<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/NCT03815292</url>
  </required_header>
  <id_info>
    <org_study_id>MMH-MAP-001</org_study_id>
    <nct_id>NCT03815292</nct_id>
  </id_info>
  <brief_title>Clinical Trial of Efficacy and Safety of MMH-MAP in the Treatment of Mild Cognitive Impairment in Early Recovery Stage After Ischemic Stroke</brief_title>
  <official_title>Multicenter Double-blind Placebo-controlled Randomized Parallel-group Clinical Study of Efficacy and Safety of MMH-MAP in the Treatment of Mild Cognitive Impairment in Subjects in Early Rehabilitation Period of Ischemic Stroke</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>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is:&#xD;
&#xD;
        -  to evaluate efficacy of MMH-MAP in the treatment of mild cognitive impairment in&#xD;
           subjects in early rehabilitation period of ischemic stroke&#xD;
&#xD;
        -  to evaluate safety of MMH-MAP in the treatment of mild cognitive impairment in subjects&#xD;
           in early rehabilitation period of ischemic stroke&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A double-blind, placebo-controlled randomized clinical trial in parallel groups.&#xD;
&#xD;
      The study patients are subjects of either gender, aged 45-80 years old, after an ischemic&#xD;
      stroke within 3-6 months prior to enrollment and confirmed by neuroimaging, having mild&#xD;
      cognitive impairment.&#xD;
&#xD;
      After the patients provide signed Participant Information Sheet and Informed Consent, they&#xD;
      will be interviewed for complaints and medical history and undergo physical examination and&#xD;
      laboratory tests. The doctor will rate the severity of patients' cognitive impairments on the&#xD;
      Mini Mental State Examination (MMSE) scale and Montreal Cognitive Assessment (MoCA) scale,&#xD;
      assess their performance in activities of daily living on the Barthel Index scale [Collin C,&#xD;
      Wade DT, Davies S, Horne V. &quot;The Barthel ADL Index: a reliability study.&quot; Int Disability&#xD;
      Study.1988;10:61-63.], and administer the Stroke Specific Quality of Life Scale (SS-QOL)&#xD;
      questionnaire [Williams LS, Weinberger M, Harris LE, Clark DO, Biller J. Development of a&#xD;
      stroke-specific quality of life scale. Stroke 1999 Jul;30(7):1362-9]. Eligible participants&#xD;
      will have to have moderate cognitive impairments (MMSE score - at least 21 and MoCA - less&#xD;
      than 26). Therapy received by patients for their co-morbidities and primary diagnosis will be&#xD;
      recorded. All women of childbearing potential will be administered pregnancy tests.&#xD;
&#xD;
      If a patient meets all inclusion criteria and does not have any exclusion criteria at Visit&#xD;
      1, he/she is randomized to one of the two groups: group 1 will receive MMH-MAP at 2 tablets&#xD;
      twice daily; group 2 will receive Placebo using the study product dosing regimen. The total&#xD;
      duration of follow-up and treatment will be 28 weeks, which will include 5 additional visits.&#xD;
&#xD;
      At Visit 2 (Week 4±7 days), the doctor records patients' complaints and physical examination&#xD;
      data, reviews the progress of study and basic and concomitant therapy, and assesses treatment&#xD;
      safety and patient compliance with treatment.&#xD;
&#xD;
      At Visit 3 (Week 8±7 days), Visit 4 (Week 16±7 days), and Visit 5 (Week 24±7 days), the&#xD;
      doctor assesses patients' cognitive impairments (MoCA) and performance in activities of daily&#xD;
      living (the Barthel Index). The patients complete the SS-QOL questionnaire.&#xD;
&#xD;
      At Visit 5 (Week 24±7 days), the doctor will additionally complete the Clinical Global&#xD;
      Impression Efficacy Index (CGI-EI) scale [Guy W, editor. ECDEU Assessment Manual for&#xD;
      Psychopharmacology. 1976 Rockville, MD, U.S. Department of Health, Education, and Welfare]&#xD;
      and collect samples for laboratory testing. The patient stops taking the study drug.&#xD;
&#xD;
      After four weeks following the end of study therapy patients complete a follow-up visit&#xD;
      -Visit 6 (Week 28±7 days). The patients are interviewed for complaints and undergo physical&#xD;
      examination, with a check on their concomitant and primary therapies as well as on the safety&#xD;
      of study treatment. The doctor assesses patients' cognitive impairments (MoCA) and&#xD;
      performance in activities of daily living (the Barthel Index) and administers the SS-QOL&#xD;
      questionnaire.&#xD;
&#xD;
      The total length of the observation period will be 28 weeks. During the study, symptomatic&#xD;
      therapy and therapy for underlying chronic conditions are allowed with the exception of the&#xD;
      drugs indicated in the section &quot;Prohibited Concomitant Treatment&quot;.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 19, 2018</start_date>
  <completion_date type="Actual">January 27, 2020</completion_date>
  <primary_completion_date type="Actual">January 27, 2020</primary_completion_date>
  <phase>Phase 3</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>Percentage of Patients With Improved Cognitive Function (The Montreal Cognitive Assessment Test Total Score of the Baseline +1 or More)</measure>
    <time_frame>24 weeks of the treatment as compared to the baseline</time_frame>
    <description>MoCa is the test for assessment of cognitive impairment. The score ranges between 0 and 30. A score of 26-30 is normal. A score less than 26 is considered as mild cognitive impairment. Higher values represent a better outcome.</description>
  </primary_outcome>
  <other_outcome>
    <measure>Change in MoCA (The Montreal Cognitive Assessment Test) Score</measure>
    <time_frame>24 weeks of the treatment as compared to the baseline</time_frame>
    <description>MoCa is the test for assessment of cognitive impairment. The score ranges between 0 and 30. A score of 26-30 is normal. A score less than 26 is considered as mild cognitive impairment. Higher values represent a better outcome.</description>
  </other_outcome>
  <other_outcome>
    <measure>Percentage of Patients With Improved Performance in Activities of Daily Living (Barthel Index Score of the Baseline + 5 or More)</measure>
    <time_frame>24 weeks of the treatment as compared to the baseline</time_frame>
    <description>Scale for measurement of performance in activities of daily living (ADL).The maximum score is 100. A score of 91-99 stands for mild dependence in ADL performance, 61-90 - for moderate dependence in ADL performance, 21-60 - for severe dependence in ADL performance, 0-20 - for complete dependence in ADL performance. Higher values represent a better outcome.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Barthel Index Score</measure>
    <time_frame>24 weeks of the treatment as compared to the baseline</time_frame>
    <description>Scale for measurement of performance in activities of daily living (ADL).The maximum score is 100. A score of 91-99 stands for mild dependence in ADL performance, 61-90 - for moderate dependence in ADL performance, 21-60 - for severe dependence in ADL performance, 0-20 - for complete dependence in ADL performance. Higher values represent a better outcome.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in SS-QOL (Stroke Specific Quality of Life Scale) Total Score</measure>
    <time_frame>24 weeks of the treatment as compared to the baseline</time_frame>
    <description>Scale for assessment of health-related quality of life. The scale consists of 49 items in the 12 domains. Each domain consists of 3 to 10 items that are averaged to generate an overall score. Total score minimum value is 1 and maximum value is 245. Higher values represent a better outcome.</description>
  </other_outcome>
  <other_outcome>
    <measure>The CGI-EI (Clinical Global Impression Efficacy Index) Score</measure>
    <time_frame>24 weeks of the treatment</time_frame>
    <description>Rating scale for assessment of the therapeutic effect of treatment and associated side effects. The scale consists of 2 items: therapeutic effect and side effects. Scores in therapeutic effect range from 1 (marked improvement) to 13 (unchanged or worse). Scores in side effects range from 0 (no side effects) to 3 (side effects outweigh therapeutic effects). Efficacy index ranges between 0 and 16. Higher values represent a worse result.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in MoCA (The Montreal Cognitive Assessment Test) Score During Follow-up</measure>
    <time_frame>24 and 28 weeks of the study</time_frame>
    <description>Test for assessment of cognitive impairment. The score ranges between 0 and 30. A score of 26-30 is normal. A score less than 26 is considered as mild cognitive impairment. Higher values represent a better outcome.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Barthel Index Score During Follow-up</measure>
    <time_frame>24 and 28 weeks of the study</time_frame>
    <description>Scale for measurement of performance in activities of daily living (ADL). The maximum score is 100. A score of 91-99 stands for mild dependence in ADL performance, 61-90 - for moderate dependence in ADL performance, 21-60 - for severe dependence in ADL performance, 0-20 - for complete dependence in ADL performance. Higher values represent a better outcome.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Total SS-QOL (Stroke Specific Quality of Life Scale) Score During Follow-up</measure>
    <time_frame>24 and 28 weeks of the study</time_frame>
    <description>Scale for assessment of health-related quality of life. The scale consists of 49 items in the 12 domains.Each domain consists of 3 to 10 items that are averaged to generate an overall score.Total score minimum value is 1 and maximum value is 245.Higher values represent a better outcome.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">276</enrollment>
  <condition>Mild Cognitive Impairment</condition>
  <condition>Ischemic Stroke</condition>
  <arm_group>
    <arm_group_label>MMH-MAP</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 mouth without chewing until complete dissolution. The duration of treatment will be 24 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo for 24 weeks, according to the MMH-MAP dosing regimen.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MMH-MAP</intervention_name>
    <description>Oral administration</description>
    <arm_group_label>MMH-MAP</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Oral administration</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients of either sex, aged 45 to 80 years old inclusively.&#xD;
&#xD;
          2. Patients with a history of one stroke sustained 3 to 6 months prior to study entry and&#xD;
             confirmed by neuroimaging.&#xD;
&#xD;
          3. Patients with cognitive impairment (MoCA score &lt; 26).&#xD;
&#xD;
          4. Patients with moderate performance in activities of daily living (Barthel score =&#xD;
             61-80).&#xD;
&#xD;
          5. Agreement to use a reliable method of birth control for the duration of the study (men&#xD;
             and women of reproductive potential).&#xD;
&#xD;
          6. Availability of signed patient information sheet (Informed Consent form) for&#xD;
             participation in the clinical trial.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with a history of subarachnoid/parenchymatous/ventricular hemorrhage, brain&#xD;
             neoplasm, or any other condition which has caused neurological dysfunction.&#xD;
&#xD;
          2. History of central nervous system (CNS) disorders, including:&#xD;
&#xD;
               -  inflammatory diseases of the CNS (G00-G09)&#xD;
&#xD;
               -  systemic atrophies primarily affecting the CNS (G10-G13)&#xD;
&#xD;
               -  extrapyramidal and movement disorders (G20-G26)&#xD;
&#xD;
               -  other degenerative diseases of the nervous system (G30-G32)&#xD;
&#xD;
               -  demyelinating diseases of the CNS (G35-G37)&#xD;
&#xD;
               -  epilepsy (G40-41)&#xD;
&#xD;
               -  polyneuropathies and other disorders of the peripheral nervous system (G60-64),&#xD;
                  with marked movement and/or sensory impairments that cause movement disorders&#xD;
&#xD;
               -  diseases of neuromuscular junction and muscle (G70-73)&#xD;
&#xD;
               -  hydrocephalus (G91)&#xD;
&#xD;
               -  compression of brain (G93.5).&#xD;
&#xD;
          3. Dementia (20 or less on the MMSE score).&#xD;
&#xD;
          4. Speech disorders affecting investigator-patient communication.&#xD;
&#xD;
          5. Prior diagnosis of heart failure defined by the New York Heart Association&#xD;
             classification (1964) as IV Functional Classification or poorly treated hypothyroidism&#xD;
             or diabetes mellitus.&#xD;
&#xD;
          6. Patients having unstable angina or myocardial infarction in the past 6 months.&#xD;
&#xD;
          7. History/suspicion of oncology of any location (except for benign neoplasms).&#xD;
&#xD;
          8. Any other co-morbidity which, in the opinion of the investigator, may affect patient&#xD;
             participation in the clinical trial.&#xD;
&#xD;
          9. Patients allergic to/intolerant of any components of the study treatment.&#xD;
&#xD;
         10. Patients with hereditary lactose intolerance.&#xD;
&#xD;
         11. Malabsorption syndrome, including congenital or acquired lactase deficiency (or any&#xD;
             other disaccharidase deficiency) and galactosemia.&#xD;
&#xD;
         12. Pregnancy, breast-feeding or unwillingness to use birth control during the study.&#xD;
&#xD;
         13. Patients who, from the investigator's point of view, will not comply with the&#xD;
             observation requirements of the study or adhere to study drug dosing regimens.&#xD;
&#xD;
         14. Patients with a history of non-adherence to medication; mental disorder (except for&#xD;
             cognitive deficits); or alcoholism or abuse of psychoactive substances, which, in the&#xD;
             investigator's opinion, will compromise compliance with study procedures.&#xD;
&#xD;
         15. Patients who have used medications listed in 'Prohibited Concomitant Treatment' in the&#xD;
             past week.&#xD;
&#xD;
         16. Participation in other clinical trials in the previous 3 months.&#xD;
&#xD;
         17. Patients who are related to any of the on-site research personnel directly involved in&#xD;
             the conduct of the trial or are an immediate relative of the study investigator.&#xD;
             'Immediate relative' means husband, wife, parent, son, daughter, brother, or sister&#xD;
             (regardless of whether they are natural or adopted).&#xD;
&#xD;
         18. Patients who work for MATERIA MEDICA HOLDING (i.e. the company's employees, temporary&#xD;
             contract workers, appointed officials responsible for carrying out the research or&#xD;
             immediate relatives of the aforementioned).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Arkhangelsk Regional Clinical Hospital</name>
      <address>
        <city>Arkhangel'sk</city>
        <zip>163045</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Belgorod Regional Clinical Hospital of St. Joseph</name>
      <address>
        <city>Belgorod</city>
        <zip>308007</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Non-State Healthcare Institution &quot;Divisional Hospital at the Bryansk-2 station of the open joint-stock company Russian Railways&quot;</name>
      <address>
        <city>Bryansk</city>
        <zip>241004</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bryansk Regional Hospital № 1</name>
      <address>
        <city>Bryansk</city>
        <zip>241033</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>Scientific-Research Institute - Regional Clinical Hospital №1 named after Professor S.V. Ochapovsky</name>
      <address>
        <city>Krasnodar</city>
        <zip>350086</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>State Budgetary Institution of Healthcare of the City of Moscow City Clinical Hospital No. 1 named after. N.I. Pirogov Moscow Department of Health</name>
      <address>
        <city>Moscow</city>
        <zip>119049</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City Clinical Hospital named after SI. Spasokokukotsky Department of Health of Moscow</name>
      <address>
        <city>Moscow</city>
        <zip>127206</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City Clinical Hospital №5 of Nizhny Novgorod region of Nizhny Novgorod</name>
      <address>
        <city>Nizhny Novgorod</city>
        <zip>603005</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Privolzhskiy Research Medical University</name>
      <address>
        <city>Nizhny Novgorod</city>
        <zip>603005</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>Pyatigorsk City Clinical Hospital № 2</name>
      <address>
        <city>Pyatigorsk</city>
        <zip>357538</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ryazan State Medical University named after academician I.P. Pavlov</name>
      <address>
        <city>Ryazan'</city>
        <zip>390026</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Petersburg I. I. Dzhanelidze Research Institute of Emergency Medicine</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>192242</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Leningrad Regional Clinical Hospital</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>194291</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State budgetary institution of health care of the Samara region &quot;Samara City Clinical Hospital № 1 named after NI Pirogov&quot;</name>
      <address>
        <city>Samara</city>
        <zip>443096</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Republican Clinical Hospital №4</name>
      <address>
        <city>Saransk</city>
        <zip>430032</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>St. Petersburg State Budgetary Institution &quot;City Hospital No. 40 in the Kurortny District&quot;</name>
      <address>
        <city>Sestroretsk</city>
        <zip>197706</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Smolensk State Medical University</name>
      <address>
        <city>Smolensk</city>
        <zip>214018</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State budgetary institution of health care of the Tver region &quot;Regional Clinical Treatment and Rehabilitation Center&quot;</name>
      <address>
        <city>Tver</city>
        <zip>170026</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Healthcare Institution Ulyanovsk Regional Clinical Hospital</name>
      <address>
        <city>Ulyanovsk</city>
        <zip>432063</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>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>Voronezh Regional Clinical Hospital № 1</name>
      <address>
        <city>Voronezh</city>
        <zip>394066</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vsevolozhsk Clinical Interdistrict Hospital</name>
      <address>
        <city>Vsevolozhsk</city>
        <zip>188643</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>Russian Federation</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>November 11, 2018</study_first_submitted>
  <study_first_submitted_qc>January 23, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 24, 2019</study_first_posted>
  <results_first_submitted>December 17, 2020</results_first_submitted>
  <results_first_submitted_qc>February 5, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">February 23, 2021</results_first_posted>
  <last_update_submitted>February 5, 2021</last_update_submitted>
  <last_update_submitted_qc>February 5, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 23, 2021</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>Stroke</mesh_term>
    <mesh_term>Ischemic Stroke</mesh_term>
    <mesh_term>Cerebral Infarction</mesh_term>
    <mesh_term>Ischemia</mesh_term>
    <mesh_term>Cognitive Dysfunction</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>August 29, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/92/NCT03815292/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>In total, 276 patients signed informed consent. After screening procedures, data from 1 patient did not meet the inclusion / exclusion criteria. The study randomized 275 patients.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>MMH-MAP</title>
          <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in mouth without chewing until complete dissolution. The duration of treatment will be 24 weeks.&#xD;
MMH-MAP: Oral administration</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo for 24 weeks, according to the MMH-MAP dosing regimen.&#xD;
Placebo: Oral administration</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="135"/>
                <participants group_id="P2" count="140"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="135"/>
                <participants group_id="P2" count="140"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>MMH-MAP</title>
          <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in mouth without chewing until complete dissolution. The duration of treatment will be 24 weeks.&#xD;
MMH-MAP: Oral administration</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo for 24 weeks, according to the MMH-MAP dosing regimen.&#xD;
Placebo: Oral administration</description>
        </group>
        <group group_id="B3">
          <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="135"/>
            <count group_id="B2" value="140"/>
            <count group_id="B3" value="275"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <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="135"/>
                    <count group_id="B2" value="140"/>
                    <count group_id="B3" value="275"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="64.5" spread="7.7"/>
                    <measurement group_id="B2" value="63.5" spread="8.5"/>
                    <measurement group_id="B3" value="64.0" spread="8.1"/>
                  </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="135"/>
                    <count group_id="B2" value="140"/>
                    <count group_id="B3" value="275"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="62"/>
                    <measurement group_id="B2" value="62"/>
                    <measurement group_id="B3" value="124"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="73"/>
                    <measurement group_id="B2" value="78"/>
                    <measurement group_id="B3" value="151"/>
                  </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_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" 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>Russia</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="135"/>
                    <count group_id="B2" value="140"/>
                    <count group_id="B3" value="275"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="135"/>
                    <measurement group_id="B2" value="140"/>
                    <measurement group_id="B3" value="275"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Patients With Improved Cognitive Function (The Montreal Cognitive Assessment Test Total Score of the Baseline +1 or More)</title>
        <description>MoCa is the test for assessment of cognitive impairment. The score ranges between 0 and 30. A score of 26-30 is normal. A score less than 26 is considered as mild cognitive impairment. Higher values represent a better outcome.</description>
        <time_frame>24 weeks of the treatment as compared to the baseline</time_frame>
        <group_list>
          <group group_id="O1">
            <title>MMH-MAP</title>
            <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in mouth without chewing until complete dissolution. The duration of treatment will be 24 weeks.&#xD;
MMH-MAP: Oral administration</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo for 24 weeks, according to the MMH-MAP dosing regimen.&#xD;
Placebo: Oral administration</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients With Improved Cognitive Function (The Montreal Cognitive Assessment Test Total Score of the Baseline +1 or More)</title>
          <description>MoCa is the test for assessment of cognitive impairment. The score ranges between 0 and 30. A score of 26-30 is normal. A score less than 26 is considered as mild cognitive impairment. Higher values represent a better outcome.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="135"/>
                <count group_id="O2" value="140"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="124"/>
                    <measurement group_id="O2" value="115"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.02</p_value>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in MoCA (The Montreal Cognitive Assessment Test) Score</title>
        <description>MoCa is the test for assessment of cognitive impairment. The score ranges between 0 and 30. A score of 26-30 is normal. A score less than 26 is considered as mild cognitive impairment. Higher values represent a better outcome.</description>
        <time_frame>24 weeks of the treatment as compared to the baseline</time_frame>
        <group_list>
          <group group_id="O1">
            <title>MMH-MAP</title>
            <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in mouth without chewing until complete dissolution. The duration of treatment will be 24 weeks.&#xD;
MMH-MAP: Oral administration</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo for 24 weeks, according to the MMH-MAP dosing regimen.&#xD;
Placebo: Oral administration</description>
          </group>
        </group_list>
        <measure>
          <title>Change in MoCA (The Montreal Cognitive Assessment Test) Score</title>
          <description>MoCa is the test for assessment of cognitive impairment. The score ranges between 0 and 30. A score of 26-30 is normal. A score less than 26 is considered as mild cognitive impairment. Higher values represent a better outcome.</description>
          <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="135"/>
                <count group_id="O2" value="140"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.4" spread="2.3"/>
                    <measurement group_id="O2" value="19.2" spread="2.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After 24 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.3" spread="2.7"/>
                    <measurement group_id="O2" value="22.5" spread="3.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>∆ between baseline and after 24 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.8" spread="2.4"/>
                    <measurement group_id="O2" value="3.1" spread="2.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>This analysis applies to ∆ between baseline and after 24 weeks total scores row.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0445</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Percentage of Patients With Improved Performance in Activities of Daily Living (Barthel Index Score of the Baseline + 5 or More)</title>
        <description>Scale for measurement of performance in activities of daily living (ADL).The maximum score is 100. A score of 91-99 stands for mild dependence in ADL performance, 61-90 - for moderate dependence in ADL performance, 21-60 - for severe dependence in ADL performance, 0-20 - for complete dependence in ADL performance. Higher values represent a better outcome.</description>
        <time_frame>24 weeks of the treatment as compared to the baseline</time_frame>
        <population>According to this criterion, data were obtained for 131 patients of the MMH-MAP group and 127 patients of the Placebo group.</population>
        <group_list>
          <group group_id="O1">
            <title>MMH-MAP</title>
            <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in mouth without chewing until complete dissolution. The duration of treatment will be 24 weeks.&#xD;
MMH-MAP: Oral administration</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo for 24 weeks, according to the MMH-MAP dosing regimen.&#xD;
Placebo: Oral administration</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients With Improved Performance in Activities of Daily Living (Barthel Index Score of the Baseline + 5 or More)</title>
          <description>Scale for measurement of performance in activities of daily living (ADL).The maximum score is 100. A score of 91-99 stands for mild dependence in ADL performance, 61-90 - for moderate dependence in ADL performance, 21-60 - for severe dependence in ADL performance, 0-20 - for complete dependence in ADL performance. Higher values represent a better outcome.</description>
          <population>According to this criterion, data were obtained for 131 patients of the MMH-MAP group and 127 patients of the Placebo group.</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="131"/>
                <count group_id="O2" value="127"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="118"/>
                    <measurement group_id="O2" value="102"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0345</p_value>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Barthel Index Score</title>
        <description>Scale for measurement of performance in activities of daily living (ADL).The maximum score is 100. A score of 91-99 stands for mild dependence in ADL performance, 61-90 - for moderate dependence in ADL performance, 21-60 - for severe dependence in ADL performance, 0-20 - for complete dependence in ADL performance. Higher values represent a better outcome.</description>
        <time_frame>24 weeks of the treatment as compared to the baseline</time_frame>
        <group_list>
          <group group_id="O1">
            <title>MMH-MAP</title>
            <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in mouth without chewing until complete dissolution. The duration of treatment will be 24 weeks.&#xD;
MMH-MAP: Oral administration</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo for 24 weeks, according to the MMH-MAP dosing regimen.&#xD;
Placebo: Oral administration</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Barthel Index Score</title>
          <description>Scale for measurement of performance in activities of daily living (ADL).The maximum score is 100. A score of 91-99 stands for mild dependence in ADL performance, 61-90 - for moderate dependence in ADL performance, 21-60 - for severe dependence in ADL performance, 0-20 - for complete dependence in ADL performance. Higher values represent a better outcome.</description>
          <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="135"/>
                <count group_id="O2" value="140"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="74.7" spread="5.4"/>
                    <measurement group_id="O2" value="74.8" spread="5.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After 24 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="89.7" spread="8.7"/>
                    <measurement group_id="O2" value="86.6" spread="11.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>∆ between baseline and after 24 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.9" spread="8.8"/>
                    <measurement group_id="O2" value="12.2" spread="10.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>This analysis applies to ∆ between baseline and after 24 weeks total scores row.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.04</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in SS-QOL (Stroke Specific Quality of Life Scale) Total Score</title>
        <description>Scale for assessment of health-related quality of life. The scale consists of 49 items in the 12 domains. Each domain consists of 3 to 10 items that are averaged to generate an overall score. Total score minimum value is 1 and maximum value is 245. Higher values represent a better outcome.</description>
        <time_frame>24 weeks of the treatment as compared to the baseline</time_frame>
        <group_list>
          <group group_id="O1">
            <title>MMH-MAP</title>
            <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in mouth without chewing until complete dissolution. The duration of treatment will be 24 weeks.&#xD;
MMH-MAP: Oral administration</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo for 24 weeks, according to the MMH-MAP dosing regimen.&#xD;
Placebo: Oral administration</description>
          </group>
        </group_list>
        <measure>
          <title>Change in SS-QOL (Stroke Specific Quality of Life Scale) Total Score</title>
          <description>Scale for assessment of health-related quality of life. The scale consists of 49 items in the 12 domains. Each domain consists of 3 to 10 items that are averaged to generate an overall score. Total score minimum value is 1 and maximum value is 245. Higher values represent a better outcome.</description>
          <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="135"/>
                <count group_id="O2" value="140"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="155.6" spread="33.0"/>
                    <measurement group_id="O2" value="156.6" spread="32.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After 24 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="184.2" spread="35.3"/>
                    <measurement group_id="O2" value="173.7" spread="38.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>∆ between baseline and after 24 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.9" spread="26.1"/>
                    <measurement group_id="O2" value="17.5" spread="26.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>This analysis applies to ∆ between baseline and after 24 weeks total scores row.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0016</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>The CGI-EI (Clinical Global Impression Efficacy Index) Score</title>
        <description>Rating scale for assessment of the therapeutic effect of treatment and associated side effects. The scale consists of 2 items: therapeutic effect and side effects. Scores in therapeutic effect range from 1 (marked improvement) to 13 (unchanged or worse). Scores in side effects range from 0 (no side effects) to 3 (side effects outweigh therapeutic effects). Efficacy index ranges between 0 and 16. Higher values represent a worse result.</description>
        <time_frame>24 weeks of the treatment</time_frame>
        <population>According to this criterion, data were obtained for 131 patients of the MMH-MAP group and 127 patients of the Placebo group.</population>
        <group_list>
          <group group_id="O1">
            <title>MMH-MAP</title>
            <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in mouth without chewing until complete dissolution. The duration of treatment will be 24 weeks.&#xD;
MMH-MAP: Oral administration</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo for 24 weeks, according to the MMH-MAP dosing regimen.&#xD;
Placebo: Oral administration</description>
          </group>
        </group_list>
        <measure>
          <title>The CGI-EI (Clinical Global Impression Efficacy Index) Score</title>
          <description>Rating scale for assessment of the therapeutic effect of treatment and associated side effects. The scale consists of 2 items: therapeutic effect and side effects. Scores in therapeutic effect range from 1 (marked improvement) to 13 (unchanged or worse). Scores in side effects range from 0 (no side effects) to 3 (side effects outweigh therapeutic effects). Efficacy index ranges between 0 and 16. Higher values represent a worse result.</description>
          <population>According to this criterion, data were obtained for 131 patients of the MMH-MAP group and 127 patients of the Placebo group.</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="131"/>
                <count group_id="O2" value="127"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Therapeutic effect</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.7" spread="3.3"/>
                    <measurement group_id="O2" value="6.9" spread="3.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Side effects</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1" spread="0.4"/>
                    <measurement group_id="O2" value="0.1" spread="0.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Efficacy index</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.8" spread="3.4"/>
                    <measurement group_id="O2" value="7.0" spread="3.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>This analysis applies to Therapeutic effect row.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0054</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>This analysis applies to Side effects row.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.78</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>This analysis applies to Efficiency index row.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0042</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in MoCA (The Montreal Cognitive Assessment Test) Score During Follow-up</title>
        <description>Test for assessment of cognitive impairment. The score ranges between 0 and 30. A score of 26-30 is normal. A score less than 26 is considered as mild cognitive impairment. Higher values represent a better outcome.</description>
        <time_frame>24 and 28 weeks of the study</time_frame>
        <population>According to this criterion, data were obtained for 131 patients of the MMH-MAP group and 127 patients of the Placebo group.</population>
        <group_list>
          <group group_id="O1">
            <title>MMH-MAP</title>
            <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in mouth without chewing until complete dissolution. The duration of treatment will be 24 weeks.&#xD;
MMH-MAP: Oral administration</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo for 24 weeks, according to the MMH-MAP dosing regimen.&#xD;
Placebo: Oral administration</description>
          </group>
        </group_list>
        <measure>
          <title>Change in MoCA (The Montreal Cognitive Assessment Test) Score During Follow-up</title>
          <description>Test for assessment of cognitive impairment. The score ranges between 0 and 30. A score of 26-30 is normal. A score less than 26 is considered as mild cognitive impairment. Higher values represent a better outcome.</description>
          <population>According to this criterion, data were obtained for 131 patients of the MMH-MAP group and 127 patients of the Placebo group.</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="131"/>
                <count group_id="O2" value="127"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>After 24 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.3" spread="2.7"/>
                    <measurement group_id="O2" value="22.5" spread="3.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After 28 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.6" spread="3.1"/>
                    <measurement group_id="O2" value="22.7" spread="3.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>∆ between 24 and 28 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4" spread="1.3"/>
                    <measurement group_id="O2" value="0.3" spread="1.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>This analysis applies to ∆ between 24 and 28 weeks total scores row.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.77</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Barthel Index Score During Follow-up</title>
        <description>Scale for measurement of performance in activities of daily living (ADL). The maximum score is 100. A score of 91-99 stands for mild dependence in ADL performance, 61-90 - for moderate dependence in ADL performance, 21-60 - for severe dependence in ADL performance, 0-20 - for complete dependence in ADL performance. Higher values represent a better outcome.</description>
        <time_frame>24 and 28 weeks of the study</time_frame>
        <population>According to this criterion, data were obtained for 131 patients of the MMH-MAP group and 127 patients of the Placebo group.</population>
        <group_list>
          <group group_id="O1">
            <title>MMH-MAP</title>
            <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in mouth without chewing until complete dissolution. The duration of treatment will be 24 weeks.&#xD;
MMH-MAP: Oral administration</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo for 24 weeks, according to the MMH-MAP dosing regimen.&#xD;
Placebo: Oral administration</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Barthel Index Score During Follow-up</title>
          <description>Scale for measurement of performance in activities of daily living (ADL). The maximum score is 100. A score of 91-99 stands for mild dependence in ADL performance, 61-90 - for moderate dependence in ADL performance, 21-60 - for severe dependence in ADL performance, 0-20 - for complete dependence in ADL performance. Higher values represent a better outcome.</description>
          <population>According to this criterion, data were obtained for 131 patients of the MMH-MAP group and 127 patients of the Placebo group.</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="131"/>
                <count group_id="O2" value="127"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>After 24 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="89.7" spread="8.7"/>
                    <measurement group_id="O2" value="86.6" spread="11.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After 28 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="90.6" spread="10.9"/>
                    <measurement group_id="O2" value="87.4" spread="10.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>∆ between 24 and 28 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5" spread="3.1"/>
                    <measurement group_id="O2" value="0.6" spread="3.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>This analysis applies to ∆ between 24 and 28 weeks total scores row.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0118</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Total SS-QOL (Stroke Specific Quality of Life Scale) Score During Follow-up</title>
        <description>Scale for assessment of health-related quality of life. The scale consists of 49 items in the 12 domains.Each domain consists of 3 to 10 items that are averaged to generate an overall score.Total score minimum value is 1 and maximum value is 245.Higher values represent a better outcome.</description>
        <time_frame>24 and 28 weeks of the study</time_frame>
        <population>According to this criterion, data were obtained for 131 patients of the MMH-MAP group and 127 patients of the Placebo group.</population>
        <group_list>
          <group group_id="O1">
            <title>MMH-MAP</title>
            <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in mouth without chewing until complete dissolution. The duration of treatment will be 24 weeks.&#xD;
MMH-MAP: Oral administration</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo for 24 weeks, according to the MMH-MAP dosing regimen.&#xD;
Placebo: Oral administration</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Total SS-QOL (Stroke Specific Quality of Life Scale) Score During Follow-up</title>
          <description>Scale for assessment of health-related quality of life. The scale consists of 49 items in the 12 domains.Each domain consists of 3 to 10 items that are averaged to generate an overall score.Total score minimum value is 1 and maximum value is 245.Higher values represent a better outcome.</description>
          <population>According to this criterion, data were obtained for 131 patients of the MMH-MAP group and 127 patients of the Placebo group.</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="131"/>
                <count group_id="O2" value="127"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>After 24 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="184.2" spread="35.3"/>
                    <measurement group_id="O2" value="173.7" spread="38.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After 28 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="187.8" spread="37.7"/>
                    <measurement group_id="O2" value="174.7" spread="38.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>∆ between 24 and 28 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.1" spread="9.5"/>
                    <measurement group_id="O2" value="2.8" spread="10.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>This analysis applies to ∆ between 24 and 28 weeks total scores row.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.058</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>During the study - 28 weeks.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>MMH-MAP</title>
          <description>Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in mouth without chewing until complete dissolution. The duration of treatment will be 24 weeks.&#xD;
MMH-MAP: Oral administration</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo for 24 weeks, according to the MMH-MAP dosing regimen.&#xD;
Placebo: Oral administration</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <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="135"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="135"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <description>Acute abdomen</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Acute coronary syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nosocomial pneumonia</sub_title>
                <description>Early nosocomial right-sided mid-lobe pneumonia</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebral infarction</sub_title>
                <description>Recurrent cerebral infarction</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Vertebrobasilar stroke</sub_title>
                <description>Repeated ischemic stroke in the vertebrobasilar basin with infarction in the left cerebellar hemisphere</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Recurrent stroke</sub_title>
                <description>Recurrent cryptogenic ischemic stroke in the vertebrobasilar basin</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Limb vein thrombosis</sub_title>
                <description>Lower limb vein phlebothrombosis</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <description>Deep vein thrombosis of the right leg</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </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="37" subjects_at_risk="135"/>
                <counts group_id="E2" subjects_affected="39" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute coronary syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Heartbeat</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute abdomen</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Pain in the upper abdomen</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Hunger</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Gallbladder polyp</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Liver steatosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="135"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Oral herpes</sub_title>
                <description>Upper lip herpes</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Tonsillitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Hematoma due to trauma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Ligament sprain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Protein in urine</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Oxalates in urine</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Abnormal urine test results</sub_title>
                <description>Leukocyte esterase, hemoglobin traces, nitrites, leukocytes, erythrocytes, bacteria in a small amount</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Increased blood pressure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Increased liver enzyme levels</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Blood pressure decrease</sub_title>
                <description>Decrease in blood pressure on an outpatient basis</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Weight gain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Hypercholesterolemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Limb pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Periarthritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="135"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Cognitive impairment</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Memory disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Lumbar radiculopathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Cerebral infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Affective lability</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Increased libido</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Low mood</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Sense of anxiety</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Metrorrhagia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dysphonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Itchy rash</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Hypertensive crisis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Labile blood pressure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="135"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Limb vein thrombosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="135"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="140"/>
              </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/NCT03815292
org study id: MMH-MAP-001
nct id: NCT03815292
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is:

        -  to evaluate efficacy of MMH-MAP in the treatment of mild cognitive impairment in
           subjects in early rehabilitation period of ischemic stroke

        -  to evaluate safety of MMH-MAP in the treatment of mild cognitive impairment in subjects
           in early rehabilitation period of ischemic stroke
A double-blind, placebo-controlled randomized clinical trial in parallel groups.

      The study patients are subjects of either gender, aged 45-80 years old, after an ischemic
      stroke within 3-6 months prior to enrollment and confirmed by neuroimaging, having mild
      cognitive impairment.

      After the patients provide signed Participant Information Sheet and Informed Consent, they
      will be interviewed for complaints and medical history and undergo physical examination and
      laboratory tests. The doctor will rate the severity of patients' cognitive impairments on the
      Mini Mental State Examination (MMSE) scale and Montreal Cognitive Assessment (MoCA) scale,
      assess their performance in activities of daily living on the Barthel Index scale [Collin C,
      Wade DT, Davies S, Horne V. "The Barthel ADL Index: a reliability study." Int Disability
      Study.1988;10:61-63.], and administer the Stroke Specific Quality of Life Scale (SS-QOL)
      questionnaire [Williams LS, Weinberger M, Harris LE, Clark DO, Biller J. Development of a
      stroke-specific quality of life scale. Stroke 1999 Jul;30(7):1362-9]. Eligible participants
      will have to have moderate cognitive impairments (MMSE score - at least 21 and MoCA - less
      than 26). Therapy received by patients for their co-morbidities and primary diagnosis will be
      recorded. All women of childbearing potential will be administered pregnancy tests.

      If a patient meets all inclusion criteria and does not have any exclusion criteria at Visit
      1, he/she is randomized to one of the two groups: group 1 will receive MMH-MAP at 2 tablets
      twice daily; group 2 will receive Placebo using the study product dosing regimen. The total
      duration of follow-up and treatment will be 28 weeks, which will include 5 additional visits.

      At Visit 2 (Week 4±7 days), the doctor records patients' complaints and physical examination
      data, reviews the progress of study and basic and concomitant therapy, and assesses treatment
      safety and patient compliance with treatment.

      At Visit 3 (Week 8±7 days), Visit 4 (Week 16±7 days), and Visit 5 (Week 24±7 days), the
      doctor assesses patients' cognitive impairments (MoCA) and performance in activities of daily
      living (the Barthel Index). The patients complete the SS-QOL questionnaire.

      At Visit 5 (Week 24±7 days), the doctor will additionally complete the Clinical Global
      Impression Efficacy Index (CGI-EI) scale [Guy W, editor. ECDEU Assessment Manual for
      Psychopharmacology. 1976 Rockville, MD, U.S. Department of Health, Education, and Welfare]
      and collect samples for laboratory testing. The patient stops taking the study drug.

      After four weeks following the end of study therapy patients complete a follow-up visit
      -Visit 6 (Week 28±7 days). The patients are interviewed for complaints and undergo physical
      examination, with a check on their concomitant and primary therapies as well as on the safety
      of study treatment. The doctor assesses patients' cognitive impairments (MoCA) and
      performance in activities of daily living (the Barthel Index) and administers the SS-QOL
      questionnaire.

      The total length of the observation period will be 28 weeks. During the study, symptomatic
      therapy and therapy for underlying chronic conditions are allowed with the exception of the
      drugs indicated in the section "Prohibited Concomitant Treatment".
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Percentage of Patients With Improved Cognitive Function (The Montreal Cognitive Assessment Test Total Score of the Baseline +1 or More)
time frame: 24 weeks of the treatment as compared to the baseline
description: MoCa is the test for assessment of cognitive impairment. The score ranges between 0 and 30. A score of 26-30 is normal. A score less than 26 is considered as mild cognitive impairment. Higher values represent a better outcome.
measure: Change in MoCA (The Montreal Cognitive Assessment Test) Score
time frame: 24 weeks of the treatment as compared to the baseline
description: MoCa is the test for assessment of cognitive impairment. The score ranges between 0 and 30. A score of 26-30 is normal. A score less than 26 is considered as mild cognitive impairment. Higher values represent a better outcome.
measure: Percentage of Patients With Improved Performance in Activities of Daily Living (Barthel Index Score of the Baseline + 5 or More)
time frame: 24 weeks of the treatment as compared to the baseline
description: Scale for measurement of performance in activities of daily living (ADL).The maximum score is 100. A score of 91-99 stands for mild dependence in ADL performance, 61-90 - for moderate dependence in ADL performance, 21-60 - for severe dependence in ADL performance, 0-20 - for complete dependence in ADL performance. Higher values represent a better outcome.
measure: Change in Barthel Index Score
time frame: 24 weeks of the treatment as compared to the baseline
description: Scale for measurement of performance in activities of daily living (ADL).The maximum score is 100. A score of 91-99 stands for mild dependence in ADL performance, 61-90 - for moderate dependence in ADL performance, 21-60 - for severe dependence in ADL performance, 0-20 - for complete dependence in ADL performance. Higher values represent a better outcome.
measure: Change in SS-QOL (Stroke Specific Quality of Life Scale) Total Score
time frame: 24 weeks of the treatment as compared to the baseline
description: Scale for assessment of health-related quality of life. The scale consists of 49 items in the 12 domains. Each domain consists of 3 to 10 items that are averaged to generate an overall score. Total score minimum value is 1 and maximum value is 245. Higher values represent a better outcome.
measure: The CGI-EI (Clinical Global Impression Efficacy Index) Score
time frame: 24 weeks of the treatment
description: Rating scale for assessment of the therapeutic effect of treatment and associated side effects. The scale consists of 2 items: therapeutic effect and side effects. Scores in therapeutic effect range from 1 (marked improvement) to 13 (unchanged or worse). Scores in side effects range from 0 (no side effects) to 3 (side effects outweigh therapeutic effects). Efficacy index ranges between 0 and 16. Higher values represent a worse result.
measure: Change in MoCA (The Montreal Cognitive Assessment Test) Score During Follow-up
time frame: 24 and 28 weeks of the study
description: Test for assessment of cognitive impairment. The score ranges between 0 and 30. A score of 26-30 is normal. A score less than 26 is considered as mild cognitive impairment. Higher values represent a better outcome.
measure: Change in Barthel Index Score During Follow-up
time frame: 24 and 28 weeks of the study
description: Scale for measurement of performance in activities of daily living (ADL). The maximum score is 100. A score of 91-99 stands for mild dependence in ADL performance, 61-90 - for moderate dependence in ADL performance, 21-60 - for severe dependence in ADL performance, 0-20 - for complete dependence in ADL performance. Higher values represent a better outcome.
measure: Change in Total SS-QOL (Stroke Specific Quality of Life Scale) Score During Follow-up
time frame: 24 and 28 weeks of the study
description: Scale for assessment of health-related quality of life. The scale consists of 49 items in the 12 domains.Each domain consists of 3 to 10 items that are averaged to generate an overall score.Total score minimum value is 1 and maximum value is 245.Higher values represent a better outcome.
arm group label: MMH-MAP
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 mouth without chewing until complete dissolution. The duration of treatment will be 24 weeks.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo for 24 weeks, according to the MMH-MAP dosing regimen.
intervention type: Drug
intervention name: MMH-MAP
description: Oral administration
arm group label: MMH-MAP
intervention type: Drug
intervention name: Placebo
description: Oral administration
arm group label: Placebo
criteria: 
gender: All
minimum age: 45 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
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country: Russian Federation
responsible party type: Sponsor
mesh term: Stroke
mesh term: Ischemic Stroke
mesh term: Cerebral Infarction
mesh term: Ischemia
mesh term: Cognitive Dysfunction
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 