<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/NCT03036293</url>
  </required_header>
  <id_info>
    <org_study_id>MMH-TN-001</org_study_id>
    <nct_id>NCT03036293</nct_id>
  </id_info>
  <brief_title>Tenoten® in the Treatment of Somatoform, Stress-related and Other Neurotic Disorders</brief_title>
  <official_title>International Multicenter, Double-blind, Randomized Placebo-controlled Phase IV Clinical Trial of Different Dosing Regimens of Tenoten® in the Treatment of Anxiety in Patients With Somatoform, Stress-related and Other Neurotic Disorders</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Materia Medica Holding</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Materia Medica Holding</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 purposes of this study are:&#xD;
&#xD;
        -  To further examine the efficacy and safety of Tenoten® in the treatment of anxiety in&#xD;
           patients with somatoform, stress-related and other neurotic disorders.&#xD;
&#xD;
        -  To compare the efficacy of two dosing regimens of Tenoten® (4 tablets daily vs.8 tablets&#xD;
           daily, both for 12 weeks) in the treatment of anxiety in patients with somatoform,&#xD;
           stress-related and other neurotic disorders.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Design: an international, a multicenter, double-blind, randomized, parallel group&#xD;
      placebo-controlled trial to evaluate efficacy and safety of study treatment.&#xD;
&#xD;
      The study will enroll outpatient subjects of both genders aged 18-45 years with verified&#xD;
      diagnoses of somatoform, stress-related and other neurotic disorders (F43, F45, F48) and&#xD;
      signs of clinically relevant anxiety according to The Hospital Anxiety and Depression scale&#xD;
      (HADS).&#xD;
&#xD;
      After signing the informed consent form to participate in the clinical study the subject will&#xD;
      be interviewed (complaints, medical history, concomitant therapy) and objective examination&#xD;
      will be performed; the subject will fill HADS scale. The severity of anxiety at screening&#xD;
      should be ≥ 11 according to HADS. If the subject meets inclusion criteria and has no&#xD;
      exclusion criteria he/she will be enrolled into the study. The investigator will determine&#xD;
      the severity of anxiety using НАМ-А scale; the subject will fill EQ-5D-3L questionnaire. At&#xD;
      Visit 1 (Day 1) the subject will be randomized into one of the treatment groups:&#xD;
&#xD;
        -  Group 1: Tenoten® at 2 tablets twice daily (4 tablets/day);&#xD;
&#xD;
        -  Group 2: Placebo at 2 tablets twice daily (4 tablets/day);&#xD;
&#xD;
        -  Group 3: Tenoten® at 2 tablets 4 daily (8 tablets/day).&#xD;
&#xD;
        -  Group 4: Placebo at 2 tablets 4 daily (8 tablets/day). The first dose should be&#xD;
           administered at Visit 1 after the visit procedures are completed. Further administration&#xD;
           of the study product will be made according to the dosing scheme. The subject will&#xD;
           administer the study product and will be followed for 12 weeks during which additional&#xD;
           three visits will be made. At Visit 2 (Week 4), Visit 3 (Week 8) and Visit 4 (Week 12)&#xD;
           the physician will record patients' complaints and physical examination data, fill HAM-A&#xD;
           scale, check the study and concomitant therapy, assess treatment safety and patient&#xD;
           compliance with the study treatment. At the final Visit 4 the subject will fill EQ-5D-3L&#xD;
           questionnaire and the investigator will fill the Clinical Global Impression Scale&#xD;
           Efficacy Index (CGI-EI).&#xD;
&#xD;
      Subjects will be allowed to take symptomatic therapy and medications for their co-morbidities&#xD;
      during the study, except for the medicines listed in &quot;Prohibited therapy&quot;.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 8, 2017</start_date>
  <completion_date type="Actual">September 22, 2018</completion_date>
  <primary_completion_date type="Actual">September 22, 2018</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in the Mean HAM-A Score at 12 Weeks of Treatment: 1. Group 1 (Tenoten®, 4 Tablets a Day); 2. Group 3 (Tenoten®, 8 Tablets a Day).</measure>
    <time_frame>12 weeks</time_frame>
    <description>The Hamilton Anxiety Rating Scale (HAM-A). Personality questionnaire designed to identify constitutive anxiety and situational anxiety. The scale consists of 14 items and measures both psychic anxiety and somatic anxiety. Total score is in range 0-56. Includes the symptoms of anxious mood, phobic, emotional, sleep disorders, depressive mood, somatic symptoms - muscular (pain, convulsions, etc.), sensory (e.g. tinnitus), cardiovascular, respiratory, gastrointestinal, genitourinary, neurovegetative. Major role belongs to behaviour during this interview.&#xD;
Anxiety scoring:&#xD;
≤13 - no anxiety; 14-17 - mild anxiety disorder; 18-24 - moderate anxiety disorder;&#xD;
≥25 - severe anxiety.&#xD;
Higher values represent a worse outcome</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Mean HAM-A Score at 4 Weeks of Treatment: 1.1. Group 1 (Tenoten®, 4 Tablets a Day); 1.2. Group 3 (Tenoten®, 8 Tablets a Day).</measure>
    <time_frame>4 weeks</time_frame>
    <description>The Hamilton Anxiety Rating Scale (HAM-A). Personality questionnaire designed to identify constitutive anxiety and situational anxiety. The scale consists of 14 items and measures both psychic anxiety and somatic anxiety. Total score is in range 0-56. Includes the symptoms of anxious mood, phobic, emotional, sleep disorders, depressive mood, somatic symptoms - muscular (pain, convulsions, etc.), sensory (e.g. tinnitus), cardiovascular, respiratory, gastrointestinal, genitourinary, neurovegetative. Major role belongs to behaviour during this interview.&#xD;
Anxiety scoring:&#xD;
≤13 - no anxiety; 14-17 - mild anxiety disorder; 18-24 - moderate anxiety disorder;&#xD;
≥25 - severe anxiety.&#xD;
Higher values represent a worse outcome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Mean HAM-A Score at 8 Weeks of Treatment: 2.1. Group 1 (Tenoten®, 4 Tablets a Day); 2.2. Group 3 (Tenoten®, 8 Tablets a Day).</measure>
    <time_frame>8 weeks</time_frame>
    <description>The Hamilton Anxiety Rating Scale (HAM-A). Personality questionnaire designed to identify constitutive anxiety and situational anxiety. The scale consists of 14 items and measures both psychic anxiety and somatic anxiety. Total score is in range 0-56. Includes the symptoms of anxious mood, phobic, emotional, sleep disorders, depressive mood, somatic symptoms - muscular (pain, convulsions, etc.), sensory (e.g. tinnitus), cardiovascular, respiratory, gastrointestinal, genitourinary, neurovegetative. Major role belongs to behaviour during this interview.&#xD;
Anxiety scoring:&#xD;
≤13 - no anxiety; 14-17 - mild anxiety disorder; 18-24 - moderate anxiety disorder;&#xD;
≥25 - severe anxiety.&#xD;
Higher values represent a worse outcome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients Had at Least a 50% Improvement in the HAM-A Score: 3.1. Group 1 (Tenoten® 4 Tablets a Day): After 4, 8 and 12 Weeks; 3.2. Group 3 (Tenoten® 8 Tablets a Day): After 4, 8 and 12 Weeks.</measure>
    <time_frame>4,8,12 weeks</time_frame>
    <description>The Hamilton Anxiety Rating Scale (HAM-A). Personality questionnaire designed to identify constitutive anxiety and situational anxiety. The scale consists of 14 items and measures both psychic anxiety and somatic anxiety. Total score is in range 0-56. Includes the symptoms of anxious mood, phobic, emotional, sleep disorders, depressive mood, somatic symptoms - muscular (pain, convulsions, etc.), sensory (e.g. tinnitus), cardiovascular, respiratory, gastrointestinal, genitourinary, neurovegetative. Major role belongs to behaviour during this interview.&#xD;
Anxiety scoring:&#xD;
≤13 - no anxiety; 14-17 - mild anxiety disorder; 18-24 - moderate anxiety disorder;&#xD;
≥25 - severe anxiety.&#xD;
Higher values represent a worse outcome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients With no Anxiety (HAM-A Score &lt;14) in: 4.1. Group 1 (Tenoten®, 4 Tablets a Day); After 4, 8 and 12 Weeks; 4.3. Group 3 (Tenoten®, 4 Tablets a Day); After 4, 8 and 12 Weeks.</measure>
    <time_frame>4,8,12 weeks</time_frame>
    <description>The Hamilton Anxiety Rating Scale (HAM-A). Personality questionnaire designed to identify constitutive anxiety and situational anxiety. The scale consists of 14 items and measures both psychic anxiety and somatic anxiety. Total score is in range 0-56. Includes the symptoms of anxious mood, phobic, emotional, sleep disorders, depressive mood, somatic symptoms - muscular (pain, convulsions, etc.), sensory (e.g. tinnitus), cardiovascular, respiratory, gastrointestinal, genitourinary, neurovegetative. Major role belongs to behaviour during this interview.&#xD;
Anxiety scoring:&#xD;
≤13 - no anxiety; 14-17 - mild anxiety disorder; 18-24 - moderate anxiety disorder;&#xD;
≥25 - severe anxiety.&#xD;
Higher values represent a worse outcome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Total EQ-5D-3L Score at 12 Weeks of Treatment in Patients From: 5.1. Group 1 (Tenoten®, 4 Tablets a Day); 5.2. Group 3 (Tenoten®, 8 Tablets a Day).</measure>
    <time_frame>12 weeks</time_frame>
    <description>European Quality of Life Instrument questionnaire (EQ-5D-3L) is designed for the evaluation of the quality of life.The score ranges between 5-15. Higher values represent a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total CGI Scores in Patients From: 6.1. Group 1 (Tenoten®, 4 Tablets a Day); 6.2. Group 3 (Tenoten®, 8 Tablets a Day).</measure>
    <time_frame>12 weeks</time_frame>
    <description>Clinical Global Impession (CGI) provides a brief assessment of the clinician's view of the patient's global functioning prior to and after initiating a study medication. Total range 0-16. Higher values represent a worse outcome</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">390</enrollment>
  <condition>Anxiety</condition>
  <arm_group>
    <arm_group_label>Tenoten, 2 tablets twice daily (4 tablets/day)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in the mouth until dissolution, without meal.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo, 2 tablets twice daily (4 tablets/day)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in the mouth until dissolution, without meal.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tenoten, 2 tablets 4 times daily (8 tablets/day)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets 4 times daily (8 tablets/days). The tablets should be held in the mouth until dissolution, without meal.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo, 2 tablets 4 times daily (8 tablets/day)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets 4 times daily (8 tablets/days). The tablets should be held in the mouth until dissolution, without meal.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tenoten</intervention_name>
    <description>Tablet for oral use.</description>
    <arm_group_label>Tenoten, 2 tablets 4 times daily (8 tablets/day)</arm_group_label>
    <arm_group_label>Tenoten, 2 tablets twice daily (4 tablets/day)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Tablet for oral use.</description>
    <arm_group_label>Placebo, 2 tablets 4 times daily (8 tablets/day)</arm_group_label>
    <arm_group_label>Placebo, 2 tablets twice daily (4 tablets/day)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients of both sexes aged 18-45 years (inclusive).&#xD;
&#xD;
          2. Patients diagnosed with somatoform, stress-related, and other neurotic disorders (F43,&#xD;
             F45, and F48), in accordance with the ICD-10 criteria.&#xD;
&#xD;
          3. A moderate and severe anxiety (HADS score ≥ 11) documented at screening.&#xD;
&#xD;
          4. Patients providing signed Informed Consent form for participation in the clinical&#xD;
             trial.&#xD;
&#xD;
          5. Patients of reproductive age (of both sexes) using contraceptives and contraceptive&#xD;
             methods during the study and for 30 days after the end of participation in the trial.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Moderate and severe depression symptoms recorded at screening (HADS score ≥ 11).&#xD;
&#xD;
          2. Organic, including symptomatic, mental disorders (F00-09).&#xD;
&#xD;
          3. Mental and behavioural disorders due to psychoactive substance use (F10-19).&#xD;
&#xD;
          4. Schizophrenia, schizotypal and delusional disorders (F20-29).&#xD;
&#xD;
          5. Mood [affective] disorders(F30-39).&#xD;
&#xD;
          6. Phobic (F40) and other anxiety disorders (F41), obsessive-compulsive disorder (F42),&#xD;
             dissociative [conversion] disorders (F44), depersonalization-derealization syndrome&#xD;
             (F48.1).&#xD;
&#xD;
          7. Behavioral syndromes associated with physiological disturbances and physical factors&#xD;
             (F50-59).&#xD;
&#xD;
          8. Disorders of adult personality and behavior (F60-69).&#xD;
&#xD;
          9. Intellectual disabilities (F70-79).&#xD;
&#xD;
         10. Inflammatory and traumatic brain injuries with permanent neurological deficit.&#xD;
&#xD;
         11. Prior diagnosis of a class III or IV cardiovascular disease (according to the New York&#xD;
             Heart Association, 1964)&#xD;
&#xD;
         12. Malignant neoplasms/suspected malignant neoplasms.&#xD;
&#xD;
         13. An allergy/intolerance to any of the components of medications used in the treatment.&#xD;
&#xD;
         14. Malabsorption syndrome (including hereditary or acquired lactase or other&#xD;
             disaccharidase deficiency) and galactosemia.&#xD;
&#xD;
         15. Any conditions that, from investigator's point of view, may affect the patient's&#xD;
             ability to participate in the trial.&#xD;
&#xD;
         16. Hospitalizations or surgeries scheduled for any date during the participation in the&#xD;
             study.&#xD;
&#xD;
         17. Patients who, from investigator's point of view, will fail to comply with the&#xD;
             observation requirements of the trial or with the dosing regimen of the study drugs.&#xD;
&#xD;
         18. Use of drugs listed in &quot;Prohibited therapy&quot; within a month prior to enrollment.&#xD;
&#xD;
         19. Drug addiction, alcohol use in the amount over 2 units of alcohol a day.&#xD;
&#xD;
         20. Pregnant or breast-feeding women.&#xD;
&#xD;
         21. Participation in other clinical trials within 3 month prior to the enrollment in this&#xD;
             study.&#xD;
&#xD;
         22. Patients are related to the research personnel of the investigative site who are&#xD;
             directly involved in the trial, or patients who are the immediate family member of the&#xD;
             researcher. The 'immediate family member' includes husband/wife, parents, children or&#xD;
             brothers (or sisters), regardless of whether they are natural or adopted.&#xD;
&#xD;
         23. Patients working for OOO &quot;NPF &quot;MATERIA MEDICA HOLDING&quot;, i.e. the company's employee,&#xD;
             temporary contract worker, or appointed official responsible for carrying out the&#xD;
             research (or the immediate relative).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Vladimir Parfenov, DrMedSci</last_name>
    <role>Principal Investigator</role>
    <affiliation>I.M. Sechenov First Moscow State Medical University (Sechenov University)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Kazakh National Medical University named after S.D. Asfendiyarov</name>
      <address>
        <city>Almaty</city>
        <zip>050000</zip>
        <country>Kazakhstan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>South - Kazakhstan State Pharmaceutical Academy</name>
      <address>
        <city>Shymkent</city>
        <zip>160019</zip>
        <country>Kazakhstan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Municipal Autonomous Healthcare Institution Order of the Red Banner of Labor City Clinical Hospital No. 1</name>
      <address>
        <city>Chelyabinsk</city>
        <zip>454048</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Federal State Budgetary Educational Institution of Higher Education &quot;Kazan Medical University&quot; of the Ministry of Healthcare of the Russian Federation</name>
      <address>
        <city>Kazan'</city>
        <zip>420012</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The State Autonomic Health Care institution &quot;Interregional clinical and diagnostical center&quot;</name>
      <address>
        <city>Kazan'</city>
        <zip>420101</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LLC &quot;City Center for Neurology and Pain Management&quot;</name>
      <address>
        <city>Kazan'</city>
        <zip>420110</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Limited Liability Company &quot;Family policlinic no. 4&quot;</name>
      <address>
        <city>Korolev</city>
        <zip>141060</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Budget Health Care institution of Moscow the City &quot;Scientific and practical psychoneurological center n.a. Z.P. Solovyov&quot; of the Administration of Health Care of Moscow City</name>
      <address>
        <city>Moscow</city>
        <zip>115419</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The State Budget Health Care institution of Moscow the City &quot;City clinical hospital No. 12 of the Administration of Health Care of Moscow City&quot;</name>
      <address>
        <city>Moscow</city>
        <zip>115516</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pirogov Russian National Research Medical University</name>
      <address>
        <city>Moscow</city>
        <zip>117997</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The State Budget Educational institution of High Professional Training I.M. Sechenov First Moscow State Medical University of Ministry of Health Care of the Russian Federation, Hospital of nervous diseases A.Y. Kozhevnikov</name>
      <address>
        <city>Moscow</city>
        <zip>119992</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State budgetary institution of public health services of the Nizhniy Novgorod region &quot;Nizhegorod Regional Clinical Hospital named after NA Semashko&quot;</name>
      <address>
        <city>Nizhny Novgorod</city>
        <zip>603126</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LLC &quot;City Neurological Center&quot; Sibneyromed &quot;</name>
      <address>
        <city>Novosibirsk</city>
        <zip>630064</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pavlov First Saint Petersburg State Medical University/Department of Neurology and Manual Medicine</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>197022</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pavlov First Saint Petersburg State Medical University/Department of Neurology with Clinic</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>197022</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State-Funded Healthcare Institution of the Samara Region &quot;Samara City N.I. Pirogov Clinical Hospital №1&quot;</name>
      <address>
        <city>Samara</city>
        <zip>443096</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saratov State Medical University named after V. I. Razumovsky</name>
      <address>
        <city>Saratov</city>
        <zip>410012</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The State Budget Educational institution of High Professional Training Smolensk State Medical University of Ministry of Health Care of the Russian Federation, Smolensk regional clinical hospital</name>
      <address>
        <city>Smolensk</city>
        <zip>214018</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The state budgetary health care institution of the Vladimir region &quot;Regional Clinical Hospital&quot;</name>
      <address>
        <city>Vladimir</city>
        <zip>600023</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Volgograd State Medical University</name>
      <address>
        <city>Volgograd</city>
        <zip>400131</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The State Health Care Institution Yaroslavl region &quot;Clinical Hospital №8</name>
      <address>
        <city>Yaroslavl'</city>
        <zip>150030</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Institution of Health of the Yaroslavl Region Clinical Hospital No. 8</name>
      <address>
        <city>Yaroslavl</city>
        <zip>150030</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Kazakhstan</country>
    <country>Russian Federation</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>January 26, 2017</study_first_submitted>
  <study_first_submitted_qc>January 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 30, 2017</study_first_posted>
  <results_first_submitted>September 9, 2020</results_first_submitted>
  <results_first_submitted_qc>December 3, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">December 31, 2020</results_first_posted>
  <last_update_submitted>December 3, 2020</last_update_submitted>
  <last_update_submitted_qc>December 3, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 31, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neurotic Disorders</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>April 19, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/93/NCT03036293/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Tenoten, 2 Tablets Twice Daily (4 Tablets/Day)</title>
          <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in the mouth until dissolution, without meal.&#xD;
Tenoten: Tablet for oral use.</description>
        </group>
        <group group_id="P2">
          <title>Placebo, 2 Tablets Twice Daily (4 Tablets/Day)</title>
          <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in the mouth until dissolution, without meal.&#xD;
Placebo: Tablet for oral use.</description>
        </group>
        <group group_id="P3">
          <title>Tenoten, 2 Tablets 4 Times Daily (8 Tablets/Day)</title>
          <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets 4 times daily (8 tablets/days). The tablets should be held in the mouth until dissolution, without meal.&#xD;
Tenoten: Tablet for oral use.</description>
        </group>
        <group group_id="P4">
          <title>Placebo, 2 Tablets 4 Times Daily (8 Tablets/Day)</title>
          <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets 4 times daily (8 tablets/days). The tablets should be held in the mouth until dissolution, without meal.&#xD;
Placebo: Tablet for oral use.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="127"/>
                <participants group_id="P2" count="67"/>
                <participants group_id="P3" count="131"/>
                <participants group_id="P4" count="65"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="126"/>
                <participants group_id="P2" count="64"/>
                <participants group_id="P3" count="130"/>
                <participants group_id="P4" count="64"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Tenoten, 2 Tablets Twice Daily (4 Tablets/Day)</title>
          <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in the mouth until dissolution, without meal.&#xD;
Tenoten: Tablet for oral use.</description>
        </group>
        <group group_id="B2">
          <title>Placebo, 2 Tablets Twice Daily (4 Tablets/Day)</title>
          <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in the mouth until dissolution, without meal.&#xD;
Placebo: Tablet for oral use.</description>
        </group>
        <group group_id="B3">
          <title>Tenoten, 2 Tablets 4 Times Daily (8 Tablets/Day)</title>
          <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets 4 times daily (8 tablets/days). The tablets should be held in the mouth until dissolution, without meal.&#xD;
Tenoten: Tablet for oral use.</description>
        </group>
        <group group_id="B4">
          <title>Placebo, 2 Tablets 4 Times Daily (8 Tablets/Day)</title>
          <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets 4 times daily (8 tablets/days). The tablets should be held in the mouth until dissolution, without meal.&#xD;
Placebo: Tablet for oral use.</description>
        </group>
        <group group_id="B5">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="127"/>
            <count group_id="B2" value="67"/>
            <count group_id="B3" value="131"/>
            <count group_id="B4" value="65"/>
            <count group_id="B5" value="390"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="127"/>
                    <count group_id="B2" value="67"/>
                    <count group_id="B3" value="131"/>
                    <count group_id="B4" value="65"/>
                    <count group_id="B5" value="390"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="127"/>
                    <measurement group_id="B2" value="67"/>
                    <measurement group_id="B3" value="131"/>
                    <measurement group_id="B4" value="65"/>
                    <measurement group_id="B5" value="390"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="127"/>
                    <count group_id="B2" value="67"/>
                    <count group_id="B3" value="131"/>
                    <count group_id="B4" value="65"/>
                    <count group_id="B5" value="390"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="32.7" spread="7.1"/>
                    <measurement group_id="B2" value="34.2" spread="7.4"/>
                    <measurement group_id="B3" value="32.8" spread="7.6"/>
                    <measurement group_id="B4" value="34.8" spread="8"/>
                    <measurement group_id="B5" value="33.4" spread="7.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="127"/>
                    <count group_id="B2" value="67"/>
                    <count group_id="B3" value="131"/>
                    <count group_id="B4" value="65"/>
                    <count group_id="B5" value="390"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="99"/>
                    <measurement group_id="B2" value="50"/>
                    <measurement group_id="B3" value="102"/>
                    <measurement group_id="B4" value="52"/>
                    <measurement group_id="B5" value="303"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="29"/>
                    <measurement group_id="B4" value="13"/>
                    <measurement group_id="B5" value="87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="0"/>
                    <count group_id="B5" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Kazakhstan</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="127"/>
                    <count group_id="B2" value="67"/>
                    <count group_id="B3" value="131"/>
                    <count group_id="B4" value="65"/>
                    <count group_id="B5" value="390"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Russia</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="127"/>
                    <count group_id="B2" value="67"/>
                    <count group_id="B3" value="131"/>
                    <count group_id="B4" value="65"/>
                    <count group_id="B5" value="390"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="121"/>
                    <measurement group_id="B2" value="61"/>
                    <measurement group_id="B3" value="122"/>
                    <measurement group_id="B4" value="63"/>
                    <measurement group_id="B5" value="367"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>HAM-A scale baseline score</title>
          <description>The Hamilton Anxiety Rating Scale (HAM-A). Personality questionnaire designed to identify constitutive anxiety and situational anxiety. The scale consists of 14 items and measures both psychic anxiety and somatic anxiety. Total score is in range 0-56. Includes the symptoms of anxious mood, phobic, emotional, sleep disorders, depressive mood, somatic symptoms - muscular, sensory, cardiovascular, respiratory, gastrointestinal, genitourinary, neurovegetative.&#xD;
Anxiety scoring:&#xD;
≤13 - no anxiety; 14-17 - mild anxiety disorder; 18-24 - moderate anxiety disorder;&#xD;
≥25 - severe anxiety.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="127"/>
                    <count group_id="B2" value="67"/>
                    <count group_id="B3" value="131"/>
                    <count group_id="B4" value="65"/>
                    <count group_id="B5" value="390"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18.84" spread="5.81"/>
                    <measurement group_id="B2" value="17.69" spread="5.1"/>
                    <measurement group_id="B3" value="18.53" spread="4.32"/>
                    <measurement group_id="B4" value="18.2" spread="6.02"/>
                    <measurement group_id="B5" value="18.43" spread="5.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>EQ-5D-3L baseline score</title>
          <description>EQ-5D-3L questionnaire (European Quality of Life Instrument). Raw score range 5-15. The lower the better.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="127"/>
                    <count group_id="B2" value="67"/>
                    <count group_id="B3" value="131"/>
                    <count group_id="B4" value="65"/>
                    <count group_id="B5" value="390"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7.44" spread="1.44"/>
                    <measurement group_id="B2" value="7.51" spread="1.13"/>
                    <measurement group_id="B3" value="7.42" spread="1.05"/>
                    <measurement group_id="B4" value="7.47" spread="1.45"/>
                    <measurement group_id="B5" value="7.45" spread="1.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Hospital Anxiety and Depression Scale (HADS)-Anxiety</title>
          <description>Hospital Anxiety and Depression Scale - Anxiety subscale. Total score 0-21. The lower the better.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="127"/>
                    <count group_id="B2" value="67"/>
                    <count group_id="B3" value="131"/>
                    <count group_id="B4" value="65"/>
                    <count group_id="B5" value="390"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13.52" spread="1.79"/>
                    <measurement group_id="B2" value="13.01" spread="1.6"/>
                    <measurement group_id="B3" value="13.49" spread="1.79"/>
                    <measurement group_id="B4" value="13.46" spread="1.99"/>
                    <measurement group_id="B5" value="13.41" spread="1.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in the Mean HAM-A Score at 12 Weeks of Treatment: 1. Group 1 (Tenoten®, 4 Tablets a Day); 2. Group 3 (Tenoten®, 8 Tablets a Day).</title>
        <description>The Hamilton Anxiety Rating Scale (HAM-A). Personality questionnaire designed to identify constitutive anxiety and situational anxiety. The scale consists of 14 items and measures both psychic anxiety and somatic anxiety. Total score is in range 0-56. Includes the symptoms of anxious mood, phobic, emotional, sleep disorders, depressive mood, somatic symptoms - muscular (pain, convulsions, etc.), sensory (e.g. tinnitus), cardiovascular, respiratory, gastrointestinal, genitourinary, neurovegetative. Major role belongs to behaviour during this interview.&#xD;
Anxiety scoring:&#xD;
≤13 - no anxiety; 14-17 - mild anxiety disorder; 18-24 - moderate anxiety disorder;&#xD;
≥25 - severe anxiety.&#xD;
Higher values represent a worse outcome</description>
        <time_frame>12 weeks</time_frame>
        <population>Raw data from groups placebo-2 and placebo-4 was pooled into combined Placebo group. In accordance with study protocol no dose dependency in placebo effect was assumed. In accordance with study protocol no regiment dependency in placebo effect was assumed.</population>
        <group_list>
          <group group_id="O1">
            <title>Tenoten, 2 Tablets Twice Daily (4 Tablets/Day)</title>
            <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in the mouth until dissolution, without meal.&#xD;
Tenoten: Tablet for oral use.</description>
          </group>
          <group group_id="O2">
            <title>Tenoten, 2 Tablets 4 Times Daily (8 Tablets/Day)</title>
            <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets 4 times daily (8 tablets/days). The tablets should be held in the mouth until dissolution, without meal.&#xD;
Tenoten: Tablet for oral use.</description>
          </group>
          <group group_id="O3">
            <title>Placebo-2 + Placebo-4</title>
            <description>Placebo-2 (2 tablets twice daily) and Placebo-4 (2 tablets 4 times daily)</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Mean HAM-A Score at 12 Weeks of Treatment: 1. Group 1 (Tenoten®, 4 Tablets a Day); 2. Group 3 (Tenoten®, 8 Tablets a Day).</title>
          <description>The Hamilton Anxiety Rating Scale (HAM-A). Personality questionnaire designed to identify constitutive anxiety and situational anxiety. The scale consists of 14 items and measures both psychic anxiety and somatic anxiety. Total score is in range 0-56. Includes the symptoms of anxious mood, phobic, emotional, sleep disorders, depressive mood, somatic symptoms - muscular (pain, convulsions, etc.), sensory (e.g. tinnitus), cardiovascular, respiratory, gastrointestinal, genitourinary, neurovegetative. Major role belongs to behaviour during this interview.&#xD;
Anxiety scoring:&#xD;
≤13 - no anxiety; 14-17 - mild anxiety disorder; 18-24 - moderate anxiety disorder;&#xD;
≥25 - severe anxiety.&#xD;
Higher values represent a worse outcome</description>
          <population>Raw data from groups placebo-2 and placebo-4 was pooled into combined Placebo group. In accordance with study protocol no dose dependency in placebo effect was assumed. In accordance with study protocol no regiment dependency in placebo effect was assumed.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="126"/>
                <count group_id="O2" value="130"/>
                <count group_id="O3" value="128"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.81" spread="5.81"/>
                    <measurement group_id="O2" value="18.38" spread="4.32"/>
                    <measurement group_id="O3" value="17.88" spread="5.42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.26" spread="4.63"/>
                    <measurement group_id="O2" value="6.40" spread="4.02"/>
                    <measurement group_id="O3" value="8.48" spread="5.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Mean score differences (begin-end) were compared</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0055</p_value>
            <method>ANCOVA</method>
            <method_desc>Baseline score used as covariate</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>1.56</param_value>
            <ci_percent>98.33</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.217</ci_lower_limit>
            <ci_upper_limit>2.91</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Mean score differences (begin-end) were compared</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>ANCOVA</method>
            <method_desc>Baseline score used as covariate. Yeo-Johnson transformation with λ=1,09 was applied. Statistical inference performed for transformed values.</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>2.56</param_value>
            <ci_percent>98.33</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.1</ci_lower_limit>
            <ci_upper_limit>3.96</ci_upper_limit>
            <estimate_desc>estimate and CL are backtransformed</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Mean score differences (begin-end) were compared</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>equivalence limits were prespecified as [-2.763; 2.763]</non_inferiority_desc>
            <p_value>0.0008</p_value>
            <method>ANCOVA</method>
            <method_desc>Baseline score used as covariate</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.89</param_value>
            <ci_percent>98.33</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.64</ci_lower_limit>
            <ci_upper_limit>2.33</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Mean HAM-A Score at 4 Weeks of Treatment: 1.1. Group 1 (Tenoten®, 4 Tablets a Day); 1.2. Group 3 (Tenoten®, 8 Tablets a Day).</title>
        <description>The Hamilton Anxiety Rating Scale (HAM-A). Personality questionnaire designed to identify constitutive anxiety and situational anxiety. The scale consists of 14 items and measures both psychic anxiety and somatic anxiety. Total score is in range 0-56. Includes the symptoms of anxious mood, phobic, emotional, sleep disorders, depressive mood, somatic symptoms - muscular (pain, convulsions, etc.), sensory (e.g. tinnitus), cardiovascular, respiratory, gastrointestinal, genitourinary, neurovegetative. Major role belongs to behaviour during this interview.&#xD;
Anxiety scoring:&#xD;
≤13 - no anxiety; 14-17 - mild anxiety disorder; 18-24 - moderate anxiety disorder;&#xD;
≥25 - severe anxiety.&#xD;
Higher values represent a worse outcome</description>
        <time_frame>4 weeks</time_frame>
        <population>Raw data from groups placebo-2 and placebo-4 was pooled into combined Placebo group. In accordance with study protocol no dose dependency in placebo effect was assumed. In accordance with study protocol no regiment dependency in placebo effect was assumed.</population>
        <group_list>
          <group group_id="O1">
            <title>Tenoten, 2 Tablets Twice Daily (4 Tablets/Day)</title>
            <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in the mouth until dissolution, without meal.&#xD;
Tenoten: Tablet for oral use.</description>
          </group>
          <group group_id="O2">
            <title>Tenoten, 2 Tablets 4 Times Daily (8 Tablets/Day)</title>
            <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets 4 times daily (8 tablets/days). The tablets should be held in the mouth until dissolution, without meal.&#xD;
Tenoten: Tablet for oral use.</description>
          </group>
          <group group_id="O3">
            <title>Placebo-2 + Placebo-4</title>
            <description>Placebo-2 (2 tablets twice daily) and Placebo-4 (2 tablets 4 times daily)</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Mean HAM-A Score at 4 Weeks of Treatment: 1.1. Group 1 (Tenoten®, 4 Tablets a Day); 1.2. Group 3 (Tenoten®, 8 Tablets a Day).</title>
          <description>The Hamilton Anxiety Rating Scale (HAM-A). Personality questionnaire designed to identify constitutive anxiety and situational anxiety. The scale consists of 14 items and measures both psychic anxiety and somatic anxiety. Total score is in range 0-56. Includes the symptoms of anxious mood, phobic, emotional, sleep disorders, depressive mood, somatic symptoms - muscular (pain, convulsions, etc.), sensory (e.g. tinnitus), cardiovascular, respiratory, gastrointestinal, genitourinary, neurovegetative. Major role belongs to behaviour during this interview.&#xD;
Anxiety scoring:&#xD;
≤13 - no anxiety; 14-17 - mild anxiety disorder; 18-24 - moderate anxiety disorder;&#xD;
≥25 - severe anxiety.&#xD;
Higher values represent a worse outcome</description>
          <population>Raw data from groups placebo-2 and placebo-4 was pooled into combined Placebo group. In accordance with study protocol no dose dependency in placebo effect was assumed. In accordance with study protocol no regiment dependency in placebo effect was assumed.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="126"/>
                <count group_id="O2" value="130"/>
                <count group_id="O3" value="128"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.81" spread="5.81"/>
                    <measurement group_id="O2" value="18.38" spread="4.32"/>
                    <measurement group_id="O3" value="17.88" spread="5.42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.73" spread="5.35"/>
                    <measurement group_id="O2" value="13.31" spread="4.7"/>
                    <measurement group_id="O3" value="13.85" spread="5.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Mean score differences (begin-end) were compared</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.08</p_value>
            <method>ANCOVA</method>
            <method_desc>Baseline score used as covariate</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.08</ci_lower_limit>
            <ci_upper_limit>1.54</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Mean score differences (begin-end) were compared</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.044</p_value>
            <method>ANCOVA</method>
            <method_desc>Baseline score used as covariate</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.76</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.02</ci_lower_limit>
            <ci_upper_limit>1.66</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Mean HAM-A Score at 8 Weeks of Treatment: 2.1. Group 1 (Tenoten®, 4 Tablets a Day); 2.2. Group 3 (Tenoten®, 8 Tablets a Day).</title>
        <description>The Hamilton Anxiety Rating Scale (HAM-A). Personality questionnaire designed to identify constitutive anxiety and situational anxiety. The scale consists of 14 items and measures both psychic anxiety and somatic anxiety. Total score is in range 0-56. Includes the symptoms of anxious mood, phobic, emotional, sleep disorders, depressive mood, somatic symptoms - muscular (pain, convulsions, etc.), sensory (e.g. tinnitus), cardiovascular, respiratory, gastrointestinal, genitourinary, neurovegetative. Major role belongs to behaviour during this interview.&#xD;
Anxiety scoring:&#xD;
≤13 - no anxiety; 14-17 - mild anxiety disorder; 18-24 - moderate anxiety disorder;&#xD;
≥25 - severe anxiety.&#xD;
Higher values represent a worse outcome</description>
        <time_frame>8 weeks</time_frame>
        <population>Raw data from groгps placebo-2 and placebo-4 was pooled into combined Placebo group. In accordance with study protocol no dose dependency in placebo effect was assumed. In accordance with study protocol no regiment dependency in placebo effect was assumed.</population>
        <group_list>
          <group group_id="O1">
            <title>Tenoten, 2 Tablets Twice Daily (4 Tablets/Day)</title>
            <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in the mouth until dissolution, without meal.&#xD;
Tenoten: Tablet for oral use.</description>
          </group>
          <group group_id="O2">
            <title>Tenoten, 2 Tablets 4 Times Daily (8 Tablets/Day)</title>
            <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets 4 times daily (8 tablets/days). The tablets should be held in the mouth until dissolution, without meal.&#xD;
Tenoten: Tablet for oral use.</description>
          </group>
          <group group_id="O3">
            <title>Placebo-2 + Placebo-4</title>
            <description>Placebo-2 (2 tablets twice daily) and Placebo-4 (2 tablets 4 times daily)</description>
          </group>
        </group_list>
        <measure>
          <title>The Mean HAM-A Score at 8 Weeks of Treatment: 2.1. Group 1 (Tenoten®, 4 Tablets a Day); 2.2. Group 3 (Tenoten®, 8 Tablets a Day).</title>
          <description>The Hamilton Anxiety Rating Scale (HAM-A). Personality questionnaire designed to identify constitutive anxiety and situational anxiety. The scale consists of 14 items and measures both psychic anxiety and somatic anxiety. Total score is in range 0-56. Includes the symptoms of anxious mood, phobic, emotional, sleep disorders, depressive mood, somatic symptoms - muscular (pain, convulsions, etc.), sensory (e.g. tinnitus), cardiovascular, respiratory, gastrointestinal, genitourinary, neurovegetative. Major role belongs to behaviour during this interview.&#xD;
Anxiety scoring:&#xD;
≤13 - no anxiety; 14-17 - mild anxiety disorder; 18-24 - moderate anxiety disorder;&#xD;
≥25 - severe anxiety.&#xD;
Higher values represent a worse outcome</description>
          <population>Raw data from groгps placebo-2 and placebo-4 was pooled into combined Placebo group. In accordance with study protocol no dose dependency in placebo effect was assumed. In accordance with study protocol no regiment dependency in placebo effect was assumed.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="126"/>
                <count group_id="O2" value="130"/>
                <count group_id="O3" value="128"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.81" spread="5.81"/>
                    <measurement group_id="O2" value="18.38" spread="4.32"/>
                    <measurement group_id="O3" value="17.88" spread="5.42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.61" spread="5.44"/>
                    <measurement group_id="O2" value="9.88" spread="4.93"/>
                    <measurement group_id="O3" value="10.81" spread="5.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Mean score differences (begin-end) were compared</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.21</p_value>
            <method>ANCOVA</method>
            <method_desc>Baseline score used as covariate</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.69</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.4</ci_lower_limit>
            <ci_upper_limit>1.78</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Mean score differences (begin-end) were compared</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.027</p_value>
            <method>ANCOVA</method>
            <method_desc>Baseline score used as covariate</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>1.19</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.14</ci_lower_limit>
            <ci_upper_limit>2.26</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Patients Had at Least a 50% Improvement in the HAM-A Score: 3.1. Group 1 (Tenoten® 4 Tablets a Day): After 4, 8 and 12 Weeks; 3.2. Group 3 (Tenoten® 8 Tablets a Day): After 4, 8 and 12 Weeks.</title>
        <description>The Hamilton Anxiety Rating Scale (HAM-A). Personality questionnaire designed to identify constitutive anxiety and situational anxiety. The scale consists of 14 items and measures both psychic anxiety and somatic anxiety. Total score is in range 0-56. Includes the symptoms of anxious mood, phobic, emotional, sleep disorders, depressive mood, somatic symptoms - muscular (pain, convulsions, etc.), sensory (e.g. tinnitus), cardiovascular, respiratory, gastrointestinal, genitourinary, neurovegetative. Major role belongs to behaviour during this interview.&#xD;
Anxiety scoring:&#xD;
≤13 - no anxiety; 14-17 - mild anxiety disorder; 18-24 - moderate anxiety disorder;&#xD;
≥25 - severe anxiety.&#xD;
Higher values represent a worse outcome</description>
        <time_frame>4,8,12 weeks</time_frame>
        <population>Raw data from groups placebo-2 and placebo-4 was pooled into combined Placebo group. In accordance with study protocol no dose dependency in placebo effect was assumed. In accordance with study protocol no regiment dependency in placebo effect was assumed.</population>
        <group_list>
          <group group_id="O1">
            <title>Tenoten, 2 Tablets Twice Daily (4 Tablets/Day)</title>
            <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in the mouth until dissolution, without meal.&#xD;
Tenoten: Tablet for oral use.</description>
          </group>
          <group group_id="O2">
            <title>Tenoten, 2 Tablets 4 Times Daily (8 Tablets/Day)</title>
            <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets 4 times daily (8 tablets/days). The tablets should be held in the mouth until dissolution, without meal.&#xD;
Tenoten: Tablet for oral use.</description>
          </group>
          <group group_id="O3">
            <title>Placebo-2 + Placebo-4</title>
            <description>Placebo-2 (2 tablets twice daily) and Placebo-4 (2 tablets 4 times daily)</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients Had at Least a 50% Improvement in the HAM-A Score: 3.1. Group 1 (Tenoten® 4 Tablets a Day): After 4, 8 and 12 Weeks; 3.2. Group 3 (Tenoten® 8 Tablets a Day): After 4, 8 and 12 Weeks.</title>
          <description>The Hamilton Anxiety Rating Scale (HAM-A). Personality questionnaire designed to identify constitutive anxiety and situational anxiety. The scale consists of 14 items and measures both psychic anxiety and somatic anxiety. Total score is in range 0-56. Includes the symptoms of anxious mood, phobic, emotional, sleep disorders, depressive mood, somatic symptoms - muscular (pain, convulsions, etc.), sensory (e.g. tinnitus), cardiovascular, respiratory, gastrointestinal, genitourinary, neurovegetative. Major role belongs to behaviour during this interview.&#xD;
Anxiety scoring:&#xD;
≤13 - no anxiety; 14-17 - mild anxiety disorder; 18-24 - moderate anxiety disorder;&#xD;
≥25 - severe anxiety.&#xD;
Higher values represent a worse outcome</description>
          <population>Raw data from groups placebo-2 and placebo-4 was pooled into combined Placebo group. In accordance with study protocol no dose dependency in placebo effect was assumed. In accordance with study protocol no regiment dependency in placebo effect was assumed.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="126"/>
                <count group_id="O2" value="130"/>
                <count group_id="O3" value="128"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                    <measurement group_id="O2" value="18"/>
                    <measurement group_id="O3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44"/>
                    <measurement group_id="O2" value="55"/>
                    <measurement group_id="O3" value="45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="88"/>
                    <measurement group_id="O2" value="96"/>
                    <measurement group_id="O3" value="69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Common OR of event analysis</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.065</p_value>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.36</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.98</ci_lower_limit>
            <ci_upper_limit>1.89</ci_upper_limit>
            <estimate_desc>Bigger OR is better</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Common OR of event analysis</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0015</p_value>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.68</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.22</ci_lower_limit>
            <ci_upper_limit>2.33</ci_upper_limit>
            <estimate_desc>Bigger OR is better</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Week 4 frequencies comparison</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.7</p_value>
            <method>Fisher Exact</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Week 8 frequencies comparison</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>1</p_value>
            <method>Fisher Exact</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Week 12 frequencies comparison</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.01</p_value>
            <method>Fisher Exact</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Week 4 frequencies comparison</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.57</p_value>
            <method>Fisher Exact</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Week 8 frequencies comparison</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.25</p_value>
            <method>Fisher Exact</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Week 12 frequencies comparison</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.001</p_value>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Patients With no Anxiety (HAM-A Score &lt;14) in: 4.1. Group 1 (Tenoten®, 4 Tablets a Day); After 4, 8 and 12 Weeks; 4.3. Group 3 (Tenoten®, 4 Tablets a Day); After 4, 8 and 12 Weeks.</title>
        <description>The Hamilton Anxiety Rating Scale (HAM-A). Personality questionnaire designed to identify constitutive anxiety and situational anxiety. The scale consists of 14 items and measures both psychic anxiety and somatic anxiety. Total score is in range 0-56. Includes the symptoms of anxious mood, phobic, emotional, sleep disorders, depressive mood, somatic symptoms - muscular (pain, convulsions, etc.), sensory (e.g. tinnitus), cardiovascular, respiratory, gastrointestinal, genitourinary, neurovegetative. Major role belongs to behaviour during this interview.&#xD;
Anxiety scoring:&#xD;
≤13 - no anxiety; 14-17 - mild anxiety disorder; 18-24 - moderate anxiety disorder;&#xD;
≥25 - severe anxiety.&#xD;
Higher values represent a worse outcome</description>
        <time_frame>4,8,12 weeks</time_frame>
        <population>Raw data from groups placebo-2 and placebo-4 was pooled into combined Placebo group. In accordance with study protocol no dose dependency in placebo effect was assumed. In accordance with study protocol no regiment dependency in placebo effect was assumed.</population>
        <group_list>
          <group group_id="O1">
            <title>Tenoten, 2 Tablets Twice Daily (4 Tablets/Day)</title>
            <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in the mouth until dissolution, without meal.&#xD;
Tenoten: Tablet for oral use.</description>
          </group>
          <group group_id="O2">
            <title>Tenoten, 2 Tablets 4 Times Daily (8 Tablets/Day)</title>
            <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets 4 times daily (8 tablets/days). The tablets should be held in the mouth until dissolution, without meal.&#xD;
Tenoten: Tablet for oral use.</description>
          </group>
          <group group_id="O3">
            <title>Placebo-2 + Placebo-4</title>
            <description>Placebo-2 (2 tablets twice daily) and Placebo-4 (2 tablets 4 times daily)</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients With no Anxiety (HAM-A Score &lt;14) in: 4.1. Group 1 (Tenoten®, 4 Tablets a Day); After 4, 8 and 12 Weeks; 4.3. Group 3 (Tenoten®, 4 Tablets a Day); After 4, 8 and 12 Weeks.</title>
          <description>The Hamilton Anxiety Rating Scale (HAM-A). Personality questionnaire designed to identify constitutive anxiety and situational anxiety. The scale consists of 14 items and measures both psychic anxiety and somatic anxiety. Total score is in range 0-56. Includes the symptoms of anxious mood, phobic, emotional, sleep disorders, depressive mood, somatic symptoms - muscular (pain, convulsions, etc.), sensory (e.g. tinnitus), cardiovascular, respiratory, gastrointestinal, genitourinary, neurovegetative. Major role belongs to behaviour during this interview.&#xD;
Anxiety scoring:&#xD;
≤13 - no anxiety; 14-17 - mild anxiety disorder; 18-24 - moderate anxiety disorder;&#xD;
≥25 - severe anxiety.&#xD;
Higher values represent a worse outcome</description>
          <population>Raw data from groups placebo-2 and placebo-4 was pooled into combined Placebo group. In accordance with study protocol no dose dependency in placebo effect was assumed. In accordance with study protocol no regiment dependency in placebo effect was assumed.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="126"/>
                <count group_id="O2" value="130"/>
                <count group_id="O3" value="128"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="58"/>
                    <measurement group_id="O2" value="63"/>
                    <measurement group_id="O3" value="66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="91"/>
                    <measurement group_id="O2" value="105"/>
                    <measurement group_id="O3" value="96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="111"/>
                    <measurement group_id="O2" value="125"/>
                    <measurement group_id="O3" value="111"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Common OR of event analysis</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.46</p_value>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>0.88</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.64</ci_lower_limit>
            <ci_upper_limit>1.23</ci_upper_limit>
            <estimate_desc>Bigger OR is better</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Common OR of event analysis</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.17</p_value>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.27</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.9</ci_lower_limit>
            <ci_upper_limit>1.79</ci_upper_limit>
            <estimate_desc>Bigger OR is better</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Week 4 frequencies comparison</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.38</p_value>
            <method>Fisher Exact</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Week 8 frequencies comparison</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.67</p_value>
            <method>Fisher Exact</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Week 12 frequencies comparison</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.85</p_value>
            <method>Fisher Exact</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Week 4 frequencies comparison</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.71</p_value>
            <method>Fisher Exact</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Week 8 frequencies comparison</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.29</p_value>
            <method>Fisher Exact</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Week 12 frequencies comparison</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.007</p_value>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Total EQ-5D-3L Score at 12 Weeks of Treatment in Patients From: 5.1. Group 1 (Tenoten®, 4 Tablets a Day); 5.2. Group 3 (Tenoten®, 8 Tablets a Day).</title>
        <description>European Quality of Life Instrument questionnaire (EQ-5D-3L) is designed for the evaluation of the quality of life.The score ranges between 5-15. Higher values represent a worse outcome.</description>
        <time_frame>12 weeks</time_frame>
        <population>Raw data from groups placebo-2 and placebo-4 was pooled into combined Placebo group. In accordance with study protocol no dose dependency in placebo effect was assumed. In accordance with study protocol no regiment dependency in placebo effect was assumed.</population>
        <group_list>
          <group group_id="O1">
            <title>Tenoten, 2 Tablets Twice Daily (4 Tablets/Day)</title>
            <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in the mouth until dissolution, without meal.&#xD;
Tenoten: Tablet for oral use.</description>
          </group>
          <group group_id="O2">
            <title>Tenoten, 2 Tablets 4 Times Daily (8 Tablets/Day)</title>
            <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets 4 times daily (8 tablets/days). The tablets should be held in the mouth until dissolution, without meal.&#xD;
Tenoten: Tablet for oral use.</description>
          </group>
          <group group_id="O3">
            <title>Placebo-2 + Placebo-4</title>
            <description>Placebo-2 (2 tablets twice daily) and Placebo-4 (2 tablets 4 times daily)</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Total EQ-5D-3L Score at 12 Weeks of Treatment in Patients From: 5.1. Group 1 (Tenoten®, 4 Tablets a Day); 5.2. Group 3 (Tenoten®, 8 Tablets a Day).</title>
          <description>European Quality of Life Instrument questionnaire (EQ-5D-3L) is designed for the evaluation of the quality of life.The score ranges between 5-15. Higher values represent a worse outcome.</description>
          <population>Raw data from groups placebo-2 and placebo-4 was pooled into combined Placebo group. In accordance with study protocol no dose dependency in placebo effect was assumed. In accordance with study protocol no regiment dependency in placebo effect was assumed.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="126"/>
                <count group_id="O2" value="130"/>
                <count group_id="O3" value="128"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.44" spread="1.44"/>
                    <measurement group_id="O2" value="7.42" spread="1.05"/>
                    <measurement group_id="O3" value="7.48" spread="1.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.84" spread="1.05"/>
                    <measurement group_id="O2" value="5.71" spread="0.82"/>
                    <measurement group_id="O3" value="6.05" spread="1.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Median changes (begin-end) within groups are compared</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.314</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Median Difference (Net)</param_type>
            <param_value>0.00002</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.00002</ci_lower_limit>
            <ci_upper_limit>0.33</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimator for location difference provided</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Median changes (begin-end) within groups are compared</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.031</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Median Difference (Net)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>1</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimator for location difference provided</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total CGI Scores in Patients From: 6.1. Group 1 (Tenoten®, 4 Tablets a Day); 6.2. Group 3 (Tenoten®, 8 Tablets a Day).</title>
        <description>Clinical Global Impession (CGI) provides a brief assessment of the clinician's view of the patient's global functioning prior to and after initiating a study medication. Total range 0-16. Higher values represent a worse outcome</description>
        <time_frame>12 weeks</time_frame>
        <population>Raw data from groups placebo-2 and placebo-4 was pooled into combined Placebo group. In accordance with study protocol no dose dependency in placebo effect was assumed. In accordance with study protocol no regiment dependency in placebo effect was assumed.</population>
        <group_list>
          <group group_id="O1">
            <title>Tenoten, 2 Tablets Twice Daily (4 Tablets/Day)</title>
            <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in the mouth until dissolution, without meal.&#xD;
Tenoten: Tablet for oral use.</description>
          </group>
          <group group_id="O2">
            <title>Tenoten, 2 Tablets 4 Times Daily (8 Tablets/Day)</title>
            <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets 4 times daily (8 tablets/days). The tablets should be held in the mouth until dissolution, without meal.&#xD;
Tenoten: Tablet for oral use.</description>
          </group>
          <group group_id="O3">
            <title>Placebo-2 + Placebo-4</title>
            <description>Placebo-2 (2 tablets twice daily) and Placebo-4 (2 tablets 4 times daily)</description>
          </group>
        </group_list>
        <measure>
          <title>Total CGI Scores in Patients From: 6.1. Group 1 (Tenoten®, 4 Tablets a Day); 6.2. Group 3 (Tenoten®, 8 Tablets a Day).</title>
          <description>Clinical Global Impession (CGI) provides a brief assessment of the clinician's view of the patient's global functioning prior to and after initiating a study medication. Total range 0-16. Higher values represent a worse outcome</description>
          <population>Raw data from groups placebo-2 and placebo-4 was pooled into combined Placebo group. In accordance with study protocol no dose dependency in placebo effect was assumed. In accordance with study protocol no regiment dependency in placebo effect was assumed.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="126"/>
                <count group_id="O2" value="130"/>
                <count group_id="O3" value="128"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.53" spread="3.21"/>
                    <measurement group_id="O2" value="4.55" spread="2.91"/>
                    <measurement group_id="O3" value="5.71" spread="3.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0021</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Median Difference (Net)</param_type>
            <param_value>-0.00001</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3</ci_lower_limit>
            <ci_upper_limit>-0.00001</ci_upper_limit>
            <estimate_desc>Lower is better</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0056</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Median Difference (Net)</param_type>
            <param_value>-0.00002</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1</ci_lower_limit>
            <ci_upper_limit>-0.00002</ci_upper_limit>
            <estimate_desc>Lower is better</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>During the study (12 weeks).</time_frame>
      <desc>Adverse/Serious adverse events were registered in patients of the Safety population (n=390).</desc>
      <group_list>
        <group group_id="E1">
          <title>Tenoten, 2 Tablets Twice Daily (4 Tablets/Day)</title>
          <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in the mouth until dissolution, without meal.&#xD;
Tenoten: Tablet for oral use.</description>
        </group>
        <group group_id="E2">
          <title>Tenoten, 2 Tablets 4 Times Daily (8 Tablets/Day)</title>
          <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets 4 times daily (8 tablets/days). The tablets should be held in the mouth until dissolution, without meal.&#xD;
Tenoten: Tablet for oral use.</description>
        </group>
        <group group_id="E3">
          <title>Placebo-2 + Placebo-4</title>
          <description>Placebo-2 (2 tablets twice daily) and Placebo-4 (2 tablets 4 times daily)&#xD;
Raw data from groups placebo-2 and placebo-4 was pooled into combined Placebo group. In accordance with study protocol no dose dependency in placebo effect was assumed. In accordance with study protocol no regiment dependency in placebo effect was assumed.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="127"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="131"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="132"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="127"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="131"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="132"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="127"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="131"/>
                <counts group_id="E3" subjects_affected="17" subjects_at_risk="132"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="127"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="131"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="132"/>
              </event>
              <event>
                <sub_title>Supraventricular tachyarrhythmia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="127"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="131"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="132"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Photophobia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="127"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="131"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="132"/>
              </event>
              <event>
                <sub_title>Retinal vascular disorder</sub_title>
                <description>Retinal angiopathy</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="127"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="131"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="132"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="127"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="131"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="132"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="127"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="131"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="132"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bacterial vaginosis</sub_title>
                <description>Vaginosis bacterial NOS</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="127"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="131"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="132"/>
              </event>
              <event>
                <sub_title>Chronic sinusitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="127"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="131"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="132"/>
              </event>
              <event>
                <sub_title>Chronic tonsillitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="127"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="131"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="132"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="127"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="131"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="132"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="127"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="131"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="132"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="127"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="131"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="132"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="127"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="131"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="132"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="127"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="131"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="132"/>
              </event>
              <event>
                <sub_title>Tonsillitis</sub_title>
                <description>Acute tonsillitis</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="127"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="131"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="132"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Eye contusion</sub_title>
                <description>Periorbital contusion</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="127"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="131"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="132"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Heart rate increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="127"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="131"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="132"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <description>Lumbar pain</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="127"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="131"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="132"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <description>Cramps in legs (calf)</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="127"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="131"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="132"/>
              </event>
              <event>
                <sub_title>Osteochondrosis</sub_title>
                <description>Osteochondrosis of spine</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="127"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="131"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="132"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <description>Taste metallic</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="127"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="131"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="132"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <description>Headache NOS, temporal headache, headache unilateral, headache fullness</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="127"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="131"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="132"/>
              </event>
              <event>
                <sub_title>Occipital neuralgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="127"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="131"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="132"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <description>Daytime sleepiness, sleepiness</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="127"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="131"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="132"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="127"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="131"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="132"/>
              </event>
              <event>
                <sub_title>Panic attack</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="127"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="131"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="132"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Menstruation delayed</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="127"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="131"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="132"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nasal septum deviation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="127"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="131"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="132"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="127"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="131"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="132"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Mikhail Putilovskiy, MD, PhD, Clinical and Medical Department Director</name_or_title>
      <organization>Materia Medica Holding</organization>
      <phone>+74952761571 ext 302</phone>
      <email>PutilovskiyMA@materiamedica.ru</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03036293
org study id: MMH-TN-001
nct id: NCT03036293
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purposes of this study are:

        -  To further examine the efficacy and safety of Tenoten® in the treatment of anxiety in
           patients with somatoform, stress-related and other neurotic disorders.

        -  To compare the efficacy of two dosing regimens of Tenoten® (4 tablets daily vs.8 tablets
           daily, both for 12 weeks) in the treatment of anxiety in patients with somatoform,
           stress-related and other neurotic disorders.
Design: an international, a multicenter, double-blind, randomized, parallel group
      placebo-controlled trial to evaluate efficacy and safety of study treatment.

      The study will enroll outpatient subjects of both genders aged 18-45 years with verified
      diagnoses of somatoform, stress-related and other neurotic disorders (F43, F45, F48) and
      signs of clinically relevant anxiety according to The Hospital Anxiety and Depression scale
      (HADS).

      After signing the informed consent form to participate in the clinical study the subject will
      be interviewed (complaints, medical history, concomitant therapy) and objective examination
      will be performed; the subject will fill HADS scale. The severity of anxiety at screening
      should be ≥ 11 according to HADS. If the subject meets inclusion criteria and has no
      exclusion criteria he/she will be enrolled into the study. The investigator will determine
      the severity of anxiety using НАМ-А scale; the subject will fill EQ-5D-3L questionnaire. At
      Visit 1 (Day 1) the subject will be randomized into one of the treatment groups:

        -  Group 1: Tenoten® at 2 tablets twice daily (4 tablets/day);

        -  Group 2: Placebo at 2 tablets twice daily (4 tablets/day);

        -  Group 3: Tenoten® at 2 tablets 4 daily (8 tablets/day).

        -  Group 4: Placebo at 2 tablets 4 daily (8 tablets/day). The first dose should be
           administered at Visit 1 after the visit procedures are completed. Further administration
           of the study product will be made according to the dosing scheme. The subject will
           administer the study product and will be followed for 12 weeks during which additional
           three visits will be made. At Visit 2 (Week 4), Visit 3 (Week 8) and Visit 4 (Week 12)
           the physician will record patients' complaints and physical examination data, fill HAM-A
           scale, check the study and concomitant therapy, assess treatment safety and patient
           compliance with the study treatment. At the final Visit 4 the subject will fill EQ-5D-3L
           questionnaire and the investigator will fill the Clinical Global Impression Scale
           Efficacy Index (CGI-EI).

      Subjects will be allowed to take symptomatic therapy and medications for their co-morbidities
      during the study, except for the medicines listed in "Prohibited therapy".
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change From Baseline in the Mean HAM-A Score at 12 Weeks of Treatment: 1. Group 1 (Tenoten®, 4 Tablets a Day); 2. Group 3 (Tenoten®, 8 Tablets a Day).
time frame: 12 weeks
description: The Hamilton Anxiety Rating Scale (HAM-A). Personality questionnaire designed to identify constitutive anxiety and situational anxiety. The scale consists of 14 items and measures both psychic anxiety and somatic anxiety. Total score is in range 0-56. Includes the symptoms of anxious mood, phobic, emotional, sleep disorders, depressive mood, somatic symptoms - muscular (pain, convulsions, etc.), sensory (e.g. tinnitus), cardiovascular, respiratory, gastrointestinal, genitourinary, neurovegetative. Major role belongs to behaviour during this interview.
Anxiety scoring:
≤13 - no anxiety; 14-17 - mild anxiety disorder; 18-24 - moderate anxiety disorder;
≥25 - severe anxiety.
Higher values represent a worse outcome
measure: Change From Baseline in the Mean HAM-A Score at 4 Weeks of Treatment: 1.1. Group 1 (Tenoten®, 4 Tablets a Day); 1.2. Group 3 (Tenoten®, 8 Tablets a Day).
time frame: 4 weeks
description: The Hamilton Anxiety Rating Scale (HAM-A). Personality questionnaire designed to identify constitutive anxiety and situational anxiety. The scale consists of 14 items and measures both psychic anxiety and somatic anxiety. Total score is in range 0-56. Includes the symptoms of anxious mood, phobic, emotional, sleep disorders, depressive mood, somatic symptoms - muscular (pain, convulsions, etc.), sensory (e.g. tinnitus), cardiovascular, respiratory, gastrointestinal, genitourinary, neurovegetative. Major role belongs to behaviour during this interview.
Anxiety scoring:
≤13 - no anxiety; 14-17 - mild anxiety disorder; 18-24 - moderate anxiety disorder;
≥25 - severe anxiety.
Higher values represent a worse outcome
measure: The Mean HAM-A Score at 8 Weeks of Treatment: 2.1. Group 1 (Tenoten®, 4 Tablets a Day); 2.2. Group 3 (Tenoten®, 8 Tablets a Day).
time frame: 8 weeks
description: The Hamilton Anxiety Rating Scale (HAM-A). Personality questionnaire designed to identify constitutive anxiety and situational anxiety. The scale consists of 14 items and measures both psychic anxiety and somatic anxiety. Total score is in range 0-56. Includes the symptoms of anxious mood, phobic, emotional, sleep disorders, depressive mood, somatic symptoms - muscular (pain, convulsions, etc.), sensory (e.g. tinnitus), cardiovascular, respiratory, gastrointestinal, genitourinary, neurovegetative. Major role belongs to behaviour during this interview.
Anxiety scoring:
≤13 - no anxiety; 14-17 - mild anxiety disorder; 18-24 - moderate anxiety disorder;
≥25 - severe anxiety.
Higher values represent a worse outcome
measure: Percentage of Patients Had at Least a 50% Improvement in the HAM-A Score: 3.1. Group 1 (Tenoten® 4 Tablets a Day): After 4, 8 and 12 Weeks; 3.2. Group 3 (Tenoten® 8 Tablets a Day): After 4, 8 and 12 Weeks.
time frame: 4,8,12 weeks
description: The Hamilton Anxiety Rating Scale (HAM-A). Personality questionnaire designed to identify constitutive anxiety and situational anxiety. The scale consists of 14 items and measures both psychic anxiety and somatic anxiety. Total score is in range 0-56. Includes the symptoms of anxious mood, phobic, emotional, sleep disorders, depressive mood, somatic symptoms - muscular (pain, convulsions, etc.), sensory (e.g. tinnitus), cardiovascular, respiratory, gastrointestinal, genitourinary, neurovegetative. Major role belongs to behaviour during this interview.
Anxiety scoring:
≤13 - no anxiety; 14-17 - mild anxiety disorder; 18-24 - moderate anxiety disorder;
≥25 - severe anxiety.
Higher values represent a worse outcome
measure: Percentage of Patients With no Anxiety (HAM-A Score <14) in: 4.1. Group 1 (Tenoten®, 4 Tablets a Day); After 4, 8 and 12 Weeks; 4.3. Group 3 (Tenoten®, 4 Tablets a Day); After 4, 8 and 12 Weeks.
time frame: 4,8,12 weeks
description: The Hamilton Anxiety Rating Scale (HAM-A). Personality questionnaire designed to identify constitutive anxiety and situational anxiety. The scale consists of 14 items and measures both psychic anxiety and somatic anxiety. Total score is in range 0-56. Includes the symptoms of anxious mood, phobic, emotional, sleep disorders, depressive mood, somatic symptoms - muscular (pain, convulsions, etc.), sensory (e.g. tinnitus), cardiovascular, respiratory, gastrointestinal, genitourinary, neurovegetative. Major role belongs to behaviour during this interview.
Anxiety scoring:
≤13 - no anxiety; 14-17 - mild anxiety disorder; 18-24 - moderate anxiety disorder;
≥25 - severe anxiety.
Higher values represent a worse outcome
measure: Change From Baseline in the Total EQ-5D-3L Score at 12 Weeks of Treatment in Patients From: 5.1. Group 1 (Tenoten®, 4 Tablets a Day); 5.2. Group 3 (Tenoten®, 8 Tablets a Day).
time frame: 12 weeks
description: European Quality of Life Instrument questionnaire (EQ-5D-3L) is designed for the evaluation of the quality of life.The score ranges between 5-15. Higher values represent a worse outcome.
measure: Total CGI Scores in Patients From: 6.1. Group 1 (Tenoten®, 4 Tablets a Day); 6.2. Group 3 (Tenoten®, 8 Tablets a Day).
time frame: 12 weeks
description: Clinical Global Impession (CGI) provides a brief assessment of the clinician's view of the patient's global functioning prior to and after initiating a study medication. Total range 0-16. Higher values represent a worse outcome
arm group label: Tenoten, 2 tablets twice daily (4 tablets/day)
arm group type: Experimental
description: Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in the mouth until dissolution, without meal.
arm group label: Placebo, 2 tablets twice daily (4 tablets/day)
arm group type: Placebo Comparator
description: Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in the mouth until dissolution, without meal.
arm group label: Tenoten, 2 tablets 4 times daily (8 tablets/day)
arm group type: Experimental
description: Tablet for oral use. Dose per administration: 2 tablets. 2 tablets 4 times daily (8 tablets/days). The tablets should be held in the mouth until dissolution, without meal.
arm group label: Placebo, 2 tablets 4 times daily (8 tablets/day)
arm group type: Placebo Comparator
description: Tablet for oral use. Dose per administration: 2 tablets. 2 tablets 4 times daily (8 tablets/days). The tablets should be held in the mouth until dissolution, without meal.
intervention type: Drug
intervention name: Tenoten
description: Tablet for oral use.
arm group label: Tenoten, 2 tablets 4 times daily (8 tablets/day)
arm group label: Tenoten, 2 tablets twice daily (4 tablets/day)
intervention type: Drug
intervention name: Placebo
description: Tablet for oral use.
arm group label: Placebo, 2 tablets 4 times daily (8 tablets/day)
arm group label: Placebo, 2 tablets twice daily (4 tablets/day)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: No
last name: Vladimir Parfenov, DrMedSci
role: Principal Investigator
affiliation: I.M. Sechenov First Moscow State Medical University (Sechenov University)
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country: Kazakhstan
country: Russian Federation
responsible party type: Sponsor
mesh term: Neurotic Disorders
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 