<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/NCT04428593</url>
  </required_header>
  <id_info>
    <org_study_id>METS-TRE-01</org_study_id>
    <nct_id>NCT04428593</nct_id>
  </id_info>
  <brief_title>Study to Assess Safety, Tolerability and Pharmacokinetics of Treamid in Healthy Volunteers</brief_title>
  <official_title>Double Blind, Randomized, Placebo-controlled Study of Safety and Tolerability of Treamid in Rising Doses at Single and Then Multiple Oral Administration in Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>PHARMENTERPRISES LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>PHARMENTERPRISES LLC</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>
      A double-blind, randomized, placebo-controlled, Phase I clinical study of the safety and&#xD;
      tolerability of increasing doses of Treamid after single and repeated oral administration in&#xD;
      healthy volunteers. The volunteers received the study drug once, and then continued daily&#xD;
      intake for 14 days after a 6-day break. The primary objective of the study was to evaluate&#xD;
      the safety and tolerability profile of Treamid after single and multiple administration based&#xD;
      on the frequency and severity of adverse events and changes in vital signs, laboratory&#xD;
      results, electrocardiography and results of the physical examination. The secondary objective&#xD;
      of the study was to assess pharmacokinetics of active pharmaceutical substance of Treamid.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1 Russian center was approved for participation in this study and was initiated. Healthy&#xD;
      volunteers were enrolled in 1 center. The study consisted of 4 periods: screening, single&#xD;
      administration, multiple administration and follow-up.&#xD;
&#xD;
      All eligible subjects were randomized into the study in appropriate cohort groups&#xD;
      sequentially. Cohort 1 - Treamid or Placebo 5 mg once and then daily 14 days after a 6-day&#xD;
      break; Cohort 2 - Treamid or Placebo 15 mg once and then daily during 14 days after a 6-day&#xD;
      break; Cohort 3 - Treamid or Placebo 50 mg once and then daily during 14 days after a 6-day&#xD;
      break. The decision regarding increasing of the study drug dose for a subsequent cohort was&#xD;
      made by the Data Safety Monitoring Committee on the basis of preliminary safety results&#xD;
      assessment. A total of 16 volunteers received Treamid (4 - 5 mg, 4 -15 mg, 8 - 50 mg) and a&#xD;
      total of 4 volunteers received the placebo during the study participation. The follow-up&#xD;
      period lasted for 4 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 25, 2016</start_date>
  <completion_date type="Actual">November 21, 2016</completion_date>
  <primary_completion_date type="Actual">November 21, 2016</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>Sequential Assignment</intervention_model>
    <intervention_model_description>The dose cohorts were included into the study subsequently based on preliminary safety results evaluation performed by the Data Safety Monitoring Committee. 3 doses of Treamid/placebo (5 mg, 15 mg and 50 mg) were used in the study.The duration of exposure to the study drug was 6 days in each cohort: Day 1, once, at the step of single administration, and then in 6 days, daily, 1 time a day for 14 days at the step of multiple administration.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>Blinding was carried out by using Placebo equivalent to Treamid tablets without active substance and the corresponding labeling of the study drug.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Adverse events per treatment arm Number of Adverse events per treatment arm</measure>
    <time_frame>Day -13 (14 days before first dose) - Day 50</time_frame>
    <description>Adverse events have been classified according to CTCAE ver 4.03. Adverse events will be summarized descriptively by treatment arm. Verbatim terms will be mapped to preferred terms and organ systems using the current Medical Dictionary for Regulatory Activities version. For each preferred term, frequency counts and percentages will be calculated by cohort. The nature, severity, seriousness, and relationship to study drug will be summarized for all study subjects.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of Treamid by assessing AUC0-inf</measure>
    <time_frame>Day 1 and Day 21 (Pre dose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 6, 8 and 12 hours post dose), Day 2 and Day 22 (24 hours post dose), Day 3 (48 hours post dose), Day 4 (72 hours post dose), Days 8 - 12 and Day 15 (Pre dose)</time_frame>
    <description>Area under the curve &quot;concentration of the drug-time&quot; from the time of administration of the drug till infinity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of Treamid by assessing Cmax</measure>
    <time_frame>Day 1 and Day 21 (Pre dose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 6, 8 and 12 hours post dose), Day 2 and Day 22 (24 hours post dose), Day 3 (48 hours post dose), Day 4 (72 hours post dose), Days 8 - 12 and Day 15 (Pre dose)</time_frame>
    <description>Maximum plasma concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of Treamid by assessing AUC0-t</measure>
    <time_frame>Day 1 and Day 21 (Pre dose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 6, 8 and 12 hours post dose), Day 2 and Day 22 (24 hours post dose), Day 3 (48 hours post dose), Day 4 (72 hours post dose), Days 8 - 12 and Day 15 (Pre dose)</time_frame>
    <description>Area under the curve &quot;concentration of the drug-time&quot; from the time of administration of the drug till the time (t) the last blood sampling</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of Treamid by assessing Tmax</measure>
    <time_frame>Day 1 and Day 21 (Pre dose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 6, 8 and 12 hours post dose), Day 2 and Day 22 (24 hours post dose), Day 3 (48 hours post dose), Day 4 (72 hours post dose), Days 8 - 12 and Day 15 (Pre dose)</time_frame>
    <description>Time to maximum drug concentration in the blood plasma administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of Treamid by assessing T1/2</measure>
    <time_frame>Day 1 and Day 21 (Pre dose, 15 minites, 30 minutes, 1, 1.5, 2, 3, 6, 8 and 12 hours post dose), Day 2 and Day 22 (24 hours post dose), Day 3 (48 hours post dose), Day 4 (72 hours post dose), Days 8 - 12 and Day 15 (Pre dose)</time_frame>
    <description>Terminal elimination half-life</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Metabolic Syndrome</condition>
  <arm_group>
    <arm_group_label>Treamid 5 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohort 1 - 5 subjects were randomized in a 4:1 ratio to be treated either Treamid 5 mg (4 subjects) or placebo (1 subject, see placebo arm).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treamid 15 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohort 2 - 5 subjects were randomized in a 4:1 ratio to be treated either Treamid 15 mg (4 subjects) or placebo (1 subject, see placebo arm).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treamid 50 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohort 3 - 5 subjects were randomized in a 8:2 ratio to be treated either Treamid 50 mg (8 subjects) or placebo (2 subjects, see placebo arm).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo comparator arm consists of 4 subjects (1 subject from Сohorts 1 and 2, 2 subjects from Cohort 3).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Treamid 5 mg</intervention_name>
    <description>The volunteers received the study drug once, and then continued daily intake for 14 days after a 6-day break.</description>
    <arm_group_label>Treamid 5 mg</arm_group_label>
    <other_name>XC268BG</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Treamid 15 mg</intervention_name>
    <description>The volunteers received the study drug once, and then continued daily intake for 14 days after a 6-day break.</description>
    <arm_group_label>Treamid 15 mg</arm_group_label>
    <other_name>XC268BG</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Treamid 50 mg</intervention_name>
    <description>The volunteers received the study drug once, and then continued daily intake for 14 days after a 6-day break.</description>
    <arm_group_label>Treamid 50 mg</arm_group_label>
    <other_name>XC268BG</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>The volunteers received the study drug once, and then continued daily intake for 14 days after a 6-day break.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Non-smoking male at the age from 18 to 50 years old (inclusive);&#xD;
&#xD;
          2. Verified diagnosis &quot;healthy&quot; according to standard clinical, laboratory and&#xD;
             instrumental methods of examination;&#xD;
&#xD;
          3. Body mass index from 18.5 to 30 kg/m2 (inclusive);&#xD;
&#xD;
          4. Agreement to use adequate contraception methods during the study and 3 months after&#xD;
             its completion (condoms with spermicide);&#xD;
&#xD;
          5. Signed patient explanation sheet and informed consent for participation in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Chronic diseases of the cardiovascular, bronchopulmonary, neuroendocrine systems and&#xD;
             diseases of the gastrointestinal tract, liver, kidneys, blood;&#xD;
&#xD;
          2. Laboratory deviations from normal values at screening (the deviations will not include&#xD;
             single violations of reference ranges of laboratory parameter if they are not&#xD;
             accompanied with any clinical symptoms, do not require additional examination or&#xD;
             treatment and are not confirmed by values of related laboratory parameters);&#xD;
&#xD;
          3. Regular administration of drugs in less than 2 weeks before starting the study;&#xD;
             administration of drugs effecting on hemodynamics, liver function, and others.&#xD;
             (barbiturates, omeprazole, cimetidine, etc.) in less than 30 days before starting the&#xD;
             study;&#xD;
&#xD;
          4. Antibodies to HIV and hepatitis C, hepatitis B surface antigen, positive test for&#xD;
             syphilis;&#xD;
&#xD;
          5. Unstable sleep architecture (e.g. night work, sleep disorders, insomnia, recently&#xD;
             returned from another time zone, etc.);&#xD;
&#xD;
          6. Signs of alcohol or drug addiction; taking alcohol or narcotic drugs during 4 days&#xD;
             prior to screening (taking more than 10 units of alcohol per week (1 unit of alcohol&#xD;
             is equivalent ½ liters of beer, 200 ml of wine or 50 ml of hard alcoholic beverages);&#xD;
&#xD;
          7. Medical history significant for allergic (including drug intolerance and food&#xD;
             allergies);&#xD;
&#xD;
          8. Symptomatic rhinitis in past medical history during 2 years before screening (allergic&#xD;
             rhinitis, non-allergic rhinitis or allergic coryza);&#xD;
&#xD;
          9. Blood/plasma donation (from 450 ml) in less than 2 months prior to screening;&#xD;
&#xD;
         10. Surgeries in hospital environment (except appendectomy) during 12 weeks prior to&#xD;
             screening;&#xD;
&#xD;
         11. Participation in other clinical studies or taking other investigated drugs during 3&#xD;
             months prior to screening;&#xD;
&#xD;
         12. Inability to understand or comply with the protocol procedures;&#xD;
&#xD;
         13. Acute infectious diseases in less than 4 weeks prior to screening.&#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>Elena A Smolyarchuk, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The First Moscow State Medical University n.a. Sechenov of Ministry of Health of Russian Federation</affiliation>
  </overall_official>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 10, 2020</study_first_submitted>
  <study_first_submitted_qc>June 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>June 15, 2020</last_update_submitted>
  <last_update_submitted_qc>June 15, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 17, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Healthy volunteers</keyword>
  <keyword>PHARMENTERPRISES</keyword>
  <keyword>Phase I</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metabolic Syndrome</mesh_term>
  </condition_browse>
  <!-- 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/NCT04428593
org study id: METS-TRE-01
nct id: NCT04428593
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
A double-blind, randomized, placebo-controlled, Phase I clinical study of the safety and
      tolerability of increasing doses of Treamid after single and repeated oral administration in
      healthy volunteers. The volunteers received the study drug once, and then continued daily
      intake for 14 days after a 6-day break. The primary objective of the study was to evaluate
      the safety and tolerability profile of Treamid after single and multiple administration based
      on the frequency and severity of adverse events and changes in vital signs, laboratory
      results, electrocardiography and results of the physical examination. The secondary objective
      of the study was to assess pharmacokinetics of active pharmaceutical substance of Treamid.
1 Russian center was approved for participation in this study and was initiated. Healthy
      volunteers were enrolled in 1 center. The study consisted of 4 periods: screening, single
      administration, multiple administration and follow-up.

      All eligible subjects were randomized into the study in appropriate cohort groups
      sequentially. Cohort 1 - Treamid or Placebo 5 mg once and then daily 14 days after a 6-day
      break; Cohort 2 - Treamid or Placebo 15 mg once and then daily during 14 days after a 6-day
      break; Cohort 3 - Treamid or Placebo 50 mg once and then daily during 14 days after a 6-day
      break. The decision regarding increasing of the study drug dose for a subsequent cohort was
      made by the Data Safety Monitoring Committee on the basis of preliminary safety results
      assessment. A total of 16 volunteers received Treamid (4 - 5 mg, 4 -15 mg, 8 - 50 mg) and a
      total of 4 volunteers received the placebo during the study participation. The follow-up
      period lasted for 4 weeks.
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: The dose cohorts were included into the study subsequently based on preliminary safety results evaluation performed by the Data Safety Monitoring Committee. 3 doses of Treamid/placebo (5 mg, 15 mg and 50 mg) were used in the study.The duration of exposure to the study drug was 6 days in each cohort: Day 1, once, at the step of single administration, and then in 6 days, daily, 1 time a day for 14 days at the step of multiple administration.
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: Blinding was carried out by using Placebo equivalent to Treamid tablets without active substance and the corresponding labeling of the study drug.
measure: Number of Adverse events per treatment arm Number of Adverse events per treatment arm
time frame: Day -13 (14 days before first dose) - Day 50
description: Adverse events have been classified according to CTCAE ver 4.03. Adverse events will be summarized descriptively by treatment arm. Verbatim terms will be mapped to preferred terms and organ systems using the current Medical Dictionary for Regulatory Activities version. For each preferred term, frequency counts and percentages will be calculated by cohort. The nature, severity, seriousness, and relationship to study drug will be summarized for all study subjects.
measure: Pharmacokinetics of Treamid by assessing AUC0-inf
time frame: Day 1 and Day 21 (Pre dose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 6, 8 and 12 hours post dose), Day 2 and Day 22 (24 hours post dose), Day 3 (48 hours post dose), Day 4 (72 hours post dose), Days 8 - 12 and Day 15 (Pre dose)
description: Area under the curve "concentration of the drug-time" from the time of administration of the drug till infinity
measure: Pharmacokinetics of Treamid by assessing Cmax
time frame: Day 1 and Day 21 (Pre dose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 6, 8 and 12 hours post dose), Day 2 and Day 22 (24 hours post dose), Day 3 (48 hours post dose), Day 4 (72 hours post dose), Days 8 - 12 and Day 15 (Pre dose)
description: Maximum plasma concentration
measure: Pharmacokinetics of Treamid by assessing AUC0-t
time frame: Day 1 and Day 21 (Pre dose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 6, 8 and 12 hours post dose), Day 2 and Day 22 (24 hours post dose), Day 3 (48 hours post dose), Day 4 (72 hours post dose), Days 8 - 12 and Day 15 (Pre dose)
description: Area under the curve "concentration of the drug-time" from the time of administration of the drug till the time (t) the last blood sampling
measure: Pharmacokinetics of Treamid by assessing Tmax
time frame: Day 1 and Day 21 (Pre dose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 6, 8 and 12 hours post dose), Day 2 and Day 22 (24 hours post dose), Day 3 (48 hours post dose), Day 4 (72 hours post dose), Days 8 - 12 and Day 15 (Pre dose)
description: Time to maximum drug concentration in the blood plasma administration
measure: Pharmacokinetics of Treamid by assessing T1/2
time frame: Day 1 and Day 21 (Pre dose, 15 minites, 30 minutes, 1, 1.5, 2, 3, 6, 8 and 12 hours post dose), Day 2 and Day 22 (24 hours post dose), Day 3 (48 hours post dose), Day 4 (72 hours post dose), Days 8 - 12 and Day 15 (Pre dose)
description: Terminal elimination half-life
arm group label: Treamid 5 mg
arm group type: Experimental
description: Cohort 1 - 5 subjects were randomized in a 4:1 ratio to be treated either Treamid 5 mg (4 subjects) or placebo (1 subject, see placebo arm).
arm group label: Treamid 15 mg
arm group type: Experimental
description: Cohort 2 - 5 subjects were randomized in a 4:1 ratio to be treated either Treamid 15 mg (4 subjects) or placebo (1 subject, see placebo arm).
arm group label: Treamid 50 mg
arm group type: Experimental
description: Cohort 3 - 5 subjects were randomized in a 8:2 ratio to be treated either Treamid 50 mg (8 subjects) or placebo (2 subjects, see placebo arm).
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo comparator arm consists of 4 subjects (1 subject from Сohorts 1 and 2, 2 subjects from Cohort 3).
intervention type: Drug
intervention name: Treamid 5 mg
description: The volunteers received the study drug once, and then continued daily intake for 14 days after a 6-day break.
arm group label: Treamid 5 mg
other name: XC268BG
intervention type: Drug
intervention name: Treamid 15 mg
description: The volunteers received the study drug once, and then continued daily intake for 14 days after a 6-day break.
arm group label: Treamid 15 mg
other name: XC268BG
intervention type: Drug
intervention name: Treamid 50 mg
description: The volunteers received the study drug once, and then continued daily intake for 14 days after a 6-day break.
arm group label: Treamid 50 mg
other name: XC268BG
intervention type: Drug
intervention name: Placebo
description: The volunteers received the study drug once, and then continued daily intake for 14 days after a 6-day break.
arm group label: Placebo
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Elena A Smolyarchuk, MD, PhD
role: Principal Investigator
affiliation: The First Moscow State Medical University n.a. Sechenov of Ministry of Health of Russian Federation
responsible party type: Sponsor
mesh term: Metabolic Syndrome