xml: <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/NCT05976100</url>
    </required_header>
    <id_info>
      <org_study_id>NIOCH-01/20</org_study_id>
      <nct_id>NCT05976100</nct_id>
    </id_info>
    <brief_title>Study of the Safety, Tolerability, Pharmacokinetics of NIOCH-14 in Volunteers Aged 18-50 Years</brief_title>
    <official_title>An Open, Simple, Randomized Study of the Safety, Tolerability, Pharmacokinetics of NIOCH-14 in Volunteers Aged 18-50 Years in Parallel Groups</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Federal Budgetary Research Institution State Research Center of Virology and Biotechnology &quot;Vector&quot;</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Federal Budgetary Research Institution State Research Center of Virology and Biotechnology &quot;Vector&quot;</source>
    <oversight_info>
      <has_dmc>No</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>
        The Aim:&#xD;
  &#xD;
        To study safety, tolerability and pharmacokinetics of NIOCH-14 when administered orally using&#xD;
        a set of clinical and laboratory-instrumental methods.&#xD;
  &#xD;
        The research tasks are to:&#xD;
  &#xD;
          -  to assess the safety and tolerability of different single doses of the drug;&#xD;
  &#xD;
          -  to assess the safety and tolerability of different repeated doses of the drug;&#xD;
  &#xD;
          -  to study pharmacokinetics of single and repeated administration of the drug;&#xD;
  &#xD;
          -  to assess the data on safety and tolerability to select the optimal drug dosing schedule&#xD;
             to resolve the issue of conducting phase II clinical trial in an expanded cohort of&#xD;
             volunteers.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        An open, simple, randomized study of the safety, tolerability, and pharmacokinetics of&#xD;
        NIOCH-14 in volunteers aged 18-50 years in parallel groups will be conducted.&#xD;
  &#xD;
        The study included 90 healthy volunteers of both sexes aged 18-50 years who met the inclusion&#xD;
        criteria, had no exclusion criteria and underwent all screening procedures.&#xD;
  &#xD;
        Grouping of the volunteers:&#xD;
  &#xD;
        1) For a single dose of the drug, three groups will be formed: group 1 - 15 volunteers,&#xD;
        single 200-mg oral dose; group 2 - 15 volunteers, single 600-mg oral dose; group 3 - 15&#xD;
        volunteers, single 1200-mg oral dose. Before drug administration, volunteers should be&#xD;
        hospitalized for a day in the hospital of Federal State Budgetary Healthcare Institution&#xD;
        &quot;Medical and Sanitary Unit No. 163 of the Federal Medical and Biological Agency&quot; (FGBUZ&#xD;
        MSCH-163, FMBA Russia).&#xD;
  &#xD;
        The drug will be first given to 5 healthy volunteers in Group 1. The volunteers will be&#xD;
        followed up daily by a clinical investigator for 7 days. In the absence of changes in&#xD;
        clinical analyzes and adverse events and the approval of the findings by the IDMC, the&#xD;
        remaining subjects in Group 1 will begin to receive the drug.&#xD;
  &#xD;
        After 7 days of the follow-up, the first 5 volunteers in Group 2 (600 mg) will start&#xD;
        receiving the drug. After 7 days, the remaining 10 volunteers in Group 2 will receive the&#xD;
        drug.&#xD;
  &#xD;
        The first 5 volunteers in Group 3 will start receiving the drug after obtaining the results&#xD;
        for the volunteers in Group 2.&#xD;
  &#xD;
        If the volunteers feel satisfactory, they will be discharged on the 2nd day, and then will&#xD;
        have to visit the clinical site for examination and identification of adverse events daily&#xD;
        for 7 days, after which all volunteers will be given self- monitoring diaries for&#xD;
        self-completion to record all adverse events. The volunteers have to present for examination&#xD;
        and clinical testing on the 10th, 20th, 30th and 90th day after receiving the drug.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Completed</overall_status>
    <start_date type="Actual">September 4, 2020</start_date>
    <completion_date type="Actual">March 9, 2022</completion_date>
    <primary_completion_date type="Actual">February 27, 2021</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Monitoring of erythrocyte level (in clinical (general) blood test).</measure>
      <time_frame>Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.</time_frame>
      <description>On control days, a clinical (general) blood test is performed: erythrocyte level is measured (10^12 pcs/l). Value changes between time points are calculated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of leukocyte level (in clinical (general) blood test).</measure>
      <time_frame>Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.</time_frame>
      <description>On control days, a clinical (general) blood test is performed: leukocyte level is measured (10⁹ pcs/l). Value changes between time points are calculated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of platelet level (in clinical (general) blood test).</measure>
      <time_frame>Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.</time_frame>
      <description>On control days, a clinical (general) blood test is performed: platelet level is measured (10⁹ pcs/l). Value changes between time points are calculated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of hemoglobin level (in clinical (general) blood test).</measure>
      <time_frame>Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.</time_frame>
      <description>On control days, a clinical (general) blood test is performed: hemoglobin level is measured (g/l). Value changes between time points are calculated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of erythrocyte sedimentation rate (ESR) (in clinical (general) blood test).</measure>
      <time_frame>Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.</time_frame>
      <description>On control days, a clinical (general) blood test is performed: ESR is measured (mm/hr). Value changes between time points are calculated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of stab neutrophil level (in clinical (general) blood test).</measure>
      <time_frame>Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.</time_frame>
      <description>On control days, a clinical (general) blood test is performed: stab neutrophil level is measured (%). Value changes between time points are calculated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of segmented neutrophil level (in clinical (general) blood test).</measure>
      <time_frame>Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.</time_frame>
      <description>On control days, a clinical (general) blood test is performed: segmented neutrophil level is measured (%). Value changes between time points are calculated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of eosinophil level (in clinical (general) blood test).</measure>
      <time_frame>Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.</time_frame>
      <description>On control days, a clinical (general) blood test is performed: eosinophil level is measured (%). Value changes between time points are calculated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of basophil level (in clinical (general) blood test).</measure>
      <time_frame>Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.</time_frame>
      <description>On control days, a clinical (general) blood test is performed: basophil level is measured (%). Value changes between time points are calculated.&#xD;
  10. Monitoring of monocyte level (in clinical (general) blood test).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of monocyte level (in clinical (general) blood test).</measure>
      <time_frame>Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.</time_frame>
      <description>On control days, a clinical (general) blood test is performed: monocyte level is measured (%). Value changes between time points are calculated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of lymphocyte level (in clinical (general) blood test).</measure>
      <time_frame>Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.</time_frame>
      <description>On control days, a clinical (general) blood test is performed: lymphocyte level is measured (%). Value changes between time points are calculated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of alanine transaminase activity (in biochemical blood test).</measure>
      <time_frame>Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.</time_frame>
      <description>On control days, a biochemical blood test is performed: the activity of alanine transaminase is measured (U/l). Value changes between time points are calculated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of aspartate aminotransferase activity (in biochemical blood test).</measure>
      <time_frame>Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.</time_frame>
      <description>On control days, a biochemical blood test is performed: the activity of aspartate aminotransferase is measured (U/l). Value changes between time points are calculated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of alkaline phosphatase activity (in biochemical blood test).</measure>
      <time_frame>Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.</time_frame>
      <description>On control days, a biochemical blood test is performed: the activity of alkaline phosphatase is measured (U/l). Value changes between time points are calculated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of total protein level (in biochemical blood test).</measure>
      <time_frame>Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.</time_frame>
      <description>On control days, a biochemical blood test is performed: total protein level is measured (g/l). Value changes between time points are calculated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of total bilirubin level (in biochemical blood test).</measure>
      <time_frame>Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.</time_frame>
      <description>On control days, a biochemical blood test is performed: total bilirubin level is measured (μmol/l). Value changes between time points are calculated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of glucose level (in biochemical blood test).</measure>
      <time_frame>Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.</time_frame>
      <description>On control days, a biochemical blood test is performed: glucose level is measured (μmol/l). Value changes between time points are calculated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of creatinine level (in biochemical blood test).</measure>
      <time_frame>Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.</time_frame>
      <description>On control days, a biochemical blood test is performed: creatinine level is measured (μmol/l). Value changes between time points are calculated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of urea level (in biochemical blood test).</measure>
      <time_frame>Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.</time_frame>
      <description>On control days, a biochemical blood test is performed: urea level is measured (μmol/l). Value changes between time points are calculated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of thymol test values (in biochemical blood test).</measure>
      <time_frame>Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.</time_frame>
      <description>On control days, a biochemical blood test is performed: thymol test value is measured (S-H). Value changes between time points are calculated</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of C-reactive protein (CRP) level (in biochemical blood test).</measure>
      <time_frame>Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.</time_frame>
      <description>On control days, a biochemical blood test is performed: CRP level is measured (mg/ml). Value changes between time points are calculated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of prothrombin index (PTI) (in biochemical blood test).</measure>
      <time_frame>Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.</time_frame>
      <description>On control days, a biochemical blood test is performed: PTI is measured (%). Value changes between time points are calculated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of urine color (in common urine analysis).</measure>
      <time_frame>Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.</time_frame>
      <description>On control days, a common urine analysis is performed: urine color is assessed. Urine color changes between time points are evaluated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of urine transparency (in common urine analysis).</measure>
      <time_frame>Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.</time_frame>
      <description>On control days, a common urine analysis is performed: urine transparency is assessed.&#xD;
  Urine transparency changes between time points are evaluated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of urine pH (in common urine analysis).</measure>
      <time_frame>Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.</time_frame>
      <description>On control days, a common urine analysis is performed: urine pH is measured. Urine pH changes between time points are calculated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of urine specific density (in common urine analysis).</measure>
      <time_frame>Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.</time_frame>
      <description>On control days, a common urine analysis is performed: urine specific density is measured.&#xD;
  Urine specific density changes between time points are calculated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of protein level (in common urine analysis).</measure>
      <time_frame>Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.</time_frame>
      <description>On control days, a common urine analysis is performed: protein level (g/l) is measured.&#xD;
  Value changes between time points are calculated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of glucose level (in common urine analysis).</measure>
      <time_frame>Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.</time_frame>
      <description>On control days, a common urine analysis is performed: glucose level (μmol/l) is measured.&#xD;
  Value changes between time points are calculated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of leukocyte level (in common urine analysis).</measure>
      <time_frame>Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.</time_frame>
      <description>On control days, a common urine analysis is performed: leukocyte level (10⁹/l) is measured.&#xD;
  Value changes between time points are calculated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of erythrocyte level (in common urine analysis).</measure>
      <time_frame>Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.</time_frame>
      <description>On control days, a common urine analysis is performed: erythrocyte level (10^12 /l) is measured. Value changes between time points are calculated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of bacteria (in common urine analysis).</measure>
      <time_frame>Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.</time_frame>
      <description>On control days, a common urine analysis is performed: bacterial number (units per field) is measured.&#xD;
  Value changes between time points are calculated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring for the occurrence of adverse events and serious adverse events at least likely related to the studied drug during the study.</measure>
      <time_frame>Groups 1-6: at days 2-10, 20, 30, 90.</time_frame>
      <description>At each visit, the occurrence of adverse events and serious adverse events, at least likely related to the studied drug, is monitored. The change in the volunteer's state between time points is evaluated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring for the occurrence of any adverse events during the study.</measure>
      <time_frame>Groups 1-6: at days 2-10, 20, 30, 90.</time_frame>
      <description>At each visit, the incidence of any adverse events is measured. The change in the volunteer's state between time points is evaluated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring for the occurrence of any serious adverse events during the study.</measure>
      <time_frame>Groups 1-6: at days 2-10, 20, 30, 90.</time_frame>
      <description>At each visit, the incidence of any serious adverse events that lead to the exclusion of participant from the study is measured. The change in the volunteer's state between time points is evaluated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of body temperature at regular intervals.</measure>
      <time_frame>Groups 1-6: at days 0, 1-10, 20, 30, 90.</time_frame>
      <description>Body temperature is recorded (degrees Celsius, °C) on control days. Changes in the values of this parameter between time points are calculated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of blood pressure at regular intervals.</measure>
      <time_frame>Groups 1-6: at days 0, 1-10, 20, 30, 90.</time_frame>
      <description>Systolic and diastolic blood pressure is recorded (mm Hg). Changes in the values of this parameter between time points are calculated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of heart rate at specified intervals.</measure>
      <time_frame>Groups 1-6: at days 0, 1-10, 20, 30, 90.</time_frame>
      <description>Heart rate is recorded (beats per minute) on control days. Changes in the values of this parameter between time points are calculated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monitoring of respiratory movement frequency at specified intervals.</measure>
      <time_frame>Groups 1-6: at days 0, 1-10, 20, 30, 90.</time_frame>
      <description>On the control days, the frequency of respiratory movements (per minute) is recorded. Changes in the values of this parameter between time points are calculated.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Electrocardiography findings (ECG).</measure>
      <time_frame>Groups 1-6: at days 0, 1, 3, 7.</time_frame>
      <description>On control days, a planned standard 12-lead ECG is performed (with measurement of heart rate [HR], PR, QRS, QT intervals and QTc calculation). It is performed in the supine position after 5 minutes of rest. The rhythm record in the respective leads must contain measurable data for at least three cardiac cycles. Changes in the values between time points are calculated.&#xD;
  If there are any changes in the ECG, the clinical investigator should evaluate their clinical significance.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Abdominal ultrasound findings.</measure>
      <time_frame>Groups 1-6: at days 0, 7.</time_frame>
      <description>On control days, the absence of signs of abdominal organ changes is monitored using ultrasound.&#xD;
  Changes in the values between time points are calculated.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Monitoring of the pharmacokinetic parameter &quot;Cmax&quot; for ST-246 (active metabolite of NIOCH-14)</measure>
      <time_frame>Groups 1-3: at days 1-5; groups 4-6: at days 1-10.</time_frame>
      <description>On control days, blood concentration of the active NIOCH-14 metabolite, namely ST-246, is determined using mass spectrometry. The maximum concentration of a substance in the blood plasma, achieved after substance absorption (pharmacokinetic parameter Cmax) is measured. Changes in the values of this parameter between time points are calculated.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Monitoring of the pharmacokinetic parameter &quot;Tmax&quot; for ST-246 (active metabolite of NIOCH-14)</measure>
      <time_frame>Groups 1-3: at days 1-5; groups 4-6: at days 1-10.</time_frame>
      <description>On control days, blood concentration of the active NIOCH-14 metabolite, namely ST-246, is determined using mass spectrometry. The pharmacokinetic parameter Tmax (the time point when the maximum concentration of a substance in the blood is reached) is measured. Changes in the values of this parameter between time points are calculated.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Monitoring of the pharmacokinetic parameter &quot;Cmax /AUC&quot; for ST-246 (active metabolite of NIOCH-14)</measure>
      <time_frame>Groups 1-3: at days 1-5; groups 4-6: at days 1-10.</time_frame>
      <description>On control days, blood concentration of the active NIOCH-14 metabolite, namely ST-246, is determined using mass spectrometry. The pharmacokinetic parameter &quot;Cmax /AUC&quot; (the rate of substance entry into the systemic circulation from the injection site) is measured. Changes in the values of this parameter between time points are calculated.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Monitoring of the pharmacokinetic parameter &quot;Elimination rate&quot; for ST-246 (active metabolite of NIOCH-14)</measure>
      <time_frame>Groups 1-3: at days 1-5; groups 4-6: at days 1-10.</time_frame>
      <description>On control days, blood concentration of the active NIOCH-14 metabolite, namely ST-246, is determined using mass spectrometry. The pharmacokinetic parameter &quot;Elimination rate&quot; (the rate of substance elimination from systemic circulation through biotransformation (metabolism) in the body, and excretion) is measured. Changes in the values of this parameter between time points are calculated.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Monitoring of the pharmacokinetic parameter &quot;T½&quot; for ST-246 (active metabolite of NIOCH-14)</measure>
      <time_frame>Groups 1-3: at days 1-5; groups 4-6: at days 1-10.</time_frame>
      <description>On control days, blood concentration of the active NIOCH-14 metabolite, namely ST-246, is determined using mass spectrometry. The pharmacokinetic parameter &quot;T½&quot; (half-life, the time of 50% substance concentration reduction in plasma) is measured. Changes in the values of this parameter between time points are calculated.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Monitoring of the pharmacokinetic parameter &quot;AUC&quot; for ST-246 (active metabolite of NIOCH-14)</measure>
      <time_frame>Groups 1-3: at days 1-5; groups 4-6: at days 1-10.</time_frame>
      <description>On control days, blood concentration of the active NIOCH-14 metabolite, namely ST-246, is determined using mass spectrometry. The pharmacokinetic parameter &quot;AUC&quot; (area under the curve. It is the integral parameter that characterizes the total amount of a substance entering the blood) is measured. Changes in the values of this parameter between time points are calculated.</description>
    </secondary_outcome>
    <number_of_arms>6</number_of_arms>
    <enrollment type="Actual">90</enrollment>
    <condition>Smallpox</condition>
    <condition>Monkeypox</condition>
    <condition>Cowpox</condition>
    <condition>Vaccinia Virus Infection</condition>
    <arm_group>
      <arm_group_label>Group 1 (15 volunteers)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Single use:&#xD;
  Single 200-mg oral dose of NIOCH-14</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Group 2 (15 volunteers)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Single use:&#xD;
  Single 600-mg oral dose of NIOCH-14</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Group 3 (15 volunteers)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Single use:&#xD;
  Single 1200-mg oral dose of NIOCH-14 (on the same day in the morning 600 mg and in the evening 600 mg)</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Group 4 (15 volunteers)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Multiple application:&#xD;
  Daily 200-mg oral dose of NIOCH-14 once a day for 6 days</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Group 5 (15 volunteers)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Multiple application:&#xD;
  Daily 600-mg oral dose of NIOCH-14 once a day for 6 days</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Group 6 (15 volunteers)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Multiple application:&#xD;
  Daily 600-mg oral dose of NIOCH-14 twice a day for 6 days</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>NIOCH-14, 200 mg capsule: 1 capsule (200 mg) of NIOCH-14 once orally</intervention_name>
      <description>Volunteers take 1 capsule (200 mg) of NIOCH-14 as a single oral dose.</description>
      <arm_group_label>Group 1 (15 volunteers)</arm_group_label>
      <other_name>7-[N-(4-trifluoromethylbenzoyl)-hydrazinocarbonyl]-tricyclo-[3.2.2.02,4]non-8-en-6-carboxylic acid, 200 mg capsule</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>NIOCH-14, 200 mg capsule: 3 capsules (200 mg each) of NIOCH-14 once orally. (Total 600 mg NIOCH-14 per day)</intervention_name>
      <description>Volunteers take 3 capsules (200 mg each) of NIOCH-14 as a single oral dose. (Total 600 mg NIOCH-14 per day)</description>
      <arm_group_label>Group 2 (15 volunteers)</arm_group_label>
      <other_name>7-[N-(4-trifluoromethylbenzoyl)-hydrazinocarbonyl]-tricyclo-[3.2.2.02,4]non-8-en-6-carboxylic acid, 200 mg capsule</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>NIOCH-14, 200 mg capsule: 6 capsules (200 mg each) of NIOCH-14 per day orally. (Total 1200 mg NIOCH-14 per day)</intervention_name>
      <description>Single 1200-mg oral dose. (1200-mg dose of the drug is administered by 600 mg twice a day at 8-00 and 20-00 in the hospital and presence of a clinical investigator or a nurse).</description>
      <arm_group_label>Group 3 (15 volunteers)</arm_group_label>
      <other_name>7-[N-(4-trifluoromethylbenzoyl)-hydrazinocarbonyl]-tricyclo-[3.2.2.02,4]non-8-en-6-carboxylic acid, 200 mg capsule</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>NIOCH-14, 200 mg capsule: 1 capsule (200 mg) of NIOCH-14 a day orally for 6 days</intervention_name>
      <description>Volunteers take 1 capsule (200 mg) of NIOCH-14 a day orally for 6 days.</description>
      <arm_group_label>Group 4 (15 volunteers)</arm_group_label>
      <other_name>7-[N-(4-trifluoromethylbenzoyl)-hydrazinocarbonyl]-tricyclo-[3.2.2.02,4]non-8-en-6-carboxylic acid, 200 mg capsule</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>NIOCH-14, 200 mg capsule: 3 capsules (200 mg each) of NIOCH-14 a day orally for 6 days. (Total 600 mg NIOCH-14 per day for 6 days)</intervention_name>
      <description>Volunteers take 3 capsules (200 mg each) of NIOCH-14 a day orally for 6 days.</description>
      <arm_group_label>Group 5 (15 volunteers)</arm_group_label>
      <other_name>7-[N-(4-trifluoromethylbenzoyl)-hydrazinocarbonyl]-tricyclo-[3.2.2.02,4]non-8-en-6-carboxylic acid, 200 mg capsule</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>NIOCH-14, 200 mg capsule: 3 capsules (200 mg each) of NIOCH-14 twice a day orally for 6 days. (Total 1200 mg NIOCH-14 per day for 6 days)</intervention_name>
      <description>Volunteers take 3 capsules (200 mg each) of NIOCH-14 twice a day orally for 6 days.</description>
      <arm_group_label>Group 6 (15 volunteers)</arm_group_label>
      <other_name>7-[N-(4-trifluoromethylbenzoyl)-hydrazinocarbonyl]-tricyclo-[3.2.2.02,4]non-8-en-6-carboxylic acid, 200 mg capsule</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Signed and dated informed consent of a volunteer to participate in the clinical study,&#xD;
               obtained prior to any of the study procedures.&#xD;
  &#xD;
            2. A verified diagnosis &quot;healthy&quot; based on findings of standard clinical, laboratory and&#xD;
               instrumental methods of examination.&#xD;
  &#xD;
            3. Age from 18 to 50 years inclusive.&#xD;
  &#xD;
            4. Body mass index from 18.5 to 30 kg/m3.&#xD;
  &#xD;
            5. Ability to attend all scheduled visits and all scheduled procedures and examinations.&#xD;
  &#xD;
            6. Consent of volunteers to use effective methods of contraception throughout the study.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Known hypersensitivity to any component of the studied drug.&#xD;
  &#xD;
            2. Aggravated history of allergies.&#xD;
  &#xD;
            3. Drug intolerance.&#xD;
  &#xD;
            4. Pregnancy and the period of breastfeeding.&#xD;
  &#xD;
            5. Military personnel.&#xD;
  &#xD;
            6. Persons in custody in pre-trial detention centers and serving sentences in&#xD;
               penitentiaries.&#xD;
  &#xD;
            7. Children's age under 18.&#xD;
  &#xD;
            8. Acute infectious diseases less than 4 weeks before the start of the study.&#xD;
  &#xD;
            9. Acute or chronic diseases of the cardiovascular, bronchopulmonary, neuroendocrine&#xD;
               system, as well as diseases of the gastrointestinal tract, liver, blood, kidneys,&#xD;
               surgical interventions to the gastrointestinal tract (with the exception of&#xD;
               appendectomy).&#xD;
  &#xD;
           10. Immunosuppressive conditions: congenital or acquired immunodeficiency syndrome&#xD;
               (including HIV infection), leukemia, malignant tumors, organ transplantation, cellular&#xD;
               and humoral immunodeficiencies.&#xD;
  &#xD;
           11. Immunosuppressive therapy: treatment with antimetabolites, high doses of&#xD;
               corticosteroids for 14 days or more, radio and x-ray therapy, etc.&#xD;
  &#xD;
           12. Regular medication intake less than 2 weeks prior to the start of the study.&#xD;
  &#xD;
           13. Taking medications that have a pronounced effect on hemodynamics, liver function, etc.&#xD;
               (barbiturates, omeprazole, cimetidine, etc.) less than 30 days before the start of the&#xD;
               study.&#xD;
  &#xD;
           14. Donation (450 ml of blood or plasma or more) less than 2 months before the start of&#xD;
               the study.&#xD;
  &#xD;
           15. Participation in other clinical trials less than 3 months prior to study enrollment.&#xD;
  &#xD;
           16. Drinking more than 10 units of alcohol per week (1 unit of alcohol is equivalent to ½&#xD;
               liter of beer, 200 ml of wine or 50 ml of alcohol) or a history of alcoholism, drug&#xD;
               addiction, drug abuse.&#xD;
  &#xD;
           17. Smoking of more than 10 cigarettes a day.&#xD;
  &#xD;
           18. Failure to meet inclusion criteria.&#xD;
  &#xD;
           19. Premenopausal women (last menstrual period ≤ 1 year prior to signing of informed&#xD;
               consent) who are not surgically sterile.&#xD;
  &#xD;
           20. Women with a childbearing potential not using or planning to use acceptable means of&#xD;
               contraception during the study and give no consent to urine pregnancy testing during&#xD;
               the study. Acceptable means of contraception include ectopic devices, oral, implanted,&#xD;
               or injectable contraceptives.&#xD;
  &#xD;
           21. Nervous and mental diseases: central nervous system (CNS) traumas with residual&#xD;
               effects, encephalitis and encephalomyelitis (including post-vaccination), meningitis,&#xD;
               polyradiculoneuritis (including a history of polyradiculoneuritis), epilepsy,&#xD;
               hydrocephalus in the stage of decompensation or subcompensation, demyelinating and&#xD;
               degenerative nervous system damage (muscle degeneration, etc.), stroke; compensated&#xD;
               hydrocephalus, Down's disease, Little's disease, CNS damage without residual effects,&#xD;
               history of febrile convulsions, mental illnesses.&#xD;
  &#xD;
          Early (premature) exclusion of subjects from the study (reasons for discontinuation of the&#xD;
          studied drug administration):&#xD;
  &#xD;
          After randomization and the start of the clinical phase, a clinical investigator may&#xD;
          exclude a subject early from the study if:&#xD;
  &#xD;
            -  The decision of the clinical investigator to exclude a volunteer is in the best&#xD;
               interests of the volunteer.&#xD;
  &#xD;
            -  Erroneous inclusion (inclusion and non-inclusion criteria were not allowed for) or the&#xD;
               appearance of non-inclusion criteria during the study.&#xD;
  &#xD;
            -  Investigator's or Client's decision to exclude a volunteer from the study due to a&#xD;
               clinically significant protocol deviation/violation of the protocol.&#xD;
  &#xD;
            -  Any adverse event requiring the prescription of drugs that are not permitted by the&#xD;
               protocol of the study (exacerbation of chronic diseases of the liver, kidneys,&#xD;
               pancreas, heart; occurrence of infectious (influenza and other acute respiratory viral&#xD;
               infections, tonsillitis, hepatitis, etc.) or oncological diseases during the study.&#xD;
  &#xD;
            -  Volunteer's refusal to continue participation in the study or his indiscipline.&#xD;
  &#xD;
            -  Volunteer's desire to terminate the study early for any reason.&#xD;
  &#xD;
            -  Failure of a volunteer to attend a scheduled visit without notifying the clinical&#xD;
               investigator, and loss of communication with a volunteer.&#xD;
  &#xD;
            -  Positive urine drug test and/or alcohol breath test at visits.&#xD;
  &#xD;
            -  Pregnancy. Identification of reasons for premature termination of the study in&#xD;
               enrolled subjects leads to their exclusion from the study at the stage when these&#xD;
               reasons were identified. In each case of premature termination of the study by a&#xD;
               volunteer/exclusion of a volunteer from the study, the clinical investigator must make&#xD;
               an appropriate entry in the Individual Registration Card (IRC) with the obligatory&#xD;
               indication of the reason for the premature termination or exclusion of a volunteer&#xD;
               from the study, and inform the authorized representative of the Customer.&#xD;
        </textblock>
      </criteria>
      <gender>All</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>Vladimir I. Kuzubov, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>FGBUZ MSCH-163, FMBA Russia</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>Federal State Budgetary Healthcare Institution - Medical and Sanitary Unit No. 163 of the Federal Medical and Biological Agency (FGBUZ MSCH-163, FMBA Russia)</name>
        <address>
          <city>Novosibirsk</city>
          <state>Koltsovo, Novosibirsk Region</state>
          <zip>630559</zip>
          <country>Russian Federation</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Russian Federation</country>
    </location_countries>
    <reference>
      <citation>Campe H, Zimmermann P, Glos K, Bayer M, Bergemann H, Dreweck C, Graf P, Weber BK, Meyer H, Buttner M, Busch U, Sing A. Cowpox virus transmission from pet rats to humans, Germany. Emerg Infect Dis. 2009 May;15(5):777-80. doi: 10.3201/eid1505.090159.</citation>
      <PMID>19402967</PMID>
    </reference>
    <reference>
      <citation>Ladnyi I.D. Eradication of Smallpox and Prevention of Its Recurrence. - Moscow: Meditsina, 1985. - 224 P.</citation>
    </reference>
    <reference>
      <citation>Fenner F., Henderson D.A., Arita I., et al. Smallpox and its eradication. - Geneva: World Health Organization, 1988.</citation>
    </reference>
    <reference>
      <citation>Scientific review of variola virus research, 1999-2010//WHO/HSE/GAR/BDP/2010.3. December 2010</citation>
    </reference>
    <reference>
      <citation>Borisevich SV, Marennikova SS, Makhlay AA, Terent'ev AI, Loginova SY, Perekrest VV, Krasnyanskiy VP, Bondarev VP, Rybak SI Cowpox: spread features after the abolition of mandatory smallpox vaccination. Journal of microbiology, epidemiology and immunobiology. 2012; N. 3. 103-107.</citation>
    </reference>
    <reference>
      <citation>Hemmer CJ, Littmann M, Lobermann M, Meyer H, Petschaelis A, Reisinger EC. Human cowpox virus infection acquired from a circus elephant in Germany. Int J Infect Dis. 2010 Sep;14 Suppl 3:e338-40. doi: 10.1016/j.ijid.2010.03.005. Epub 2010 Jun 26.</citation>
      <PMID>20580588</PMID>
    </reference>
    <reference>
      <citation>Ninove L, Domart Y, Vervel C, Voinot C, Salez N, Raoult D, Meyer H, Capek I, Zandotti C, Charrel RN. Cowpox virus transmission from pet rats to humans, France. Emerg Infect Dis. 2009 May;15(5):781-4. doi: 10.3201/eid1505.090235.</citation>
      <PMID>19402968</PMID>
    </reference>
    <reference>
      <citation>Baran V.M., Zubritsky P.K. Human cowpox. Healthcare (Minsk). 1997; No. 3. P. 40</citation>
    </reference>
    <reference>
      <citation>Marennikova SS, Gashnikov PV, Zhukova OA, Riabchikova EI, Strel'tsov VV, Riazankina OI, Chekunova EV, Ianova NN, Shchelkunov SN. [The biotype and genetic characteristics of an isolate of the cowpox virus causing infection in a child]. Zh Mikrobiol Epidemiol Immunobiol. 1996 Jul-Aug;(4):6-10. Russian.</citation>
      <PMID>9027179</PMID>
    </reference>
    <reference>
      <citation>Shchelkunov SN. Emergence and reemergence of smallpox: the need for development of a new generation smallpox vaccine. Vaccine. 2011 Dec 30;29 Suppl 4:D49-53. doi: 10.1016/j.vaccine.2011.05.037. Epub 2011 Dec 18.</citation>
      <PMID>22185833</PMID>
    </reference>
    <reference>
      <citation>Shchelkunov SN. An increasing danger of zoonotic orthopoxvirus infections. PLoS Pathog. 2013;9(12):e1003756. doi: 10.1371/journal.ppat.1003756. Epub 2013 Dec 5.</citation>
      <PMID>24339772</PMID>
    </reference>
    <reference>
      <citation>Marennikova S.S., Shchelkunov S.N. Orthopoxviruses pathogenic to humans. M.: KMK Scientific Press Ltd. - 1998. - 385 P.</citation>
    </reference>
    <reference>
      <citation>Onishchenko G.G., Sandakhchiev L.S., Netesov S.N., Martynyuk R.A. Bioterrorism: national and global threat. - URL: http://www.bio.su/old/press_2006jan_032r.htm.</citation>
    </reference>
    <reference>
      <citation>Yang G, Pevear DC, Davies MH, Collett MS, Bailey T, Rippen S, Barone L, Burns C, Rhodes G, Tohan S, Huggins JW, Baker RO, Buller RL, Touchette E, Waller K, Schriewer J, Neyts J, DeClercq E, Jones K, Hruby D, Jordan R. An orally bioavailable antipoxvirus compound (ST-246) inhibits extracellular virus formation and protects mice from lethal orthopoxvirus Challenge. J Virol. 2005 Oct;79(20):13139-49. doi: 10.1128/JVI.79.20.13139-13149.2005.</citation>
      <PMID>16189015</PMID>
    </reference>
    <reference>
      <citation>Burgasov P.N., Nikolaevsky G.P. Smallpox. - M.: Medicine, 1972. - 207 P.</citation>
    </reference>
    <reference>
      <citation>Mazurkov OY, Kabanov AS, Shishkina LN, Sergeev AA, Skarnovich MO, Bormotov NI, Skarnovich MA, Ovchinnikova AS, Titova KA, Galahova DO, Bulychev LE, Sergeev AA, Taranov OS, Selivanov BA, Tikhonov AY, Zavjalov EL, Agafonov AP, Sergeev AN. New effective chemically synthesized anti-smallpox compound NIOCH-14. J Gen Virol. 2016 May;97(5):1229-1239. doi: 10.1099/jgv.0.000422. Epub 2016 Feb 8.</citation>
      <PMID>26861777</PMID>
    </reference>
    <reference>
      <citation>Mazurkov OY, Shishkina LN, Bormotov NI, Skarnovich MO, Serova OA, Mazurkova NA, Chernonosov AA, Tikhonov AY, Selivanov BA. Estimation of Absolute Bioavailability of the Chemical Substance of the Anti-Smallpox Preparation NIOCH-14 in Mice. Bull Exp Biol Med. 2020 Dec;170(2):207-210. doi: 10.1007/s10517-020-05034-x. Epub 2020 Dec 2.</citation>
      <PMID>33263846</PMID>
    </reference>
    <reference>
      <citation>Selivanov B.A., et al. 7-[N'-(4-trifluoromethylbenzoyl)-hydrazinocarbonyl]-tricyclo[3.2.2.02,4]non-8-ene-6-carboxylic acid, having antiviral activity. Patent RU No. 2412160, publ. 20.02.2011, Bull. No. 5.</citation>
    </reference>
    <reference>
      <citation>Shishkina L.N., Sergeev A.N., Agafonov A.P., Sergeev A.A., Kabanov A.S., Bulychev L.E., Sergeev A.A., Galakhova D.O., Pyankov O.V., Bormotov N.I., Shchukin G.I., Selivanov B.A., Tikhonov A.Ya. Medicated product for smallpox virus and method for producing and using it. Patent RU No. 2543338, publ. 02/27/2015, Bulletin No. 6.</citation>
    </reference>
    <reference>
      <citation>Chen Y, Amantana A, Tyavanagimatt SR, Zima D, Yan XS, Kasi G, Weeks M, Stone MA, Weimers WC, Samuel P, Tan Y, Jones KF, Lee DR, Kickner SS, Saville BM, Lauzon M, McIntyre A, Honeychurch KM, Jordan R, Hruby DE, Leeds JM. Comparison of the safety and pharmacokinetics of ST-246(R) after i.v. infusion or oral administration in mice, rabbits and monkeys. PLoS One. 2011;6(8):e23237. doi: 10.1371/journal.pone.0023237. Epub 2011 Aug 15.</citation>
      <PMID>21858040</PMID>
    </reference>
    <reference>
      <citation>van Gerven J, Bonelli M. Commentary on the EMA Guideline on strategies to identify and mitigate risks for first-in-human and early clinical trials with investigational medicinal products. Br J Clin Pharmacol. 2018 Jul;84(7):1401-1409. doi: 10.1111/bcp.13550. Epub 2018 May 30. No abstract available.</citation>
      <PMID>29451320</PMID>
    </reference>
    <verification_date>March 2023</verification_date>
    <study_first_submitted>June 27, 2023</study_first_submitted>
    <study_first_submitted_qc>July 27, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 4, 2023</study_first_posted>
    <last_update_submitted>July 27, 2023</last_update_submitted>
    <last_update_submitted_qc>July 27, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 4, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Оrthopoxviruses</keyword>
    <keyword>Smallpox</keyword>
    <keyword>NIOCH-14</keyword>
    <keyword>Сlinical study</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Vaccinia</mesh_term>
      <mesh_term>Smallpox</mesh_term>
      <mesh_term>Monkeypox</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05976100
  org study id: NIOCH-01/20
  nct id: NCT05976100
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The Aim:
  
        To study safety, tolerability and pharmacokinetics of NIOCH-14 when administered orally using
        a set of clinical and laboratory-instrumental methods.
  
        The research tasks are to:
  
          -  to assess the safety and tolerability of different single doses of the drug;
  
          -  to assess the safety and tolerability of different repeated doses of the drug;
  
          -  to study pharmacokinetics of single and repeated administration of the drug;
  
          -  to assess the data on safety and tolerability to select the optimal drug dosing schedule
             to resolve the issue of conducting phase II clinical trial in an expanded cohort of
             volunteers.
  An open, simple, randomized study of the safety, tolerability, and pharmacokinetics of
        NIOCH-14 in volunteers aged 18-50 years in parallel groups will be conducted.
  
        The study included 90 healthy volunteers of both sexes aged 18-50 years who met the inclusion
        criteria, had no exclusion criteria and underwent all screening procedures.
  
        Grouping of the volunteers:
  
        1) For a single dose of the drug, three groups will be formed: group 1 - 15 volunteers,
        single 200-mg oral dose; group 2 - 15 volunteers, single 600-mg oral dose; group 3 - 15
        volunteers, single 1200-mg oral dose. Before drug administration, volunteers should be
        hospitalized for a day in the hospital of Federal State Budgetary Healthcare Institution
        "Medical and Sanitary Unit No. 163 of the Federal Medical and Biological Agency" (FGBUZ
        MSCH-163, FMBA Russia).
  
        The drug will be first given to 5 healthy volunteers in Group 1. The volunteers will be
        followed up daily by a clinical investigator for 7 days. In the absence of changes in
        clinical analyzes and adverse events and the approval of the findings by the IDMC, the
        remaining subjects in Group 1 will begin to receive the drug.
  
        After 7 days of the follow-up, the first 5 volunteers in Group 2 (600 mg) will start
        receiving the drug. After 7 days, the remaining 10 volunteers in Group 2 will receive the
        drug.
  
        The first 5 volunteers in Group 3 will start receiving the drug after obtaining the results
        for the volunteers in Group 2.
  
        If the volunteers feel satisfactory, they will be discharged on the 2nd day, and then will
        have to visit the clinical site for examination and identification of adverse events daily
        for 7 days, after which all volunteers will be given self- monitoring diaries for
        self-completion to record all adverse events. The volunteers have to present for examination
        and clinical testing on the 10th, 20th, 30th and 90th day after receiving the drug.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Monitoring of erythrocyte level (in clinical (general) blood test).
  time frame: Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.
  description: On control days, a clinical (general) blood test is performed: erythrocyte level is measured (10^12 pcs/l). Value changes between time points are calculated.
  measure: Monitoring of leukocyte level (in clinical (general) blood test).
  time frame: Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.
  description: On control days, a clinical (general) blood test is performed: leukocyte level is measured (10⁹ pcs/l). Value changes between time points are calculated.
  measure: Monitoring of platelet level (in clinical (general) blood test).
  time frame: Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.
  description: On control days, a clinical (general) blood test is performed: platelet level is measured (10⁹ pcs/l). Value changes between time points are calculated.
  measure: Monitoring of hemoglobin level (in clinical (general) blood test).
  time frame: Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.
  description: On control days, a clinical (general) blood test is performed: hemoglobin level is measured (g/l). Value changes between time points are calculated.
  measure: Monitoring of erythrocyte sedimentation rate (ESR) (in clinical (general) blood test).
  time frame: Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.
  description: On control days, a clinical (general) blood test is performed: ESR is measured (mm/hr). Value changes between time points are calculated.
  measure: Monitoring of stab neutrophil level (in clinical (general) blood test).
  time frame: Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.
  description: On control days, a clinical (general) blood test is performed: stab neutrophil level is measured (%). Value changes between time points are calculated.
  measure: Monitoring of segmented neutrophil level (in clinical (general) blood test).
  time frame: Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.
  description: On control days, a clinical (general) blood test is performed: segmented neutrophil level is measured (%). Value changes between time points are calculated.
  measure: Monitoring of eosinophil level (in clinical (general) blood test).
  time frame: Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.
  description: On control days, a clinical (general) blood test is performed: eosinophil level is measured (%). Value changes between time points are calculated.
  measure: Monitoring of basophil level (in clinical (general) blood test).
  time frame: Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.
  description: On control days, a clinical (general) blood test is performed: basophil level is measured (%). Value changes between time points are calculated.
  10. Monitoring of monocyte level (in clinical (general) blood test).
  measure: Monitoring of monocyte level (in clinical (general) blood test).
  time frame: Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.
  description: On control days, a clinical (general) blood test is performed: monocyte level is measured (%). Value changes between time points are calculated.
  measure: Monitoring of lymphocyte level (in clinical (general) blood test).
  time frame: Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.
  description: On control days, a clinical (general) blood test is performed: lymphocyte level is measured (%). Value changes between time points are calculated.
  measure: Monitoring of alanine transaminase activity (in biochemical blood test).
  time frame: Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.
  description: On control days, a biochemical blood test is performed: the activity of alanine transaminase is measured (U/l). Value changes between time points are calculated.
  measure: Monitoring of aspartate aminotransferase activity (in biochemical blood test).
  time frame: Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.
  description: On control days, a biochemical blood test is performed: the activity of aspartate aminotransferase is measured (U/l). Value changes between time points are calculated.
  measure: Monitoring of alkaline phosphatase activity (in biochemical blood test).
  time frame: Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.
  description: On control days, a biochemical blood test is performed: the activity of alkaline phosphatase is measured (U/l). Value changes between time points are calculated.
  measure: Monitoring of total protein level (in biochemical blood test).
  time frame: Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.
  description: On control days, a biochemical blood test is performed: total protein level is measured (g/l). Value changes between time points are calculated.
  measure: Monitoring of total bilirubin level (in biochemical blood test).
  time frame: Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.
  description: On control days, a biochemical blood test is performed: total bilirubin level is measured (μmol/l). Value changes between time points are calculated.
  measure: Monitoring of glucose level (in biochemical blood test).
  time frame: Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.
  description: On control days, a biochemical blood test is performed: glucose level is measured (μmol/l). Value changes between time points are calculated.
  measure: Monitoring of creatinine level (in biochemical blood test).
  time frame: Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.
  description: On control days, a biochemical blood test is performed: creatinine level is measured (μmol/l). Value changes between time points are calculated.
  measure: Monitoring of urea level (in biochemical blood test).
  time frame: Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.
  description: On control days, a biochemical blood test is performed: urea level is measured (μmol/l). Value changes between time points are calculated.
  measure: Monitoring of thymol test values (in biochemical blood test).
  time frame: Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.
  description: On control days, a biochemical blood test is performed: thymol test value is measured (S-H). Value changes between time points are calculated
  measure: Monitoring of C-reactive protein (CRP) level (in biochemical blood test).
  time frame: Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.
  description: On control days, a biochemical blood test is performed: CRP level is measured (mg/ml). Value changes between time points are calculated.
  measure: Monitoring of prothrombin index (PTI) (in biochemical blood test).
  time frame: Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.
  description: On control days, a biochemical blood test is performed: PTI is measured (%). Value changes between time points are calculated.
  measure: Monitoring of urine color (in common urine analysis).
  time frame: Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.
  description: On control days, a common urine analysis is performed: urine color is assessed. Urine color changes between time points are evaluated.
  measure: Monitoring of urine transparency (in common urine analysis).
  time frame: Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.
  description: On control days, a common urine analysis is performed: urine transparency is assessed.
  Urine transparency changes between time points are evaluated.
  measure: Monitoring of urine pH (in common urine analysis).
  time frame: Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.
  description: On control days, a common urine analysis is performed: urine pH is measured. Urine pH changes between time points are calculated.
  measure: Monitoring of urine specific density (in common urine analysis).
  time frame: Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.
  description: On control days, a common urine analysis is performed: urine specific density is measured.
  Urine specific density changes between time points are calculated.
  measure: Monitoring of protein level (in common urine analysis).
  time frame: Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.
  description: On control days, a common urine analysis is performed: protein level (g/l) is measured.
  Value changes between time points are calculated.
  measure: Monitoring of glucose level (in common urine analysis).
  time frame: Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.
  description: On control days, a common urine analysis is performed: glucose level (μmol/l) is measured.
  Value changes between time points are calculated.
  measure: Monitoring of leukocyte level (in common urine analysis).
  time frame: Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.
  description: On control days, a common urine analysis is performed: leukocyte level (10⁹/l) is measured.
  Value changes between time points are calculated.
  measure: Monitoring of erythrocyte level (in common urine analysis).
  time frame: Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.
  description: On control days, a common urine analysis is performed: erythrocyte level (10^12 /l) is measured. Value changes between time points are calculated.
  measure: Monitoring of bacteria (in common urine analysis).
  time frame: Groups 1-6: at days 0, 3, 7, 10, 20, 30, 90.
  description: On control days, a common urine analysis is performed: bacterial number (units per field) is measured.
  Value changes between time points are calculated.
  measure: Monitoring for the occurrence of adverse events and serious adverse events at least likely related to the studied drug during the study.
  time frame: Groups 1-6: at days 2-10, 20, 30, 90.
  description: At each visit, the occurrence of adverse events and serious adverse events, at least likely related to the studied drug, is monitored. The change in the volunteer's state between time points is evaluated.
  measure: Monitoring for the occurrence of any adverse events during the study.
  time frame: Groups 1-6: at days 2-10, 20, 30, 90.
  description: At each visit, the incidence of any adverse events is measured. The change in the volunteer's state between time points is evaluated.
  measure: Monitoring for the occurrence of any serious adverse events during the study.
  time frame: Groups 1-6: at days 2-10, 20, 30, 90.
  description: At each visit, the incidence of any serious adverse events that lead to the exclusion of participant from the study is measured. The change in the volunteer's state between time points is evaluated.
  measure: Monitoring of body temperature at regular intervals.
  time frame: Groups 1-6: at days 0, 1-10, 20, 30, 90.
  description: Body temperature is recorded (degrees Celsius, °C) on control days. Changes in the values of this parameter between time points are calculated.
  measure: Monitoring of blood pressure at regular intervals.
  time frame: Groups 1-6: at days 0, 1-10, 20, 30, 90.
  description: Systolic and diastolic blood pressure is recorded (mm Hg). Changes in the values of this parameter between time points are calculated.
  measure: Monitoring of heart rate at specified intervals.
  time frame: Groups 1-6: at days 0, 1-10, 20, 30, 90.
  description: Heart rate is recorded (beats per minute) on control days. Changes in the values of this parameter between time points are calculated.
  measure: Monitoring of respiratory movement frequency at specified intervals.
  time frame: Groups 1-6: at days 0, 1-10, 20, 30, 90.
  description: On the control days, the frequency of respiratory movements (per minute) is recorded. Changes in the values of this parameter between time points are calculated.
  measure: Electrocardiography findings (ECG).
  time frame: Groups 1-6: at days 0, 1, 3, 7.
  description: On control days, a planned standard 12-lead ECG is performed (with measurement of heart rate [HR], PR, QRS, QT intervals and QTc calculation). It is performed in the supine position after 5 minutes of rest. The rhythm record in the respective leads must contain measurable data for at least three cardiac cycles. Changes in the values between time points are calculated.
  If there are any changes in the ECG, the clinical investigator should evaluate their clinical significance.
  measure: Abdominal ultrasound findings.
  time frame: Groups 1-6: at days 0, 7.
  description: On control days, the absence of signs of abdominal organ changes is monitored using ultrasound.
  Changes in the values between time points are calculated.
  measure: Monitoring of the pharmacokinetic parameter "Cmax" for ST-246 (active metabolite of NIOCH-14)
  time frame: Groups 1-3: at days 1-5; groups 4-6: at days 1-10.
  description: On control days, blood concentration of the active NIOCH-14 metabolite, namely ST-246, is determined using mass spectrometry. The maximum concentration of a substance in the blood plasma, achieved after substance absorption (pharmacokinetic parameter Cmax) is measured. Changes in the values of this parameter between time points are calculated.
  measure: Monitoring of the pharmacokinetic parameter "Tmax" for ST-246 (active metabolite of NIOCH-14)
  time frame: Groups 1-3: at days 1-5; groups 4-6: at days 1-10.
  description: On control days, blood concentration of the active NIOCH-14 metabolite, namely ST-246, is determined using mass spectrometry. The pharmacokinetic parameter Tmax (the time point when the maximum concentration of a substance in the blood is reached) is measured. Changes in the values of this parameter between time points are calculated.
  measure: Monitoring of the pharmacokinetic parameter "Cmax /AUC" for ST-246 (active metabolite of NIOCH-14)
  time frame: Groups 1-3: at days 1-5; groups 4-6: at days 1-10.
  description: On control days, blood concentration of the active NIOCH-14 metabolite, namely ST-246, is determined using mass spectrometry. The pharmacokinetic parameter "Cmax /AUC" (the rate of substance entry into the systemic circulation from the injection site) is measured. Changes in the values of this parameter between time points are calculated.
  measure: Monitoring of the pharmacokinetic parameter "Elimination rate" for ST-246 (active metabolite of NIOCH-14)
  time frame: Groups 1-3: at days 1-5; groups 4-6: at days 1-10.
  description: On control days, blood concentration of the active NIOCH-14 metabolite, namely ST-246, is determined using mass spectrometry. The pharmacokinetic parameter "Elimination rate" (the rate of substance elimination from systemic circulation through biotransformation (metabolism) in the body, and excretion) is measured. Changes in the values of this parameter between time points are calculated.
  measure: Monitoring of the pharmacokinetic parameter "T½" for ST-246 (active metabolite of NIOCH-14)
  time frame: Groups 1-3: at days 1-5; groups 4-6: at days 1-10.
  description: On control days, blood concentration of the active NIOCH-14 metabolite, namely ST-246, is determined using mass spectrometry. The pharmacokinetic parameter "T½" (half-life, the time of 50% substance concentration reduction in plasma) is measured. Changes in the values of this parameter between time points are calculated.
  measure: Monitoring of the pharmacokinetic parameter "AUC" for ST-246 (active metabolite of NIOCH-14)
  time frame: Groups 1-3: at days 1-5; groups 4-6: at days 1-10.
  description: On control days, blood concentration of the active NIOCH-14 metabolite, namely ST-246, is determined using mass spectrometry. The pharmacokinetic parameter "AUC" (area under the curve. It is the integral parameter that characterizes the total amount of a substance entering the blood) is measured. Changes in the values of this parameter between time points are calculated.
  arm group label: Group 1 (15 volunteers)
  arm group type: Experimental
  description: Single use:
  Single 200-mg oral dose of NIOCH-14
  arm group label: Group 2 (15 volunteers)
  arm group type: Experimental
  description: Single use:
  Single 600-mg oral dose of NIOCH-14
  arm group label: Group 3 (15 volunteers)
  arm group type: Experimental
  description: Single use:
  Single 1200-mg oral dose of NIOCH-14 (on the same day in the morning 600 mg and in the evening 600 mg)
  arm group label: Group 4 (15 volunteers)
  arm group type: Experimental
  description: Multiple application:
  Daily 200-mg oral dose of NIOCH-14 once a day for 6 days
  arm group label: Group 5 (15 volunteers)
  arm group type: Experimental
  description: Multiple application:
  Daily 600-mg oral dose of NIOCH-14 once a day for 6 days
  arm group label: Group 6 (15 volunteers)
  arm group type: Experimental
  description: Multiple application:
  Daily 600-mg oral dose of NIOCH-14 twice a day for 6 days
  intervention type: Drug
  intervention name: NIOCH-14, 200 mg capsule: 1 capsule (200 mg) of NIOCH-14 once orally
  description: Volunteers take 1 capsule (200 mg) of NIOCH-14 as a single oral dose.
  arm group label: Group 1 (15 volunteers)
  other name: 7-[N-(4-trifluoromethylbenzoyl)-hydrazinocarbonyl]-tricyclo-[3.2.2.02,4]non-8-en-6-carboxylic acid, 200 mg capsule
  intervention type: Drug
  intervention name: NIOCH-14, 200 mg capsule: 3 capsules (200 mg each) of NIOCH-14 once orally. (Total 600 mg NIOCH-14 per day)
  description: Volunteers take 3 capsules (200 mg each) of NIOCH-14 as a single oral dose. (Total 600 mg NIOCH-14 per day)
  arm group label: Group 2 (15 volunteers)
  other name: 7-[N-(4-trifluoromethylbenzoyl)-hydrazinocarbonyl]-tricyclo-[3.2.2.02,4]non-8-en-6-carboxylic acid, 200 mg capsule
  intervention type: Drug
  intervention name: NIOCH-14, 200 mg capsule: 6 capsules (200 mg each) of NIOCH-14 per day orally. (Total 1200 mg NIOCH-14 per day)
  description: Single 1200-mg oral dose. (1200-mg dose of the drug is administered by 600 mg twice a day at 8-00 and 20-00 in the hospital and presence of a clinical investigator or a nurse).
  arm group label: Group 3 (15 volunteers)
  other name: 7-[N-(4-trifluoromethylbenzoyl)-hydrazinocarbonyl]-tricyclo-[3.2.2.02,4]non-8-en-6-carboxylic acid, 200 mg capsule
  intervention type: Drug
  intervention name: NIOCH-14, 200 mg capsule: 1 capsule (200 mg) of NIOCH-14 a day orally for 6 days
  description: Volunteers take 1 capsule (200 mg) of NIOCH-14 a day orally for 6 days.
  arm group label: Group 4 (15 volunteers)
  other name: 7-[N-(4-trifluoromethylbenzoyl)-hydrazinocarbonyl]-tricyclo-[3.2.2.02,4]non-8-en-6-carboxylic acid, 200 mg capsule
  intervention type: Drug
  intervention name: NIOCH-14, 200 mg capsule: 3 capsules (200 mg each) of NIOCH-14 a day orally for 6 days. (Total 600 mg NIOCH-14 per day for 6 days)
  description: Volunteers take 3 capsules (200 mg each) of NIOCH-14 a day orally for 6 days.
  arm group label: Group 5 (15 volunteers)
  other name: 7-[N-(4-trifluoromethylbenzoyl)-hydrazinocarbonyl]-tricyclo-[3.2.2.02,4]non-8-en-6-carboxylic acid, 200 mg capsule
  intervention type: Drug
  intervention name: NIOCH-14, 200 mg capsule: 3 capsules (200 mg each) of NIOCH-14 twice a day orally for 6 days. (Total 1200 mg NIOCH-14 per day for 6 days)
  description: Volunteers take 3 capsules (200 mg each) of NIOCH-14 twice a day orally for 6 days.
  arm group label: Group 6 (15 volunteers)
  other name: 7-[N-(4-trifluoromethylbenzoyl)-hydrazinocarbonyl]-tricyclo-[3.2.2.02,4]non-8-en-6-carboxylic acid, 200 mg capsule
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 50 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Vladimir I. Kuzubov, PhD
  role: Principal Investigator
  affiliation: FGBUZ MSCH-163, FMBA Russia
  facility: 
  country: Russian Federation
  citation: Campe H, Zimmermann P, Glos K, Bayer M, Bergemann H, Dreweck C, Graf P, Weber BK, Meyer H, Buttner M, Busch U, Sing A. Cowpox virus transmission from pet rats to humans, Germany. Emerg Infect Dis. 2009 May;15(5):777-80. doi: 10.3201/eid1505.090159.
  PMID: 19402967
  citation: Ladnyi I.D. Eradication of Smallpox and Prevention of Its Recurrence. - Moscow: Meditsina, 1985. - 224 P.
  citation: Fenner F., Henderson D.A., Arita I., et al. Smallpox and its eradication. - Geneva: World Health Organization, 1988.
  citation: Scientific review of variola virus research, 1999-2010//WHO/HSE/GAR/BDP/2010.3. December 2010
  citation: Borisevich SV, Marennikova SS, Makhlay AA, Terent'ev AI, Loginova SY, Perekrest VV, Krasnyanskiy VP, Bondarev VP, Rybak SI Cowpox: spread features after the abolition of mandatory smallpox vaccination. Journal of microbiology, epidemiology and immunobiology. 2012; N. 3. 103-107.
  citation: Hemmer CJ, Littmann M, Lobermann M, Meyer H, Petschaelis A, Reisinger EC. Human cowpox virus infection acquired from a circus elephant in Germany. Int J Infect Dis. 2010 Sep;14 Suppl 3:e338-40. doi: 10.1016/j.ijid.2010.03.005. Epub 2010 Jun 26.
  PMID: 20580588
  citation: Ninove L, Domart Y, Vervel C, Voinot C, Salez N, Raoult D, Meyer H, Capek I, Zandotti C, Charrel RN. Cowpox virus transmission from pet rats to humans, France. Emerg Infect Dis. 2009 May;15(5):781-4. doi: 10.3201/eid1505.090235.
  PMID: 19402968
  citation: Baran V.M., Zubritsky P.K. Human cowpox. Healthcare (Minsk). 1997; No. 3. P. 40
  citation: Marennikova SS, Gashnikov PV, Zhukova OA, Riabchikova EI, Strel'tsov VV, Riazankina OI, Chekunova EV, Ianova NN, Shchelkunov SN. [The biotype and genetic characteristics of an isolate of the cowpox virus causing infection in a child]. Zh Mikrobiol Epidemiol Immunobiol. 1996 Jul-Aug;(4):6-10. Russian.
  PMID: 9027179
  citation: Shchelkunov SN. Emergence and reemergence of smallpox: the need for development of a new generation smallpox vaccine. Vaccine. 2011 Dec 30;29 Suppl 4:D49-53. doi: 10.1016/j.vaccine.2011.05.037. Epub 2011 Dec 18.
  PMID: 22185833
  citation: Shchelkunov SN. An increasing danger of zoonotic orthopoxvirus infections. PLoS Pathog. 2013;9(12):e1003756. doi: 10.1371/journal.ppat.1003756. Epub 2013 Dec 5.
  PMID: 24339772
  citation: Marennikova S.S., Shchelkunov S.N. Orthopoxviruses pathogenic to humans. M.: KMK Scientific Press Ltd. - 1998. - 385 P.
  citation: Onishchenko G.G., Sandakhchiev L.S., Netesov S.N., Martynyuk R.A. Bioterrorism: national and global threat. - URL: http://www.bio.su/old/press_2006jan_032r.htm.
  citation: Yang G, Pevear DC, Davies MH, Collett MS, Bailey T, Rippen S, Barone L, Burns C, Rhodes G, Tohan S, Huggins JW, Baker RO, Buller RL, Touchette E, Waller K, Schriewer J, Neyts J, DeClercq E, Jones K, Hruby D, Jordan R. An orally bioavailable antipoxvirus compound (ST-246) inhibits extracellular virus formation and protects mice from lethal orthopoxvirus Challenge. J Virol. 2005 Oct;79(20):13139-49. doi: 10.1128/JVI.79.20.13139-13149.2005.
  PMID: 16189015
  citation: Burgasov P.N., Nikolaevsky G.P. Smallpox. - M.: Medicine, 1972. - 207 P.
  citation: Mazurkov OY, Kabanov AS, Shishkina LN, Sergeev AA, Skarnovich MO, Bormotov NI, Skarnovich MA, Ovchinnikova AS, Titova KA, Galahova DO, Bulychev LE, Sergeev AA, Taranov OS, Selivanov BA, Tikhonov AY, Zavjalov EL, Agafonov AP, Sergeev AN. New effective chemically synthesized anti-smallpox compound NIOCH-14. J Gen Virol. 2016 May;97(5):1229-1239. doi: 10.1099/jgv.0.000422. Epub 2016 Feb 8.
  PMID: 26861777
  citation: Mazurkov OY, Shishkina LN, Bormotov NI, Skarnovich MO, Serova OA, Mazurkova NA, Chernonosov AA, Tikhonov AY, Selivanov BA. Estimation of Absolute Bioavailability of the Chemical Substance of the Anti-Smallpox Preparation NIOCH-14 in Mice. Bull Exp Biol Med. 2020 Dec;170(2):207-210. doi: 10.1007/s10517-020-05034-x. Epub 2020 Dec 2.
  PMID: 33263846
  citation: Selivanov B.A., et al. 7-[N'-(4-trifluoromethylbenzoyl)-hydrazinocarbonyl]-tricyclo[3.2.2.02,4]non-8-ene-6-carboxylic acid, having antiviral activity. Patent RU No. 2412160, publ. 20.02.2011, Bull. No. 5.
  citation: Shishkina L.N., Sergeev A.N., Agafonov A.P., Sergeev A.A., Kabanov A.S., Bulychev L.E., Sergeev A.A., Galakhova D.O., Pyankov O.V., Bormotov N.I., Shchukin G.I., Selivanov B.A., Tikhonov A.Ya. Medicated product for smallpox virus and method for producing and using it. Patent RU No. 2543338, publ. 02/27/2015, Bulletin No. 6.
  citation: Chen Y, Amantana A, Tyavanagimatt SR, Zima D, Yan XS, Kasi G, Weeks M, Stone MA, Weimers WC, Samuel P, Tan Y, Jones KF, Lee DR, Kickner SS, Saville BM, Lauzon M, McIntyre A, Honeychurch KM, Jordan R, Hruby DE, Leeds JM. Comparison of the safety and pharmacokinetics of ST-246(R) after i.v. infusion or oral administration in mice, rabbits and monkeys. PLoS One. 2011;6(8):e23237. doi: 10.1371/journal.pone.0023237. Epub 2011 Aug 15.
  PMID: 21858040
  citation: van Gerven J, Bonelli M. Commentary on the EMA Guideline on strategies to identify and mitigate risks for first-in-human and early clinical trials with investigational medicinal products. Br J Clin Pharmacol. 2018 Jul;84(7):1401-1409. doi: 10.1111/bcp.13550. Epub 2018 May 30. No abstract available.
  PMID: 29451320
  responsible party type: Sponsor
  mesh term: Vaccinia
  mesh term: Smallpox
  mesh term: Monkeypox
  sharing ipd: No