZOL® (Solution for Infusions, 1.4%, Manufactured by &quot;NTFF&quot;POLYSAN &quot; Ltd.,Russia) in Healthy Volunteers at Different Rates of Administration (Phase I)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>POLYSAN Scientific &amp; Technological Pharmaceutical Company</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>POLYSAN Scientific &amp; Technological Pharmaceutical Company</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Unifusol (R) is a solution of arginine sodium succinate for intravenous infusions. Its&#xD;
      effects include vasodilation, protection of inner layer of blood vessels and improvement of&#xD;
      blood viscosity. The present phase I study is aimed to evaluate the safety and tolerability&#xD;
      of Unifusol infusions in healthy volunteers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Unifuzol, solution for infusions,(&quot;NTFF POLYSAN&quot; Ltd., Russia) contains succinic acid and&#xD;
      arginine as active ingredients; it has demonstrated cardioprotective, anti-ischemic,&#xD;
      endothelial protective and fibrinolytic activity in pre-clinical studies and is considered&#xD;
      for clinical trials in peripheral vascular disease.&#xD;
&#xD;
      The primary aim of the present Phase I study is to assess safety and tolerability of Unifusol&#xD;
      (1.4% solution for infusions) at different infusion rates in healthy volunteers.&#xD;
&#xD;
      Study objectives:&#xD;
&#xD;
        1. Assess the safety parameters (vital signs, the incidence of AEs, SAEs, laboratory&#xD;
           abnormalities) during infusion of Unifusol (1.4% solution for infusions) in healthy&#xD;
           volunteers at different infusion rates.&#xD;
&#xD;
             -  administration of a single infusion of 250 ml at a rate of 3 ml / min.&#xD;
&#xD;
             -  administration of a single infusion of 250 ml at a rate of 4.5 ml / min&#xD;
&#xD;
             -  administration of a single infusion of 500 ml at a rate of 4.5 ml / min&#xD;
&#xD;
        2. Study the pharmacokinetics parameters of the active components of the Unifusol (succinic&#xD;
           acid and arginine) in healthy volunteers after single infusion at a dose of 250 ml at a&#xD;
           rate of 4.5 ml / min.&#xD;
&#xD;
      Study methods:&#xD;
&#xD;
        1. Determination of pharmacokinetic parameters of succinic acid administered at a single&#xD;
           Unifusol infusion dose 250 ml at a rate of 4.5 ml / min (AUC, Cmax, Tmax, T1 / 2);&#xD;
&#xD;
        2. Determination of pharmacokinetic parameters of arginine after a single Unifusol infusion&#xD;
           at a dose 250 ml at a rate of 4.5 ml / min (AUC, Cmax, Tmax, T1 / 2);&#xD;
&#xD;
        3. Determination of individual variations of the pharmacokinetic parameters of succinic&#xD;
           acid and arginine in healthy volunteers;&#xD;
&#xD;
        4. Identification of significant gender differences in the pharmacokinetics of the active&#xD;
           ingredients of Unifusol (succinic acid and arginine) in healthy volunteers;&#xD;
&#xD;
        5. Determination of the number of compartments in the pharmacokinetic model which will be&#xD;
           most appropriate to the measured concentrations after a single infusion (single-chamber,&#xD;
           two-chamber or three-chamber pharmacokinetic model).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 15, 2016</start_date>
  <completion_date type="Actual">January 26, 2017</completion_date>
  <primary_completion_date type="Actual">January 19, 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of treatment-related adverse events, derangements of vital signs, and laboratory abnormalities</measure>
    <time_frame>18-26 days</time_frame>
    <description>Absence of vital disorders, SAEs, laboratory abnormalities, and the incidence of AEs</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration of arginine versus time curve</measure>
    <time_frame>6 hours</time_frame>
    <description>AUC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration of succinic acid versus time curve</measure>
    <time_frame>6 hours</time_frame>
    <description>AUC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak Plasma Concentration of arginine</measure>
    <time_frame>6 hours</time_frame>
    <description>Cmax</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak Plasma Concentration of succinic acid</measure>
    <time_frame>6 hours</time_frame>
    <description>Cmax</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to peak Plasma Concentration of arginine</measure>
    <time_frame>6 hours</time_frame>
    <description>Tmax</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to peak Plasma Concentration of succinic acid</measure>
    <time_frame>6 hours</time_frame>
    <description>Tmax</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>Peripheral Vascular Disease</condition>
  <arm_group>
    <arm_group_label>Unifusol 250 ml IV, 3 ml/mil</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Twelve healthy volunteers will receive the experimental drug (arginine sodium succinate 1.4% solution; Unifusol) intravenously at a dose 250 ml and infusion rate 3 ml/min.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Unifusol 250 ml IV, 4.5 ml/min</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Twenty-four healthy volunteers will receive arginine sodium succinate 1.4% solution (Unifusol) intravenously at a dose 250 ml and infusion rate 4.5 ml/min</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Unifusol 500 ml IV, 4.5 ml/min</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Twelve healthy volunteers will receive arginine sodium succinate 1.4% solution (Unifusol) intravenously at a dose 500 ml and infusion rate 4.5 ml/min</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>arginine sodium succinate</intervention_name>
    <description>Healthy volunteers will receive the experimental drug (arginine sodium succinate 1.4% solution; Unifusol) intravenously at 3 different combinations of dose and infusion rate under the close monitoring of vital signs and other safety parameters.</description>
    <arm_group_label>Unifusol 250 ml IV, 3 ml/mil</arm_group_label>
    <arm_group_label>Unifusol 250 ml IV, 4.5 ml/min</arm_group_label>
    <arm_group_label>Unifusol 500 ml IV, 4.5 ml/min</arm_group_label>
    <other_name>Unifusol</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy condition, as verified by standard clinical, laboratory and instrumental&#xD;
             methods of examination.&#xD;
&#xD;
          2. The body mass index (BMI) of 18.5 to 30 and a body weight above 50 kg.&#xD;
&#xD;
          3. Signed informed consent.&#xD;
&#xD;
          4. For men - consent to use the double-barrier contraceptive method during the course of&#xD;
             the study, and for 90 days after the study completion.&#xD;
&#xD;
          5. For women - negative pregnancy test, absence of lactation, and consent to use the&#xD;
             double-barrier method of contraception during the study and for 90 days after study&#xD;
             completion. In the case of hormonal contraceptive use, the intake must be canceled no&#xD;
             later than 2 months before the start of the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Intolerance or hypersensitivity to the components of the study drug.&#xD;
&#xD;
          2. Chronic diseases of the cardiovascular, bronchopulmonary (including bronchospastic&#xD;
             disease), neuroendocrine system, chronic diseases of the gastrointestinal tract,&#xD;
             liver, kidneys, blood, immune system, mental illness or substance abuse, or a history&#xD;
             of alcoholism.&#xD;
&#xD;
          3. Acute infectious diseases within 4 weeks before the start of the study.&#xD;
&#xD;
          4. Any abnormalities of the laboratory findings before inclusion.&#xD;
&#xD;
          5. The presence of mental disorders, or the history of mental illness.\&#xD;
&#xD;
          6. Intake of medications and/or nutritional supplements for 14 days or 5 half-lives&#xD;
             (whichever is longer) prior to the first dose of study drug, or using drugs that have&#xD;
             a significant effect on hemodynamics, liver function, etc. (for instance,&#xD;
             barbiturates, omeprazole, cimetidine) for 2 months prior to the first dose of study&#xD;
             medication. Receiving herbal medicines and herbal supplements during the 28 days&#xD;
             before the first dose of study medication.&#xD;
&#xD;
          7. Hormonal methods of contraception with systemic effects (including oral and&#xD;
             transdermal contraceptives, injectable progesterone, subcutaneous implants with a&#xD;
             progestin intrauterine device with progesterone release) and hormone replacement&#xD;
             therapy within 60 days prior to the first dose of study medication.&#xD;
&#xD;
          8. The injection of any drug, depot (slow release) or the use of drug implant within 3&#xD;
             months prior to the administration of the study drug.&#xD;
&#xD;
          9. Abnormalities of vital signs: systolic blood pressure below 100 mm Hg or higher than&#xD;
             130 mm Hg; diastolic blood pressure below 60 mmHg or above 90 mm Hg; heart rate below&#xD;
             60 beats / min or above 90 beats / min.&#xD;
&#xD;
         10. Data of 12-lead ECG demonstrating the QTc interval&gt; 450 msec or the QRS&gt; 120 ms on&#xD;
             screening visit.&#xD;
&#xD;
         11. Blood donation (450 ml of blood or more) in less than 3 months prior to inclusion.&#xD;
&#xD;
         12. Participation in clinical trials of drugs in 3 months before inclusion.&#xD;
&#xD;
         13. The regular consumption of more than 5 units of alcohol per week (each unit is equal&#xD;
             to 30 ml of ethanol or 325 ml of beer) or the history of alcoholism, drug addiction,&#xD;
             drug abuse.&#xD;
&#xD;
         14. A positive test for alcohol in the exhaled air.&#xD;
&#xD;
         15. Smoking more than 10 cigarettes per day.&#xD;
&#xD;
         16. A positive urine test for drugs, such as amphetamine, marijuana, morphine, cocaine and&#xD;
             methamphetamine, and tricyclic antidepressants, as revealed in urine by immunoassay&#xD;
             analysis.&#xD;
&#xD;
         17. The positive results of the analyzes for hepatitis B or C, HIV, and/or syphilis.&#xD;
&#xD;
         18. Unwilling or unable to give up alcohol intake, smoking and excessive exercise 48 hours&#xD;
             prior to study drug administration and up to 96 hours after administration of the&#xD;
             drug, as well as food and beverages containing methylxanthines and grapefruit /&#xD;
             grapefruit juice from the day prior to the screening visit and at follow-up.&#xD;
&#xD;
         19. Compliance to a special diet (eg. vegetarian) or lifestyle (including night work and&#xD;
             extreme exercise, such as sports or weight lifting) that may interfere with the study&#xD;
             procedures.&#xD;
&#xD;
         20. Planning inpatient treatment of the volunteer within one month after the first&#xD;
             injection of the study drug.&#xD;
&#xD;
         21. Lack of intention to comply with the study regimen.&#xD;
&#xD;
         22. Obvious or probable inability of volunteer, according to the judgement of the&#xD;
             researcher, to understand and evaluate information about the study and consciously&#xD;
             sign the informed consent form, in particular with respect to the expected risks and&#xD;
             possible discomfort.&#xD;
&#xD;
         23. Expected problem with the placement of venous catheters or performing vein puncture.&#xD;
&#xD;
         24. Pregnancy or breast-feeding; unwillingness or inability of a woman of childbearing age&#xD;
             to use acceptable methods of barrier contraception, according to the protocol,&#xD;
             starting at least 14 days prior to the first dose of study medication and for 90 days&#xD;
             after study completion.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Vasily B Vasilyuk, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Research Center for Eco-safety</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinical diagnostic laboratory of City Clinical Hospital named after I.V.Davydovsky</name>
      <address>
        <city>Moscow</city>
        <zip>109240</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Center for Eco-safety, Ltd.</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>196143</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>January 16, 2017</study_first_submitted>
  <study_first_submitted_qc>January 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 23, 2017</study_first_posted>
  <last_update_submitted>July 10, 2020</last_update_submitted>
  <last_update_submitted_qc>July 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 14, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>succinate</keyword>
  <keyword>arginine</keyword>
  <keyword>vasodilation</keyword>
  <keyword>peripheral vascular disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vascular Diseases</mesh_term>
    <mesh_term>Peripheral Vascular Diseases</mesh_term>
    <mesh_term>Peripheral Arterial Disease</mesh_term>
  </condition_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/NCT03028285
org study id: UNI-I-2015
nct id: NCT03028285
lead sponsor: 
has dmc: No
Unifusol (R) is a solution of arginine sodium succinate for intravenous infusions. Its
      effects include vasodilation, protection of inner layer of blood vessels and improvement of
      blood viscosity. The present phase I study is aimed to evaluate the safety and tolerability
      of Unifusol infusions in healthy volunteers.
Unifuzol, solution for infusions,("NTFF POLYSAN" Ltd., Russia) contains succinic acid and
      arginine as active ingredients; it has demonstrated cardioprotective, anti-ischemic,
      endothelial protective and fibrinolytic activity in pre-clinical studies and is considered
      for clinical trials in peripheral vascular disease.

      The primary aim of the present Phase I study is to assess safety and tolerability of Unifusol
      (1.4% solution for infusions) at different infusion rates in healthy volunteers.

      Study objectives:

        1. Assess the safety parameters (vital signs, the incidence of AEs, SAEs, laboratory
           abnormalities) during infusion of Unifusol (1.4% solution for infusions) in healthy
           volunteers at different infusion rates.

             -  administration of a single infusion of 250 ml at a rate of 3 ml / min.

             -  administration of a single infusion of 250 ml at a rate of 4.5 ml / min

             -  administration of a single infusion of 500 ml at a rate of 4.5 ml / min

        2. Study the pharmacokinetics parameters of the active components of the Unifusol (succinic
           acid and arginine) in healthy volunteers after single infusion at a dose of 250 ml at a
           rate of 4.5 ml / min.

      Study methods:

        1. Determination of pharmacokinetic parameters of succinic acid administered at a single
           Unifusol infusion dose 250 ml at a rate of 4.5 ml / min (AUC, Cmax, Tmax, T1 / 2);

        2. Determination of pharmacokinetic parameters of arginine after a single Unifusol infusion
           at a dose 250 ml at a rate of 4.5 ml / min (AUC, Cmax, Tmax, T1 / 2);

        3. Determination of individual variations of the pharmacokinetic parameters of succinic
           acid and arginine in healthy volunteers;

        4. Identification of significant gender differences in the pharmacokinetics of the active
           ingredients of Unifusol (succinic acid and arginine) in healthy volunteers;

        5. Determination of the number of compartments in the pharmacokinetic model which will be
           most appropriate to the measured concentrations after a single infusion (single-chamber,
           two-chamber or three-chamber pharmacokinetic model).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of treatment-related adverse events, derangements of vital signs, and laboratory abnormalities
time frame: 18-26 days
description: Absence of vital disorders, SAEs, laboratory abnormalities, and the incidence of AEs
measure: Area under the plasma concentration of arginine versus time curve
time frame: 6 hours
description: AUC
measure: Area under the plasma concentration of succinic acid versus time curve
time frame: 6 hours
description: AUC
measure: Peak Plasma Concentration of arginine
time frame: 6 hours
description: Cmax
measure: Peak Plasma Concentration of succinic acid
time frame: 6 hours
description: Cmax
measure: Time to peak Plasma Concentration of arginine
time frame: 6 hours
description: Tmax
measure: Time to peak Plasma Concentration of succinic acid
time frame: 6 hours
description: Tmax
arm group label: Unifusol 250 ml IV, 3 ml/mil
arm group type: Experimental
description: Twelve healthy volunteers will receive the experimental drug (arginine sodium succinate 1.4% solution; Unifusol) intravenously at a dose 250 ml and infusion rate 3 ml/min.
arm group label: Unifusol 250 ml IV, 4.5 ml/min
arm group type: Experimental
description: Twenty-four healthy volunteers will receive arginine sodium succinate 1.4% solution (Unifusol) intravenously at a dose 250 ml and infusion rate 4.5 ml/min
arm group label: Unifusol 500 ml IV, 4.5 ml/min
arm group type: Experimental
description: Twelve healthy volunteers will receive arginine sodium succinate 1.4% solution (Unifusol) intravenously at a dose 500 ml and infusion rate 4.5 ml/min
intervention type: Drug
intervention name: arginine sodium succinate
description: Healthy volunteers will receive the experimental drug (arginine sodium succinate 1.4% solution; Unifusol) intravenously at 3 different combinations of dose and infusion rate under the close monitoring of vital signs and other safety parameters.
arm group label: Unifusol 250 ml IV, 3 ml/mil
arm group label: Unifusol 250 ml IV, 4.5 ml/min
arm group label: Unifusol 500 ml IV, 4.5 ml/min
other name: Unifusol
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Vasily B Vasilyuk, MD, PhD
role: Principal Investigator
affiliation: Research Center for Eco-safety
facility: 
facility: 
country: Russian Federation
responsible party type: Sponsor
mesh term: Vascular Diseases
mesh term: Peripheral Vascular Diseases
mesh term: Peripheral Arterial Disease
sharing ipd: No