<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/NCT01716104</url>
  </required_header>
  <id_info>
    <org_study_id>MMH-AZ-001-I</org_study_id>
    <nct_id>NCT01716104</nct_id>
  </id_info>
  <brief_title>Clinical Trial of Safety and Efficacy of Afalaza in Patients With Symptoms of Benign Prostatic Hyperplasia and Risk of Progression</brief_title>
  <official_title>Multicentric Double-blind Placebo-controlled Randomized Parallel-group Clinical Trial of Safety and Efficacy of Afalaza in Patients With Symptoms of Benign Prostatic Hyperplasia and Risk of Progression</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Materia Medica Holding</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Materia Medica Holding</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is:&#xD;
&#xD;
        -  To assess safety of Afalaza drug within 12 months in patients with symptoms of benign&#xD;
           prostatic hyperplasia (BPH) and risk of progression.&#xD;
&#xD;
        -  To assess efficacy of Afalaza drug within 12 months in patients with symptoms of benign&#xD;
           prostatic hyperplasia and risk of progression.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">November 2016</completion_date>
  <primary_completion_date type="Actual">November 2016</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>Change in Total IPSS Scores (International Prostate Symptome Score) After 1, 3, 6 and 12 Months Compared to Baseline.</measure>
    <time_frame>Baseline, 1, 3, 6 and 12 months</time_frame>
    <description>The International Prostate Symptom Score (IPSS) is based on the answers to 7 questions concerning urinary symptoms plus one question concerning quality of life (QoL). Each of the seven symptoms includes the assignment of scores from 0 to 5. The total score can therefore range from 0 to 35 points (asymptomatic to very symptomatic). The patient's quality of life (QoL) was evaluated separately in this clinical study.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Dynamics of Irritative Symptoms Evaluated by IPSS (International Prostate Symptome Score) After 1, 3, 6 and 12 Months Compared to Baseline</measure>
    <time_frame>Baseline and 1, 3, 6, 12 months</time_frame>
    <description>The International Prostate Symptom Score (IPSS) is based on the answers to 7 questions concerning urinary symptoms plus one question concerning quality of life (QoL). Each of the seven symptoms includes the assignment of scores from 0 to 5. The total score can therefore range from 0 to 35 points (asymptomatic to very symptomatic). The patient's quality of life (QoL) was evaluated separately in this clinical study.&#xD;
The sum of IPSS questions 2, 4, and 7 related to irritative symptoms. The total score of irritative symptoms can therefore range from 0 to 15 points (asymptomatic to very symptomatic).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Maximum Urinary Flow Rate After 1, 3, 6 and 12 Months Compared to Baseline</measure>
    <time_frame>Baseline and 1, 3, 6 and 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Average Urinary Flow Rate After 1, 3, 6 and 12 Months Compared to Baseline</measure>
    <time_frame>Baseline and 1, 3, 6 and 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change in Mean Values of Prostate Gland Volume at 3, 6 and 12 Months Compared to Baseline</measure>
    <time_frame>Baseline and 3, 6 and 12 months</time_frame>
    <description>Change in the volume of the prostate gland as a percentage of the baseline according to transrectal ultrasound</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Mean Values of Micturition Volume at 3, 6 and 12 Months Compared to Baseline</measure>
    <time_frame>Baseline and 3, 6 and 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the Mean Values of Residual Urine Volume at 3, 6 and 12 Months Compared to Baseline</measure>
    <time_frame>Baseline and 3, 6 and 12 months</time_frame>
    <description>according to transabdominal ultrasound</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Quality of Life (QoL Index of IPSS) at 3, 6 and 12 Months Compared to Baseline</measure>
    <time_frame>Baseline and 3, 6 and 12 months</time_frame>
    <description>Quality of life (QoL) Due to Urinary Symptoms is an eight point of the IPSS scale referred to the patient's quality of life. The answers to this question range from &quot;delighted&quot; to &quot;terrible&quot; or 0 to 5.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Total Value of Risk Factors for Progression (Total Score of IPSS, Prostate Volume, PSA Level, Maximum Urinary Flow Rate, Residual Urine Volume) Compared to Baseline</measure>
    <time_frame>Baseline and 3, 6 and 12 months</time_frame>
    <description>To assess the risk of BPH progression, the following were used: 1) moderate to severe BPH symptoms (ie, IPSS total score&gt; 7); 2) an increase in the volume of the prostate gland (&gt; 30 cm^2); 3) increased PSA level in the blood (≥ 1.4 ng / ml); 4) a decrease in Qmax (&lt;12 ml / s) and 5) a large volume of residual urine (&gt; 200 ml).&#xD;
The total value of risk factors for progression is assessed as the sum of the risk factors that the patient had at the time of inclusion in the study (presence of risk factors = 1 point, absence = 0 points). After 3, 6 and 12 months of treatment, the dynamics of risk factors for progression was assessed: an increase in the severity of the risk factor meant +1, no change = 0, a decrease in the severity of the risk factor of -1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Episodes of Acute Urinary Retention, Surgical Intervention During the Observation Period</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">260</enrollment>
  <condition>Benign Prostatic Hyperplasia</condition>
  <arm_group>
    <arm_group_label>Afalaza (2 tablets twice a day)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo (2 tablets twice a day)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Afalaza</intervention_name>
    <description>Safety and Efficacy</description>
    <arm_group_label>Afalaza (2 tablets twice a day)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Safety and Efficacy</description>
    <arm_group_label>Placebo (2 tablets twice a day)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male patients 45 to 60 y.o. inclusive with a documented diagnosis of Benign prostatic&#xD;
             hyperplasia.&#xD;
&#xD;
          2. Lower urinary tract symptoms (LUTS) having been experienced for 3 months and longer.&#xD;
&#xD;
          3. Total IPSS score (International Prostate Symptome Score) of 8 to 15.&#xD;
&#xD;
          4. Prostate volume of more than 30 cm3.&#xD;
&#xD;
          5. Maximal urinary flow rate of 10-15 mL/sec.&#xD;
&#xD;
          6. Micturition volume of 125-350 mL.&#xD;
&#xD;
          7. Residual volume of less than 100 mL.&#xD;
&#xD;
          8. Serum prostate-specific antigen (PSA) level of less than 4 ng/mL.&#xD;
&#xD;
          9. Use of and compliance with contraceptive methods during the trial and for 30 days upon&#xD;
             completion of participation in the trial.&#xD;
&#xD;
         10. Presence of the patient's information sheet (informed consent form) for participation&#xD;
             in the clinical trial.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Invasive therapies for BPH including a transurethral prostatic resection,&#xD;
             thermotherapy, microwave therapy, transurethral needle ablation, stenting, etc.&#xD;
&#xD;
          2. Malignant oncological disease of the urogenital system as well as malignancies of any&#xD;
             other localization during last 5 years.&#xD;
&#xD;
          3. Acute urinary retention (AUR) within 3 months before inclusion in the trial.&#xD;
&#xD;
          4. Neurogenic dysfunctions and bladder ears.&#xD;
&#xD;
          5. Urinary stone disease.&#xD;
&#xD;
          6. Urethral stricture, bladder neck sclerosis.&#xD;
&#xD;
          7. History of operative aids for pelvic organs.&#xD;
&#xD;
          8. Urogenital infections in the phase of active inflammation.&#xD;
&#xD;
          9. Systematic administration of agents exhibiting effects on bladder function and urine&#xD;
             production.&#xD;
&#xD;
         10. Exacerbation or decompensation of chronic diseases affecting the possibility of&#xD;
             patients to participate in the clinical trial, including severe concurrent&#xD;
             cardiovascular conditions and disorders of the nervous system, renal and hepatic&#xD;
             insufficiency.&#xD;
&#xD;
         11. History of administration of testosterone 5-alpha-reductase inhibitors (finasteride,&#xD;
             dutasteride).&#xD;
&#xD;
         12. History of polyvalent allergy.&#xD;
&#xD;
         13. Allergy/intolerance to any component of drug agents used in the therapy.&#xD;
&#xD;
         14. Malabsorption syndrome, including congenital or acquired lactase or other&#xD;
             disaccharidase deficiency.&#xD;
&#xD;
         15. Administration of drugs specified as &quot;Prohibited concomitant therapy&quot;, within 3 months&#xD;
             before enrollment.&#xD;
&#xD;
         16. Exacerbation or decompensation of chronic diseases affecting the possibility of&#xD;
             patients to participate in the clinical trial.&#xD;
&#xD;
         17. Drug and alcohol consumption (over 2 alc. units daily), mental diseases. Legal&#xD;
             incapacity or limited legal capacity.&#xD;
&#xD;
         18. Legal incapacitation or limited legal capacity.&#xD;
&#xD;
         19. Patients, who, in the investigator's opinion, will fail to observe the requirements&#xD;
             during the trial or adhere to the studied drug administration procedure.&#xD;
&#xD;
         20. Participation in other clinical trials within 3 months before enrolment in this trial.&#xD;
&#xD;
         21. Presence of other factors, complicating the patient's participation in the trial&#xD;
             (e.g., planned lengthy business and other trips).&#xD;
&#xD;
         22. A patient is a part of the center's research staff, taking a direct part in the trial,&#xD;
             or an immediate family member of the investigator. Immediate family members are&#xD;
             defined as spouses, parents, children or siblings, regardless of whether full blood or&#xD;
             adopted.&#xD;
&#xD;
         23. The patient is employed with Scientific Production Firm Materia Medica Holding LLC,&#xD;
             i.e. is the company's employee, part-time employee under contract, or appointed&#xD;
             official in charge of the trial, or their immediate family.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Limited liability company &quot;Family Policlinic No. 4&quot;</name>
      <address>
        <city>Moscow region Koroljov</city>
        <zip>141060</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The State Budget Health Care institution of Moscow the City &quot;Hospital for veterans of wars No. 2 of the Administration of Health Care of Moscow City&quot;</name>
      <address>
        <city>Moscow</city>
        <zip>109472</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The State Budget Health Care institution of Moscow the City &quot;Specialized clinical (neuro-psychiatric) hospital No. 8 n.a. Z.P. Solovyov - ''Clinic of neuroses&quot; of the Administration of Health Care of Moscow City</name>
      <address>
        <city>Moscow</city>
        <zip>115419</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Federal State Budget Educational institution of High Professional Training &quot;Peoples' Friendship University of Russia&quot;, Department of Urology and Operative Nephrology</name>
      <address>
        <city>Moscow</city>
        <zip>117198</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The State Budget Educational institution of High Professional Training I.M. Sechenov First Moscow State Medical University of Ministry of Health Care and Social Development of the Russian Federation, Department of Urology</name>
      <address>
        <city>Moscow</city>
        <zip>119991</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The State Budgetary Educational Institution of Higher Professional Education &quot; Moscow State University of Medicine and Dentistry of A. I. Evdokimov&quot; Ministry of Health of the Russian Federation</name>
      <address>
        <city>Moscow</city>
        <zip>127473</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Federal State Budget institution &quot;Polyclinic № 3&quot; of Affairs Management Department of the President of the Russian Federation</name>
      <address>
        <city>Moscow</city>
        <zip>129090</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Municipal Treatment-and-Prophylactic Health Care institution Clinical Diagnostic Centre &quot;Zdorovie&quot;</name>
      <address>
        <city>Rostov-on-Don</city>
        <zip>344011</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Federal State Budgetary Institution &quot; Saint-Petersburg Research Institute Phthisiopulmonology &quot; Ministry of Health of the Russian Federation</name>
      <address>
        <city>St. Petersburg</city>
        <zip>191036</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Federal State institution &quot;All-Russian center of emergency and radiation medicine n.a. A.M. Nikiforov&quot; of the Ministry of the Russian Federation for Affairs of civil defence, emergencies and elimination of consequences of natural disasters</name>
      <address>
        <city>St. Petersburg</city>
        <zip>194044</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Federal State Budgetary Health Care Institution &quot;Clinical Hospital №122 n. a. L. G. Sokolov of the Federal Biomedical Agency&quot;</name>
      <address>
        <city>St. Petersburg</city>
        <zip>194291</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Limited liability company &quot;Medical unit No. 157&quot;</name>
      <address>
        <city>St. Petersburg</city>
        <zip>196066</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint-Petersburg State Budget Health Care institution &quot;Pokrovsky city hospital&quot;</name>
      <address>
        <city>St. Petersburg</city>
        <zip>199106</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Limited Liability Company &quot;Hospital OrCli&quot;</name>
      <address>
        <city>St. Petersburg</city>
        <zip>199178</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The State Budgetary Educational Institution of Higher Professional Education &quot; Siberian state Medical University&quot; Ministry of Health of the Russian Federation</name>
      <address>
        <city>Tomsk</city>
        <zip>634050</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The State Institution &quot;Institute of Urology of the Ukraine National Academy of Medical Sciences&quot;</name>
      <address>
        <city>Kyiv</city>
        <zip>04053</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Russian Federation</country>
    <country>Ukraine</country>
  </location_countries>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>October 25, 2012</study_first_submitted>
  <study_first_submitted_qc>October 25, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 29, 2012</study_first_posted>
  <results_first_submitted>July 17, 2017</results_first_submitted>
  <results_first_submitted_qc>December 18, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">October 9, 2018</results_first_posted>
  <last_update_submitted>November 1, 2018</last_update_submitted>
  <last_update_submitted_qc>November 1, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 28, 2018</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>Prostatic Hyperplasia</mesh_term>
    <mesh_term>Hyperplasia</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Selection procedures were carried out after participant enrollment to determine whether the patient could participate in the study in accordance with the inclusion criteria.&#xD;
Of the 260 patients enrolled, 11 did not meet inclusion criteria after screening procedures, they were not randomized.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Afalaza</title>
          <description>Afalaza (2 tablets twice a day) One tablet contains: affinity purified antibodies to endothelial nitric oxide synthase - 0.006g*, affinity purified antibodies to prostate-specific antigen - 0.006g*.&#xD;
*applied onto isomalt crystals as a mixture of three active aqueous-alcoholic dilutions of the drug substance - diluted 100^12, 100^30, 100^50 times, respectively.&#xD;
Excipients: lactose monohydrate; microcrystalline cellulose; magnesium stearate.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo (2 tablets twice a day)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="125"/>
                <participants group_id="P2" count="124"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="119"/>
                <participants group_id="P2" count="117"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Do not meet inclusion criteria</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Intention to treat set</population>
      <group_list>
        <group group_id="B1">
          <title>Afalaza</title>
          <description>Afalaza (2 tablets twice a day): Safety and Efficiency</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo (2 tablets twice a day): Safety and Efficiency</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="119"/>
            <count group_id="B2" value="117"/>
            <count group_id="B3" value="236"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="54.3" spread="4.2"/>
                    <measurement group_id="B2" value="54.4" spread="4.4"/>
                    <measurement group_id="B3" value="54.4" spread="4.3"/>
                  </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>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="119"/>
                    <measurement group_id="B2" value="117"/>
                    <measurement group_id="B3" value="236"/>
                  </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>Ukraine</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Russia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="118"/>
                    <measurement group_id="B2" value="114"/>
                    <measurement group_id="B3" value="232"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Total IPSS Scores (International Prostate Symptome Score) After 1, 3, 6 and 12 Months Compared to Baseline.</title>
        <description>The International Prostate Symptom Score (IPSS) is based on the answers to 7 questions concerning urinary symptoms plus one question concerning quality of life (QoL). Each of the seven symptoms includes the assignment of scores from 0 to 5. The total score can therefore range from 0 to 35 points (asymptomatic to very symptomatic). The patient's quality of life (QoL) was evaluated separately in this clinical study.</description>
        <time_frame>Baseline, 1, 3, 6 and 12 months</time_frame>
        <population>ITT set</population>
        <group_list>
          <group group_id="O1">
            <title>Afalaza</title>
            <description>Afalaza (2 tablets twice a day): Safety and Efficacy</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo (2 tablets twice a day): Safety and Efficacy</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Total IPSS Scores (International Prostate Symptome Score) After 1, 3, 6 and 12 Months Compared to Baseline.</title>
          <description>The International Prostate Symptom Score (IPSS) is based on the answers to 7 questions concerning urinary symptoms plus one question concerning quality of life (QoL). Each of the seven symptoms includes the assignment of scores from 0 to 5. The total score can therefore range from 0 to 35 points (asymptomatic to very symptomatic). The patient's quality of life (QoL) was evaluated separately in this clinical study.</description>
          <population>ITT set</population>
          <units>Scores 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="119"/>
                <count group_id="O2" value="117"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Month 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.3" spread="1.7"/>
                    <measurement group_id="O2" value="-0.6" spread="1.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.3" spread="2.1"/>
                    <measurement group_id="O2" value="-1.5" spread="1.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.0" spread="2.5"/>
                    <measurement group_id="O2" value="-1.9" spread="2.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.7" spread="3.0"/>
                    <measurement group_id="O2" value="-2.9" spread="2.4"/>
                  </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>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0005</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Dynamics of Irritative Symptoms Evaluated by IPSS (International Prostate Symptome Score) After 1, 3, 6 and 12 Months Compared to Baseline</title>
        <description>The International Prostate Symptom Score (IPSS) is based on the answers to 7 questions concerning urinary symptoms plus one question concerning quality of life (QoL). Each of the seven symptoms includes the assignment of scores from 0 to 5. The total score can therefore range from 0 to 35 points (asymptomatic to very symptomatic). The patient's quality of life (QoL) was evaluated separately in this clinical study.&#xD;
The sum of IPSS questions 2, 4, and 7 related to irritative symptoms. The total score of irritative symptoms can therefore range from 0 to 15 points (asymptomatic to very symptomatic).</description>
        <time_frame>Baseline and 1, 3, 6, 12 months</time_frame>
        <population>ITT set</population>
        <group_list>
          <group group_id="O1">
            <title>Afalaza</title>
            <description>Afalaza (2 tablets twice a day): Safety and Efficacy</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo (2 tablets twice a day): Safety and Efficacy</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Dynamics of Irritative Symptoms Evaluated by IPSS (International Prostate Symptome Score) After 1, 3, 6 and 12 Months Compared to Baseline</title>
          <description>The International Prostate Symptom Score (IPSS) is based on the answers to 7 questions concerning urinary symptoms plus one question concerning quality of life (QoL). Each of the seven symptoms includes the assignment of scores from 0 to 5. The total score can therefore range from 0 to 35 points (asymptomatic to very symptomatic). The patient's quality of life (QoL) was evaluated separately in this clinical study.&#xD;
The sum of IPSS questions 2, 4, and 7 related to irritative symptoms. The total score of irritative symptoms can therefore range from 0 to 15 points (asymptomatic to very symptomatic).</description>
          <population>ITT set</population>
          <units>Scores 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="119"/>
                <count group_id="O2" value="117"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Month 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.5" spread="0.9"/>
                    <measurement group_id="O2" value="-0.3" spread="1.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.9" spread="1.2"/>
                    <measurement group_id="O2" value="-0.6" spread="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.3" spread="1.5"/>
                    <measurement group_id="O2" value="-0.8" spread="1.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.5" spread="1.6"/>
                    <measurement group_id="O2" value="-1.3" spread="1.5"/>
                  </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>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.035</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Maximum Urinary Flow Rate After 1, 3, 6 and 12 Months Compared to Baseline</title>
        <time_frame>Baseline and 1, 3, 6 and 12 months</time_frame>
        <population>ITT set</population>
        <group_list>
          <group group_id="O1">
            <title>Afalaza</title>
            <description>Afalaza (2 tablets twice a day): Safety and Efficacy</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo (2 tablets twice a day): Safety and Efficacy</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Maximum Urinary Flow Rate After 1, 3, 6 and 12 Months Compared to Baseline</title>
          <population>ITT set</population>
          <units>ml/s</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="119"/>
                <count group_id="O2" value="117"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Month 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.3" spread="3.2"/>
                    <measurement group_id="O2" value="0.2" spread="2.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5" spread="3.2"/>
                    <measurement group_id="O2" value="0.7" spread="3.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.7" spread="3.2"/>
                    <measurement group_id="O2" value="0.5" spread="2.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.5" spread="4.3"/>
                    <measurement group_id="O2" value="1.4" spread="3.3"/>
                  </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>0.0008</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Average Urinary Flow Rate After 1, 3, 6 and 12 Months Compared to Baseline</title>
        <time_frame>Baseline and 1, 3, 6 and 12 months</time_frame>
        <population>ITT set</population>
        <group_list>
          <group group_id="O1">
            <title>Afalaza</title>
            <description>Afalaza (2 tablets twice a day): Safety and Efficacy</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo (2 tablets twice a day): Safety and Efficacy</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Average Urinary Flow Rate After 1, 3, 6 and 12 Months Compared to Baseline</title>
          <population>ITT set</population>
          <units>ml/s</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="119"/>
                <count group_id="O2" value="117"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Month 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.9" spread="2.0"/>
                    <measurement group_id="O2" value="0.2" spread="1.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.3" spread="2.1"/>
                    <measurement group_id="O2" value="0.7" spread="2.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.4" spread="2.0"/>
                    <measurement group_id="O2" value="0.5" spread="2.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.4" spread="2.2"/>
                    <measurement group_id="O2" value="0.6" spread="2.5"/>
                  </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>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0011</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change in Mean Values of Prostate Gland Volume at 3, 6 and 12 Months Compared to Baseline</title>
        <description>Change in the volume of the prostate gland as a percentage of the baseline according to transrectal ultrasound</description>
        <time_frame>Baseline and 3, 6 and 12 months</time_frame>
        <population>ITT set</population>
        <group_list>
          <group group_id="O1">
            <title>Afalaza</title>
            <description>Afalaza (2 tablets twice a day): Safety and Efficacy</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo (2 tablets twice a day): Safety and Efficacy</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in Mean Values of Prostate Gland Volume at 3, 6 and 12 Months Compared to Baseline</title>
          <description>Change in the volume of the prostate gland as a percentage of the baseline according to transrectal ultrasound</description>
          <population>ITT set</population>
          <units>percentage of prostate gland volume</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="119"/>
                <count group_id="O2" value="117"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Month 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.6" spread="13.1"/>
                    <measurement group_id="O2" value="-2.9" spread="12.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.0" spread="13.4"/>
                    <measurement group_id="O2" value="-4.9" spread="14.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-11.8" spread="16.0"/>
                    <measurement group_id="O2" value="-6.5" spread="14.7"/>
                  </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>0.0054</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Mean Values of Micturition Volume at 3, 6 and 12 Months Compared to Baseline</title>
        <time_frame>Baseline and 3, 6 and 12 months</time_frame>
        <population>ITT set</population>
        <group_list>
          <group group_id="O1">
            <title>Afalaza</title>
            <description>Afalaza (2 tablets twice a day): Safety and Efficacy</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo (2 tablets twice a day): Safety and Efficacy</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Mean Values of Micturition Volume at 3, 6 and 12 Months Compared to Baseline</title>
          <population>ITT set</population>
          <units>ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="119"/>
                <count group_id="O2" value="117"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Month 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.6" spread="105.0"/>
                    <measurement group_id="O2" value="1.4" spread="76.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.5" spread="96.6"/>
                    <measurement group_id="O2" value="5.0" spread="88.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.9" spread="106.0"/>
                    <measurement group_id="O2" value="0.4" spread="71.2"/>
                  </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>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0437</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in the Mean Values of Residual Urine Volume at 3, 6 and 12 Months Compared to Baseline</title>
        <description>according to transabdominal ultrasound</description>
        <time_frame>Baseline and 3, 6 and 12 months</time_frame>
        <population>ITT set</population>
        <group_list>
          <group group_id="O1">
            <title>Afalaza</title>
            <description>Afalaza (2 tablets twice a day): Safety and Efficacy</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo (2 tablets twice a day): Safety and Efficacy</description>
          </group>
        </group_list>
        <measure>
          <title>Change in the Mean Values of Residual Urine Volume at 3, 6 and 12 Months Compared to Baseline</title>
          <description>according to transabdominal ultrasound</description>
          <population>ITT set</population>
          <units>ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="119"/>
                <count group_id="O2" value="117"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Month 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.5" spread="26.5"/>
                    <measurement group_id="O2" value="-0.9" spread="21.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.8" spread="28.1"/>
                    <measurement group_id="O2" value="-4.3" spread="20.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.0" spread="30.1"/>
                    <measurement group_id="O2" value="-3.5" spread="26.9"/>
                  </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>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0862</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Quality of Life (QoL Index of IPSS) at 3, 6 and 12 Months Compared to Baseline</title>
        <description>Quality of life (QoL) Due to Urinary Symptoms is an eight point of the IPSS scale referred to the patient's quality of life. The answers to this question range from &quot;delighted&quot; to &quot;terrible&quot; or 0 to 5.</description>
        <time_frame>Baseline and 3, 6 and 12 months</time_frame>
        <population>ITT set</population>
        <group_list>
          <group group_id="O1">
            <title>Afalaza</title>
            <description>Afalaza (2 tablets twice a day): Safety and Efficacy</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo (2 tablets twice a day): Safety and Efficacy</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Quality of Life (QoL Index of IPSS) at 3, 6 and 12 Months Compared to Baseline</title>
          <description>Quality of life (QoL) Due to Urinary Symptoms is an eight point of the IPSS scale referred to the patient's quality of life. The answers to this question range from &quot;delighted&quot; to &quot;terrible&quot; or 0 to 5.</description>
          <population>ITT set</population>
          <units>Scores 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="119"/>
                <count group_id="O2" value="117"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Month 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.4" spread="0.8"/>
                    <measurement group_id="O2" value="-0.4" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.7" spread="0.8"/>
                    <measurement group_id="O2" value="-0.5" spread="1.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" spread="1.0"/>
                    <measurement group_id="O2" value="-0.6" spread="1.2"/>
                  </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>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0621</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Total Value of Risk Factors for Progression (Total Score of IPSS, Prostate Volume, PSA Level, Maximum Urinary Flow Rate, Residual Urine Volume) Compared to Baseline</title>
        <description>To assess the risk of BPH progression, the following were used: 1) moderate to severe BPH symptoms (ie, IPSS total score&gt; 7); 2) an increase in the volume of the prostate gland (&gt; 30 cm^2); 3) increased PSA level in the blood (≥ 1.4 ng / ml); 4) a decrease in Qmax (&lt;12 ml / s) and 5) a large volume of residual urine (&gt; 200 ml).&#xD;
The total value of risk factors for progression is assessed as the sum of the risk factors that the patient had at the time of inclusion in the study (presence of risk factors = 1 point, absence = 0 points). After 3, 6 and 12 months of treatment, the dynamics of risk factors for progression was assessed: an increase in the severity of the risk factor meant +1, no change = 0, a decrease in the severity of the risk factor of -1.</description>
        <time_frame>Baseline and 3, 6 and 12 months</time_frame>
        <population>ITT set</population>
        <group_list>
          <group group_id="O1">
            <title>Afalaza</title>
            <description>Afalaza (2 tablets twice a day): Safety and Efficacy</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo (2 tablets twice a day): Safety and Efficacy</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Total Value of Risk Factors for Progression (Total Score of IPSS, Prostate Volume, PSA Level, Maximum Urinary Flow Rate, Residual Urine Volume) Compared to Baseline</title>
          <description>To assess the risk of BPH progression, the following were used: 1) moderate to severe BPH symptoms (ie, IPSS total score&gt; 7); 2) an increase in the volume of the prostate gland (&gt; 30 cm^2); 3) increased PSA level in the blood (≥ 1.4 ng / ml); 4) a decrease in Qmax (&lt;12 ml / s) and 5) a large volume of residual urine (&gt; 200 ml).&#xD;
The total value of risk factors for progression is assessed as the sum of the risk factors that the patient had at the time of inclusion in the study (presence of risk factors = 1 point, absence = 0 points). After 3, 6 and 12 months of treatment, the dynamics of risk factors for progression was assessed: an increase in the severity of the risk factor meant +1, no change = 0, a decrease in the severity of the risk factor of -1.</description>
          <population>ITT set</population>
          <units>Scores</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="119"/>
                <count group_id="O2" value="117"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Month 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.9" spread="0.9"/>
                    <measurement group_id="O2" value="-0.7" spread="0.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.7" spread="1.0"/>
                    <measurement group_id="O2" value="-0.4" spread="0.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" spread="1.0"/>
                    <measurement group_id="O2" value="-0.6" spread="1.0"/>
                  </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>0.0142</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Episodes of Acute Urinary Retention, Surgical Intervention During the Observation Period</title>
        <time_frame>12 months</time_frame>
        <population>ITT set</population>
        <group_list>
          <group group_id="O1">
            <title>Afalaza</title>
            <description>Afalaza (2 tablets twice a day): Safety and Efficacy</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo (2 tablets twice a day): Safety and Efficacy</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Episodes of Acute Urinary Retention, Surgical Intervention During the Observation Period</title>
          <population>ITT set</population>
          <units>episodes</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="119"/>
                <count group_id="O2" value="117"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse/Serious adverse events were registered during 12 months of therapy and 30 days after the end of the research</time_frame>
      <desc>Adverse/Serious adverse events were registered in patients of the Full Analysis Set (n=249, Safety Population)</desc>
      <group_list>
        <group group_id="E1">
          <title>Afalaza</title>
          <description>Afalaza (2 tablets twice a day): Safety and Efficiency</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo (2 tablets twice a day): Safety and Efficiency</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, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="124"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia/Meniscus injury/Meniscus operation</sub_title>
                <description>Resection of the medial meniscus and lateral meniscus. Resection of the mediapatulatory fold.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="125"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="124"/>
              </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="25" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="29" subjects_at_risk="124"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Epigastric pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
              </event>
              <event>
                <sub_title>Right-sided inguinal hernia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
              </event>
              <event>
                <sub_title>Heartburn</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="124"/>
              </event>
              <event>
                <sub_title>Swollen tongue</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="124"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="124"/>
              </event>
              <event>
                <sub_title>Chronic gastritis, exacerbation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="124"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia and Depressive weariness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="124"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="124"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
              </event>
              <event>
                <sub_title>Labial herpes</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
              </event>
              <event>
                <sub_title>Acute respiratory viral infection</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="124"/>
              </event>
              <event>
                <sub_title>Acute bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="124"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Prostatic specific antigen increased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="124"/>
              </event>
              <event>
                <sub_title>Blood pressure increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="124"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="124"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Vasomotor rhinitis chronic, exacerbation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
              </event>
              <event>
                <sub_title>Discomfort in the oropharynx</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
              </event>
              <event>
                <sub_title>Сough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic contact dermatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="124"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertensive crisis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="124"/>
              </event>
              <event>
                <sub_title>Hypertensive crisis, accompanied by headache and nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
              </event>
              <event>
                <sub_title>Chronic hemorrhoids, exacerbation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
              </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, Director of Clinical Research and Medical Information</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/NCT01716104
org study id: MMH-AZ-001-I
nct id: NCT01716104
lead sponsor: 
has dmc: No
The purpose of this study is:

        -  To assess safety of Afalaza drug within 12 months in patients with symptoms of benign
           prostatic hyperplasia (BPH) and risk of progression.

        -  To assess efficacy of Afalaza drug within 12 months in patients with symptoms of benign
           prostatic hyperplasia and risk of progression.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in Total IPSS Scores (International Prostate Symptome Score) After 1, 3, 6 and 12 Months Compared to Baseline.
time frame: Baseline, 1, 3, 6 and 12 months
description: The International Prostate Symptom Score (IPSS) is based on the answers to 7 questions concerning urinary symptoms plus one question concerning quality of life (QoL). Each of the seven symptoms includes the assignment of scores from 0 to 5. The total score can therefore range from 0 to 35 points (asymptomatic to very symptomatic). The patient's quality of life (QoL) was evaluated separately in this clinical study.
measure: Change in Dynamics of Irritative Symptoms Evaluated by IPSS (International Prostate Symptome Score) After 1, 3, 6 and 12 Months Compared to Baseline
time frame: Baseline and 1, 3, 6, 12 months
description: The International Prostate Symptom Score (IPSS) is based on the answers to 7 questions concerning urinary symptoms plus one question concerning quality of life (QoL). Each of the seven symptoms includes the assignment of scores from 0 to 5. The total score can therefore range from 0 to 35 points (asymptomatic to very symptomatic). The patient's quality of life (QoL) was evaluated separately in this clinical study.
The sum of IPSS questions 2, 4, and 7 related to irritative symptoms. The total score of irritative symptoms can therefore range from 0 to 15 points (asymptomatic to very symptomatic).
measure: Change in Maximum Urinary Flow Rate After 1, 3, 6 and 12 Months Compared to Baseline
time frame: Baseline and 1, 3, 6 and 12 months
measure: Change in Average Urinary Flow Rate After 1, 3, 6 and 12 Months Compared to Baseline
time frame: Baseline and 1, 3, 6 and 12 months
measure: Percent Change in Mean Values of Prostate Gland Volume at 3, 6 and 12 Months Compared to Baseline
time frame: Baseline and 3, 6 and 12 months
description: Change in the volume of the prostate gland as a percentage of the baseline according to transrectal ultrasound
measure: Change in Mean Values of Micturition Volume at 3, 6 and 12 Months Compared to Baseline
time frame: Baseline and 3, 6 and 12 months
measure: Change in the Mean Values of Residual Urine Volume at 3, 6 and 12 Months Compared to Baseline
time frame: Baseline and 3, 6 and 12 months
description: according to transabdominal ultrasound
measure: Change in Quality of Life (QoL Index of IPSS) at 3, 6 and 12 Months Compared to Baseline
time frame: Baseline and 3, 6 and 12 months
description: Quality of life (QoL) Due to Urinary Symptoms is an eight point of the IPSS scale referred to the patient's quality of life. The answers to this question range from "delighted" to "terrible" or 0 to 5.
measure: Change in Total Value of Risk Factors for Progression (Total Score of IPSS, Prostate Volume, PSA Level, Maximum Urinary Flow Rate, Residual Urine Volume) Compared to Baseline
time frame: Baseline and 3, 6 and 12 months
description: To assess the risk of BPH progression, the following were used: 1) moderate to severe BPH symptoms (ie, IPSS total score> 7); 2) an increase in the volume of the prostate gland (> 30 cm^2); 3) increased PSA level in the blood (≥ 1.4 ng / ml); 4) a decrease in Qmax (<12 ml / s) and 5) a large volume of residual urine (> 200 ml).
The total value of risk factors for progression is assessed as the sum of the risk factors that the patient had at the time of inclusion in the study (presence of risk factors = 1 point, absence = 0 points). After 3, 6 and 12 months of treatment, the dynamics of risk factors for progression was assessed: an increase in the severity of the risk factor meant +1, no change = 0, a decrease in the severity of the risk factor of -1.
measure: Number of Episodes of Acute Urinary Retention, Surgical Intervention During the Observation Period
time frame: 12 months
arm group label: Afalaza (2 tablets twice a day)
arm group type: Experimental
arm group label: Placebo (2 tablets twice a day)
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Afalaza
description: Safety and Efficacy
arm group label: Afalaza (2 tablets twice a day)
intervention type: Drug
intervention name: Placebo
description: Safety and Efficacy
arm group label: Placebo (2 tablets twice a day)
criteria: 
gender: Male
minimum age: 45 Years
maximum age: 60 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Russian Federation
country: Ukraine
responsible party type: Sponsor
mesh term: Prostatic Hyperplasia
mesh term: Hyperplasia
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 