<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/NCT02250612</url>
  </required_header>
  <id_info>
    <org_study_id>SYL040012_IV</org_study_id>
    <secondary_id>2013-002947-27</secondary_id>
    <nct_id>NCT02250612</nct_id>
  </id_info>
  <brief_title>SYL040012, Treatment for Open Angle Glaucoma</brief_title>
  <acronym>SYLTAG</acronym>
  <official_title>A Phase II, Observer Masked, Active Controlled Study of SYL040012 for the Treatment of Elevated Intraocular Pressure in Patients With Open-angle Glaucoma or Ocular Hypertension</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sylentis, S.A.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sylentis, S.A.</source>
  <brief_summary>
    <textblock>
      The purpose of this double-masked, randomized, controlled study is to assess the safety and&#xD;
      ocular hypotensive efficacy of four different doses of SYL040012 (bamosiran) eye drops&#xD;
      compared to Timolol maleate 0.5% after 28 treatment days in patients with elevated&#xD;
      intraocular pressure.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">January 2016</completion_date>
  <primary_completion_date type="Actual">August 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in the Mean Diurnal IOP Within Each Treatment Arm</measure>
    <time_frame>Baseline and Day 28</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Mean Diurnal IOP Within Each Treatment Arm</measure>
    <time_frame>Baseline and Day 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Glaucoma Quality of Life Questionnaire (GQL-15) Scores Within Each Treatment Arm</measure>
    <time_frame>Baseline and Day 29</time_frame>
    <description>The GQL-15 is a 15 item, 4-domain tool. GQL-15 scoring ranges from 0 to 75. Higher scores indicate poorer quality of life.</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">184</enrollment>
  <condition>Open Angle Glaucoma</condition>
  <condition>Ocular Hypertension</condition>
  <arm_group>
    <arm_group_label>SYL040012 (bamosiran) 0.375% eye drops</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 drop in each eye once daily for 28 consecutive days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SYL040012 (bamosiran) 0.750% eye drops</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 drop in each eye once daily for 28 consecutive days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SYL040012 (bamosiran) 1.125% eye drops</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 drop in each eye once daily for 28 consecutive days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SYL040012 (bamosiran) 1.5% eye drops</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 drop in each eye once daily for 28 consecutive days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Timolol maleate 0.5% ophthalmic solution</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>1 drop in each eye twice daily for 28 consecutive days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>1 drop of 0.375% SYL040012 (bamosiran)</intervention_name>
    <arm_group_label>SYL040012 (bamosiran) 0.375% eye drops</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>1 drop of 0.750% SYL040012 (bamosiran)</intervention_name>
    <arm_group_label>SYL040012 (bamosiran) 0.750% eye drops</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>1 drop of 1.125% SYL040012 (bamosiran)</intervention_name>
    <arm_group_label>SYL040012 (bamosiran) 1.125% eye drops</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>1 drop of 1.5% SYL040012 (bamosiran)</intervention_name>
    <arm_group_label>SYL040012 (bamosiran) 1.5% eye drops</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>1 drop of 0.5 % timolol maleate</intervention_name>
    <arm_group_label>Timolol maleate 0.5% ophthalmic solution</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients older than 18 years of either sex&#xD;
&#xD;
          -  Good or fair general health as assessed by the investigator.&#xD;
&#xD;
          -  Signed informed consent prior to any clinical trial-related procedures&#xD;
&#xD;
          -  Diagnosis of open angle glaucoma (OAG) or ocular hypertension (OHT)&#xD;
&#xD;
          -  Post-washout mean IOP above target range&#xD;
&#xD;
          -  BCVA 1.0 logMAR or better by ETDRS in each eye (equivalent to 20/200)&#xD;
&#xD;
          -  Stable visual field&#xD;
&#xD;
          -  Central corneal thickness 480-620 μm&#xD;
&#xD;
          -  Shaffer gonioscopic grade of ≥ 3 (in at least 3 quadrants) in both eyes&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or breastfeeding females&#xD;
&#xD;
          -  Females of childbearing potential not willing to use a medically acceptable&#xD;
             contraceptive method&#xD;
&#xD;
          -  Clinically significant systemic disease&#xD;
&#xD;
          -  Changes of systemic medication that could have a substantial effect on IOP&#xD;
&#xD;
          -  Known hypersensitivity to any component of the formulations&#xD;
&#xD;
          -  Unable to comply with the clinical trial requirements&#xD;
&#xD;
          -  Clinically significant abnormalities in laboratory tests&#xD;
&#xD;
          -  Severe visual field defect&#xD;
&#xD;
          -  Any secondary glaucoma&#xD;
&#xD;
          -  Pseudoexfoliation or pigment dispersion component, history of angle closure or narrow&#xD;
             angles.&#xD;
&#xD;
          -  IOP ≥ 35 mm Hg in any eye&#xD;
&#xD;
          -  Previous non-laser glaucoma surgery or glaucoma laser procedures (e.g., laser&#xD;
             trabeculoplasty) and refractive surgery&#xD;
&#xD;
          -  Any ocular surgery or laser treatment, cataract extraction or ocular trauma within 6&#xD;
             months prior to Baseline&#xD;
&#xD;
          -  Evidence of ocular infection, inflammation, clinically significant blepharitis or&#xD;
             conjunctivitis at baseline (Visit 0), or a history of herpes simplex keratitis&#xD;
&#xD;
          -  Clinically significant ocular disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Sall Research Medical Center</name>
      <address>
        <city>Artesia</city>
        <state>California</state>
        <zip>90701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Bay Eye Associates</name>
      <address>
        <city>Petaluma</city>
        <state>California</state>
        <zip>94954</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eye Care Centers Management, Inc (Clayton Eye Center)</name>
      <address>
        <city>Morrow</city>
        <state>Georgia</state>
        <zip>30260</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taustin Eye Center</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40217</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>East Tallin Central Hospital</name>
      <address>
        <city>Tallin</city>
        <zip>10138</zip>
        <country>Estonia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eye Clinic Dr. Krista Turman</name>
      <address>
        <city>Tallin</city>
        <zip>13419</zip>
        <country>Estonia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tartu University Hospital</name>
      <address>
        <city>Tartu</city>
        <zip>50406</zip>
        <country>Estonia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Freiburg</name>
      <address>
        <city>Freiburg</city>
        <zip>79106</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Clinic Magdeburg</name>
      <address>
        <city>Magdeburg</city>
        <zip>39106</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum der Universität München</name>
      <address>
        <city>München</city>
        <zip>80336</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Münster</name>
      <address>
        <city>Münster</city>
        <zip>D-48149</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Regensburg</name>
      <address>
        <city>Regensburg</city>
        <zip>93053</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Torrevieja</name>
      <address>
        <city>Torrevieja</city>
        <state>Alicante</state>
        <zip>03186</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Jerez</name>
      <address>
        <city>Jerez de la Frontera</city>
        <state>Cádiz</state>
        <zip>11407</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica Universidad Navarra</name>
      <address>
        <city>Pamplona</city>
        <state>Navarra</state>
        <zip>31008</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinic</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Ramón y Cajal</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Clínico San Carlos</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Complejo Hospitalario de Pontevedra</name>
      <address>
        <city>Pontevedra</city>
        <zip>36001</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto de Oftalmobiología Aplicada</name>
      <address>
        <city>Valladolid</city>
        <zip>47011</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Miguel Servet</name>
      <address>
        <city>Zaragoza</city>
        <zip>50009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Estonia</country>
    <country>Germany</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>September 5, 2014</study_first_submitted>
  <study_first_submitted_qc>September 24, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 26, 2014</study_first_posted>
  <results_first_submitted>September 15, 2020</results_first_submitted>
  <results_first_submitted_qc>October 9, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">November 4, 2020</results_first_posted>
  <last_update_submitted>December 11, 2020</last_update_submitted>
  <last_update_submitted_qc>December 11, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 6, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>SYL040012</keyword>
  <keyword>bamosiran</keyword>
  <keyword>siRNA</keyword>
  <keyword>RNAi</keyword>
  <keyword>Glaucoma</keyword>
  <keyword>Ocular hypertension</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glaucoma</mesh_term>
    <mesh_term>Glaucoma, Open-Angle</mesh_term>
    <mesh_term>Ocular Hypertension</mesh_term>
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Timolol</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>SYL040012 (Bamosiran) 0.375% Eye Drops</title>
          <description>1 drop in each eye once daily for 28 consecutive days&#xD;
1 drop of SYL040012 (bamosiran) 0.375 %</description>
        </group>
        <group group_id="P2">
          <title>SYL040012 (Bamosiran) 0.750 % Eye Drops</title>
          <description>1 drop in each eye once daily for 28 consecutive days&#xD;
1 drop of SYL040012 (bamosiran) 0.750 %</description>
        </group>
        <group group_id="P3">
          <title>SYL040012 (Bamosiran) 1.125% Eye Drops</title>
          <description>1 drop in each eye once daily for 28 consecutive days&#xD;
1 drop of SYL040012 (bamosiran) 1.125%</description>
        </group>
        <group group_id="P4">
          <title>SYL040012 (Bamosiran) 1.5% Eye Drops</title>
          <description>1 drop in each eye once daily for 28 consecutive days&#xD;
1 drop of SYL040012 (bamosiran) 1.5%</description>
        </group>
        <group group_id="P5">
          <title>Timolol Maleate 0.5% Ophthalmic Solution</title>
          <description>1 drop in each eye twice daily for 28 consecutive days&#xD;
1 drop of timolol maleate: 0.5 %</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="37"/>
                <participants group_id="P2" count="40"/>
                <participants group_id="P3" count="37"/>
                <participants group_id="P4" count="33"/>
                <participants group_id="P5" count="37"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="36"/>
                <participants group_id="P2" count="38"/>
                <participants group_id="P3" count="35"/>
                <participants group_id="P4" count="33"/>
                <participants group_id="P5" count="36"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>SYL040012 (Bamosiran) Eye Drops Dose A</title>
          <description>1 drop in each eye once daily for 28 consecutive days&#xD;
1 drop of SYL040012 (bamosiran) Dose A</description>
        </group>
        <group group_id="B2">
          <title>SYL040012 (Bamosiran) Eye Drops Dose B</title>
          <description>1 drop in each eye once daily for 28 consecutive days&#xD;
1 drop of SYL040012 (bamosiran) Dose B</description>
        </group>
        <group group_id="B3">
          <title>SYL040012 (Bamosiran) Eye Drops Dose C</title>
          <description>1 drop in each eye once daily for 28 consecutive days&#xD;
1 drop of SYL040012 (bamosiran) Dose C</description>
        </group>
        <group group_id="B4">
          <title>SYL040012 (Bamosiran) Eye Drops Dose D</title>
          <description>1 drop in each eye once daily for 28 consecutive days&#xD;
1 drop of SYL040012 (bamosiran) Dose D</description>
        </group>
        <group group_id="B5">
          <title>Timolol Maleate 0.5% Ophthalmic Solution</title>
          <description>1 drop in each eye twice daily for 28 consecutive days&#xD;
1 drop of timolol maleate: 0.5 %</description>
        </group>
        <group group_id="B6">
          <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="37"/>
            <count group_id="B2" value="40"/>
            <count group_id="B3" value="37"/>
            <count group_id="B4" value="33"/>
            <count group_id="B5" value="37"/>
            <count group_id="B6" value="184"/>
          </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="60.7" spread="10.4"/>
                    <measurement group_id="B2" value="59.4" spread="12.9"/>
                    <measurement group_id="B3" value="61.5" spread="10.1"/>
                    <measurement group_id="B4" value="62.4" spread="11.1"/>
                    <measurement group_id="B5" value="60.2" spread="11.5"/>
                    <measurement group_id="B6" value="60.8" spread="11.18"/>
                  </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="25"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="22"/>
                    <measurement group_id="B4" value="24"/>
                    <measurement group_id="B5" value="24"/>
                    <measurement group_id="B6" value="119"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="9"/>
                    <measurement group_id="B5" value="13"/>
                    <measurement group_id="B6" value="65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in the Mean Diurnal IOP Within Each Treatment Arm</title>
        <time_frame>Baseline and Day 28</time_frame>
        <group_list>
          <group group_id="O1">
            <title>SYL040012 (Bamosiran) 0.375 % Eye Drops</title>
            <description>1 drop in each eye once daily for 28 consecutive days&#xD;
1 drop of SYL040012 (bamosiran) 0.375 %</description>
          </group>
          <group group_id="O2">
            <title>SYL040012 (Bamosiran) 0.75 % Eye Drops</title>
            <description>1 drop in each eye once daily for 28 consecutive days&#xD;
1 drop of SYL040012 (bamosiran) 0.75%</description>
          </group>
          <group group_id="O3">
            <title>SYL040012 (Bamosiran) 1.125% Eye Drops</title>
            <description>1 drop in each eye once daily for 28 consecutive days&#xD;
1 drop of SYL040012 (bamosiran) 1.125%</description>
          </group>
          <group group_id="O4">
            <title>SYL040012 (Bamosiran) 1.5% Eye Drops</title>
            <description>1 drop in each eye once daily for 28 consecutive days&#xD;
1 drop of SYL040012 (bamosiran) 1.5%</description>
          </group>
          <group group_id="O5">
            <title>Timolol Maleate 0.5% Ophthalmic Solution</title>
            <description>1 drop in each eye twice daily for 28 consecutive days&#xD;
1 drop of timolol maleate: 0.5 %</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Mean Diurnal IOP Within Each Treatment Arm</title>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
                <count group_id="O2" value="38"/>
                <count group_id="O3" value="35"/>
                <count group_id="O4" value="33"/>
                <count group_id="O5" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.4" spread="2.6"/>
                    <measurement group_id="O2" value="-3.2" spread="3.9"/>
                    <measurement group_id="O3" value="-3.1" spread="2.5"/>
                    <measurement group_id="O4" value="-3.1" spread="3.2"/>
                    <measurement group_id="O5" value="-6.1" spread="2.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.93</p_value>
            <method>ANCOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.92</p_value>
            <method>ANCOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.23</p_value>
            <method>ANCOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.85</p_value>
            <method>ANCOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.25</p_value>
            <method>ANCOVA</method>
          </analysis>
          <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>0.18</p_value>
            <method>ANCOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Mean Diurnal IOP Within Each Treatment Arm</title>
        <time_frame>Baseline and Day 14</time_frame>
        <group_list>
          <group group_id="O1">
            <title>SYL040012 (Bamosiran) 1.5% Eye Drops</title>
            <description>1 drop in each eye once daily for 28 consecutive days&#xD;
1 drop of SYL040012 (bamosiran) 1.5%</description>
          </group>
          <group group_id="O2">
            <title>SYL040012 (Bamosiran) Eye Drops 1.125%</title>
            <description>1 drop in each eye once daily for 28 consecutive days&#xD;
1 drop of SYL040012 (bamosiran) 1.125%</description>
          </group>
          <group group_id="O3">
            <title>SYL040012 (Bamosiran) Eye Drops 0.75%</title>
            <description>1 drop in each eye once daily for 28 consecutive days&#xD;
1 drop of SYL040012 (bamosiran) 0.75%</description>
          </group>
          <group group_id="O4">
            <title>SYL040012 (Bamosiran) 0.375 % Eye Drops</title>
            <description>1 drop in each eye once daily for 28 consecutive days&#xD;
1 drop of SYL040012 (bamosiran) 0.375 %</description>
          </group>
          <group group_id="O5">
            <title>Timolol Maleate 0.5% Ophthalmic Solution</title>
            <description>1 drop in each eye twice daily for 28 consecutive days&#xD;
1 drop of timolol maleate: 0.5 %</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Mean Diurnal IOP Within Each Treatment Arm</title>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
                <count group_id="O2" value="38"/>
                <count group_id="O3" value="35"/>
                <count group_id="O4" value="33"/>
                <count group_id="O5" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.4" spread="2.6"/>
                    <measurement group_id="O2" value="-2.9" spread="2.4"/>
                    <measurement group_id="O3" value="-2.5" spread="2.1"/>
                    <measurement group_id="O4" value="-2.4" spread="3.1"/>
                    <measurement group_id="O5" value="-5.8" spread="1.9"/>
                  </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>0.94</p_value>
            <method>ANCOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.38</p_value>
            <method>ANCOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.85</p_value>
            <method>ANCOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.412</p_value>
            <method>ANCOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.79</p_value>
            <method>ANCOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.28</p_value>
            <method>ANCOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Glaucoma Quality of Life Questionnaire (GQL-15) Scores Within Each Treatment Arm</title>
        <description>The GQL-15 is a 15 item, 4-domain tool. GQL-15 scoring ranges from 0 to 75. Higher scores indicate poorer quality of life.</description>
        <time_frame>Baseline and Day 29</time_frame>
        <group_list>
          <group group_id="O1">
            <title>SYL040012 (Bamosiran) 1.5% Eye Drops</title>
            <description>1 drop in each eye once daily for 28 consecutive days&#xD;
1 drop of SYL040012 (bamosiran) 1.5%</description>
          </group>
          <group group_id="O2">
            <title>SYL040012 (Bamosiran) 1.125% Eye Drops</title>
            <description>1 drop in each eye once daily for 28 consecutive days&#xD;
1 drop of SYL040012 (bamosiran) 1.125%</description>
          </group>
          <group group_id="O3">
            <title>SYL040012 (Bamosiran) 0.75% Eye Drops</title>
            <description>1 drop in each eye once daily for 28 consecutive days&#xD;
1 drop of SYL040012 (bamosiran) 0.75%</description>
          </group>
          <group group_id="O4">
            <title>SYL040012 (Bamosiran) Eye Drops 0.375%</title>
            <description>1 drop in each eye once daily for 28 consecutive days&#xD;
1 drop of SYL040012 (bamosiran) 0.375%</description>
          </group>
          <group group_id="O5">
            <title>Timolol Maleate 0.5% Ophthalmic Solution</title>
            <description>1 drop in each eye twice daily for 28 consecutive days&#xD;
1 drop of timolol maleate: 0.5 %</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Glaucoma Quality of Life Questionnaire (GQL-15) Scores Within Each Treatment Arm</title>
          <description>The GQL-15 is a 15 item, 4-domain tool. GQL-15 scoring ranges from 0 to 75. Higher scores indicate poorer quality of life.</description>
          <units>units 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="36"/>
                <count group_id="O2" value="38"/>
                <count group_id="O3" value="35"/>
                <count group_id="O4" value="33"/>
                <count group_id="O5" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20" spread="8.28"/>
                    <measurement group_id="O2" value="20.7" spread="7.68"/>
                    <measurement group_id="O3" value="19.4" spread="6.34"/>
                    <measurement group_id="O4" value="22" spread="9.65"/>
                    <measurement group_id="O5" value="18.7" spread="6.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>28 days</time_frame>
      <group_list>
        <group group_id="E1">
          <title>SYL040012 (Bamosiran) Eye Drops Dose A</title>
          <description>1 drop in each eye once daily for 28 consecutive days&#xD;
1 drop of SYL040012 (bamosiran) Dose A</description>
        </group>
        <group group_id="E2">
          <title>SYL040012 (Bamosiran) Eye Drops Dose B</title>
          <description>1 drop in each eye once daily for 28 consecutive days&#xD;
1 drop of SYL040012 (bamosiran) Dose B</description>
        </group>
        <group group_id="E3">
          <title>SYL040012 (Bamosiran) Eye Drops Dose C</title>
          <description>1 drop in each eye once daily for 28 consecutive days&#xD;
1 drop of SYL040012 (bamosiran) Dose C</description>
        </group>
        <group group_id="E4">
          <title>SYL040012 (Bamosiran) Eye Drops Dose D</title>
          <description>1 drop in each eye once daily for 28 consecutive days&#xD;
1 drop of SYL040012 (bamosiran) Dose D</description>
        </group>
        <group group_id="E5">
          <title>Timolol Maleate 0.5% Ophthalmic Solution</title>
          <description>1 drop in each eye twice daily for 28 consecutive days&#xD;
1 drop of timolol maleate: 0.5 %</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (18.0)</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="4" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="37"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Conjunctival hyperaemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="37"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Eye pruritus</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Lacrimation increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Ocular discomfort</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="40"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Instillation site pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" events="5" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="37"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="37"/>
              </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 NOT 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>Clinical Trials Department</name_or_title>
      <organization>Sylentis</organization>
      <email>info@sylentis.com</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/NCT02250612
org study id: SYL040012_IV
secondary id: 2013-002947-27
nct id: NCT02250612
lead sponsor: 
The purpose of this double-masked, randomized, controlled study is to assess the safety and
      ocular hypotensive efficacy of four different doses of SYL040012 (bamosiran) eye drops
      compared to Timolol maleate 0.5% after 28 treatment days in patients with elevated
      intraocular pressure.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change From Baseline in the Mean Diurnal IOP Within Each Treatment Arm
time frame: Baseline and Day 28
measure: Change From Baseline in the Mean Diurnal IOP Within Each Treatment Arm
time frame: Baseline and Day 14
measure: Change From Baseline in the Glaucoma Quality of Life Questionnaire (GQL-15) Scores Within Each Treatment Arm
time frame: Baseline and Day 29
description: The GQL-15 is a 15 item, 4-domain tool. GQL-15 scoring ranges from 0 to 75. Higher scores indicate poorer quality of life.
arm group label: SYL040012 (bamosiran) 0.375% eye drops
arm group type: Experimental
description: 1 drop in each eye once daily for 28 consecutive days
arm group label: SYL040012 (bamosiran) 0.750% eye drops
arm group type: Experimental
description: 1 drop in each eye once daily for 28 consecutive days
arm group label: SYL040012 (bamosiran) 1.125% eye drops
arm group type: Experimental
description: 1 drop in each eye once daily for 28 consecutive days
arm group label: SYL040012 (bamosiran) 1.5% eye drops
arm group type: Experimental
description: 1 drop in each eye once daily for 28 consecutive days
arm group label: Timolol maleate 0.5% ophthalmic solution
arm group type: Active Comparator
description: 1 drop in each eye twice daily for 28 consecutive days
intervention type: Drug
intervention name: 1 drop of 0.375% SYL040012 (bamosiran)
arm group label: SYL040012 (bamosiran) 0.375% eye drops
intervention type: Drug
intervention name: 1 drop of 0.750% SYL040012 (bamosiran)
arm group label: SYL040012 (bamosiran) 0.750% eye drops
intervention type: Drug
intervention name: 1 drop of 1.125% SYL040012 (bamosiran)
arm group label: SYL040012 (bamosiran) 1.125% eye drops
intervention type: Drug
intervention name: 1 drop of 1.5% SYL040012 (bamosiran)
arm group label: SYL040012 (bamosiran) 1.5% eye drops
intervention type: Drug
intervention name: 1 drop of 0.5 % timolol maleate
arm group label: Timolol maleate 0.5% ophthalmic solution
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Estonia
country: Germany
country: Spain
country: United States
responsible party type: Sponsor
mesh term: Glaucoma
mesh term: Glaucoma, Open-Angle
mesh term: Ocular Hypertension
mesh term: Hypertension
mesh term: Timolol
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 