<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/NCT03238963</url>
  </required_header>
  <id_info>
    <org_study_id>1386-0012</org_study_id>
    <secondary_id>2016-002971-91</secondary_id>
    <secondary_id>1386.12</secondary_id>
    <nct_id>NCT03238963</nct_id>
  </id_info>
  <brief_title>A Study That Tests BI 1467335 in Patients With Diabetic Eye Disease (Diabetic Retinopathy). It Looks at the Way BI 1467335 is Taken up, the Effects it Has, and How Well it is Tolerated.</brief_title>
  <acronym>ROBIN</acronym>
  <official_title>A Randomized, Double-masked, Placebo-controlled Exploratory Study to Evaluate Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Orally Administered BI 1467335 for 12 Weeks With a 12 Week Follow up Period in Patients With Non-proliferative Diabetic Retinopathy Without Center-involved Diabetic Macular Edema (ROBIN Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main objective is to evaluate ocular and systemic safety and tolerability of BI 1467335&#xD;
      as well as whether BI 1467335 monotherapy has a potential to improve retinal lesions in&#xD;
      patients with moderately severe Non-proliferative diabetic retinopathy (NPDR) (DRSS level 47)&#xD;
      or severe Non-proliferative diabetic retinopathy (NPDR) (DRSS level 53), without&#xD;
      Center-involved diabetic macular edema (CI-DME)&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 19, 2017</start_date>
  <completion_date type="Actual">May 14, 2020</completion_date>
  <primary_completion_date type="Actual">May 14, 2020</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants With Any Ocular Adverse Events Over the On-treatment Period</measure>
    <time_frame>On-treatment period: from first dose of study drug until end of follow-up period, up to 24 weeks.</time_frame>
    <description>Percentage of participants with any ocular adverse events over the on-treatment period was reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With at Least 2 Steps Improvement From Baseline in the Study Eye on the Diabetic Retinopathy Severity Scale (DRSS) at Week 12</measure>
    <time_frame>At baseline and at Week 12.</time_frame>
    <description>7-field or modified 4-field digital fundus photographs was obtained from both eyes by a qualified person according to the imaging manual to collect all data for the assessment of the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS). The images was sent to the independent central reading center who performs the grading on the basis of the DRSS. The DRSS ranges from level 10 (Diabetic retinopathy absent) to level 85 (advanced proliferative Diabetic retinopathy).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Adverse Events Other Than Ocular Adverse Events Over On-treatment Period</measure>
    <time_frame>On-treatment period: from first dose of study drug until end of follow-up period, up to 24 weeks.</time_frame>
    <description>Percentage of participants with adverse events other than ocular adverse events over on-treatment period was reported.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">79</enrollment>
  <condition>Diabetic Retinopathy</condition>
  <arm_group>
    <arm_group_label>BI 1467335</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 1467335</intervention_name>
    <description>Once daily</description>
    <arm_group_label>BI 1467335</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Once daily</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Of legal age (according to local legislation, usually ≥ 18 years) at screening&#xD;
&#xD;
          -  Male or female patients. Women of childbearing potential (WOCBP) must be ready and&#xD;
             able to use two methods of contraception with at least one of them being a highly&#xD;
             effective method of birth control per ICH M3 (R2) that result in a low failure rate of&#xD;
             less than 1% per year when used consistently and correctly. A list of contraception&#xD;
             methods meeting these criteria is provided in the patient information.&#xD;
&#xD;
          -  Diagnosis of diabetes mellitus (type 1 or type 2):&#xD;
&#xD;
             --Documented diabetes by American Diabetes Association (ADA) and/or World Health&#xD;
             Organization criteria&#xD;
&#xD;
          -  Glycosylated hemoglobin (HbA1c) ≤ 12% at screening&#xD;
&#xD;
          -  Non-proliferative diabetic retinopathy (NPDR) without center-involved diabetic macular&#xD;
             edema (CI-DME) in the study eye at screening with NPDR level 47 or level 53, as&#xD;
             determined by the Central reading center (CRC) by using the DR severity scale (DRSS)&#xD;
&#xD;
          -  Best corrected visual acuity ETDRS letter score ≥ 70 letters in the study eye at&#xD;
             screening&#xD;
&#xD;
          -  Media clarity, pupillary dilation and individual cooperation sufficient for adequate&#xD;
             retinal examination including fundus photographs and Optical Coherence Tomography&#xD;
             (OCT)&#xD;
&#xD;
          -  Signed and dated written informed consent in accordance with ICH-GCP and local&#xD;
             legislation prior to admission to the trial&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Cataract surgery performed within 6 months prior to screening or planned during the&#xD;
             trial in the study eye; or any additional eye disease in the study eye that, in the&#xD;
             opinion of the investigator,could compromise or alter visual acuity during the course&#xD;
             of the study (e.g. vein occlusion, uncontrolled intraocular pressure (IOP) &gt;24 mmHg on&#xD;
             optimal medical treatment, glaucoma with visual field loss, uveitis or other ocular&#xD;
             inflammatory disease,vitreomacular traction, monocular vision, history of ischemic&#xD;
             optic neuropathy, or genetic disorders such as retinitis pigmentosa)&#xD;
&#xD;
          -  Active center-involved DME (CI-DME) on clinical examination and Optical Coherence&#xD;
             Tomography (OCT) central subfield thickness in the study eye above 300 μm as measured&#xD;
             by Optovue OCT or above 320 μm as measured by Heidelberg OCT&#xD;
&#xD;
          -  Anterior segment and vitreous abnormalities in the study eye that would compromise the&#xD;
             adequate assessment of the best corrected visual acuity or an adequate examination of&#xD;
             the posterior pole&#xD;
&#xD;
          -  Evidence of neovascularization on clinical examination including active&#xD;
             neovascularization of the iris (small iris tufts are not an exclusion) or angle&#xD;
             neovascularization in the study eye, ruled out by gonioscopy (documented in the last 4&#xD;
             weeks before screening or performed at screening)&#xD;
&#xD;
          -  Prior pan-retinal photocoagulation (defined as ≥ 100 burns placed previously outside&#xD;
             of the posterior pole) in the study eye&#xD;
&#xD;
          -  Treatment of either DME or DR with macular laser within 3 months prior to screening,&#xD;
             or intraocular injections of medication within 6 months prior to screening, and no&#xD;
             more than 4 prior intraocular injections in the study eye at any time in the past&#xD;
&#xD;
          -  Patients treated with Monoamine Oxidase (MAO) inhibitors or drugs that may have&#xD;
             potential side effects due to MAO inhibition&#xD;
&#xD;
          -  Current or planned, during the trial, use of medications known to be toxic to the&#xD;
             retina, lens or optic nerve, or cause vision loss&#xD;
&#xD;
          -  Patients who must or wish to continue the intake of other restricted medications or&#xD;
             any drug considered likely to interfere with the safe conduct of the trial&#xD;
&#xD;
          -  Estimated Glomerular filtration rate (eGFR) &lt; 60 mL/min/1.73m2 calculated by Chronic&#xD;
             Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at screening, or where&#xD;
             the investigator expects filtration rate is likely to drop below 60 mL/min/1.73m2&#xD;
             during the trial&#xD;
&#xD;
          -  Alanine transaminase (ALT) or aspartate transaminase (AST) greater than 2.0-fold the&#xD;
             upper limit of normal, or total bilirubin &gt; 1.5x upper limit of normal.&#xD;
&#xD;
          -  Uncontrolled arterial hypertension defined as a single measurement of systolic blood&#xD;
             pressure &gt;180 mmHg, or two consecutive measurements of systolic blood pressure &gt; 160&#xD;
             mmHg and/or diastolic blood pressure &gt;100 mmHg on optimal medical regimen at&#xD;
             screening. If blood pressure is brought to ≤ 160/100 mmHg by antihypertensive&#xD;
             treatment until randomization, individual can become eligible.&#xD;
&#xD;
          -  Wolff-Parkinson-White Syndrome, baseline QTc &gt; 450 ms (Fridericia's formula), family&#xD;
             history of long QT, or on medication prolonging QT time at screening or planned&#xD;
             initiation during the trial&#xD;
&#xD;
          -  Diagnosis of a serious or unstable systemic or eye disease and other conditions that,&#xD;
             in the clinical judgment of the investigator, are likely to interfere with the&#xD;
             analyses of safety and efficacy in this study. Patients with an expected life&#xD;
             expectancy of less than 2 years are also excluded.&#xD;
&#xD;
          -  Active known or suspected chronic or relevant acute infections, such as HIV (Human&#xD;
             Immunodeficiency Virus)\viral hepatitis, or tuberculosis. QuantiFERON® TB test and HBs&#xD;
             Ag test will be performed during screening. Patients with a positive test result may&#xD;
             participate in the study if further work up (according to local practice/guidelines)&#xD;
             establishes conclusively that the patient has no evidence of active infection.&#xD;
&#xD;
          -  Any documented active or suspected malignancy or history of malignancy within 5 years&#xD;
             prior to screening, except appropriately treated basal cell carcinoma of the skin or&#xD;
             in situ carcinoma of uterine cervix.&#xD;
&#xD;
          -  Chronic alcohol or drug abuse or any condition that, in the investigator's opinion,&#xD;
             makes them an unreliable study participant or unlikely to complete the trial&#xD;
&#xD;
          -  Known hypersensitivity to any component of the trial drug and/or allergy to&#xD;
             fluorescein dye&#xD;
&#xD;
          -  Major surgery (major according to the investigator's assessment) performed within 12&#xD;
             weeks prior to randomization or planned during the trial, e.g. hip replacement&#xD;
&#xD;
          -  Currently enrolled in another investigational drug trial, or less than 30 days or 5&#xD;
             times half-life of the investigational drug, whichever is longer, since ending another&#xD;
             investigational drug trial from the screening visit in this trial or receiving other&#xD;
             investigational treatment(s); patients participating in a purely observational trial&#xD;
             will not be excluded.&#xD;
&#xD;
          -  Previous randomization in this trial&#xD;
&#xD;
          -  Women who are pregnant, nursing, or who plan to become pregnant while in the trial&#xD;
&#xD;
          -  Any other clinical condition that, in the opinion of the investigator, would&#xD;
             jeopardize patient safety while participating in this clinical trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Trinity Research</name>
      <address>
        <city>Dothan</city>
        <state>Alabama</state>
        <zip>36301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retinal Research Institute, LLC</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85053</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina-Vitreous Associates Medical Group</name>
      <address>
        <city>Beverly Hills</city>
        <state>California</state>
        <zip>90211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford University Medical Center</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Retina Institute</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern Medical Group</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Raj K. Maturi, MD PC</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46290</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cumberland Valley Retina Consultants, PC.</name>
      <address>
        <city>Hagerstown</city>
        <state>Maryland</state>
        <zip>21740</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NJRetina</name>
      <address>
        <city>Teaneck</city>
        <state>New Jersey</state>
        <zip>07666</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York Eye and Ear Infirmary of Mount Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10003</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charlotte Eye Ear Nose and Throat Associates, PA</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Research Institute of Texas</name>
      <address>
        <city>Abilene</city>
        <state>Texas</state>
        <zip>79606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Research Center, PLLC</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Consultants of Houston, PA</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LKH-Univ. Hospital Graz</name>
      <address>
        <city>Graz</city>
        <zip>8036</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Interbalkan Medical Center of Thessaloniki</name>
      <address>
        <city>Thessaloniki</city>
        <zip>57001</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione Centro San Raffaele del Monte Tabor</name>
      <address>
        <city>Milano</city>
        <zip>20132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRCCS Fondazione Bietti</name>
      <address>
        <city>Roma</city>
        <zip>00198</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oslo Universitetssykehus HF, Ullevål sykehus</name>
      <address>
        <city>Oslo</city>
        <zip>N-0407</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHUC - Centro Hospitalar e Universitário de Coimbra, EPE</name>
      <address>
        <city>Coimbra</city>
        <zip>3000-075</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Espaço Médico de Coimbra</name>
      <address>
        <city>Coimbra</city>
        <zip>3030-163</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHULC, EPE - Hospital Sto. António Capuchos</name>
      <address>
        <city>Lisboa</city>
        <zip>1169-050</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Dos de Maig</name>
      <address>
        <city>Barcelona</city>
        <zip>08025</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clínico San Carlos</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Miguel Servet</name>
      <address>
        <city>Zaragoza</city>
        <zip>50009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bradford Royal Infirmary</name>
      <address>
        <city>Bradford</city>
        <zip>BD9 6RJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bristol Eye Hospital</name>
      <address>
        <city>Bristol</city>
        <zip>BS1 2LX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Frimley Park Hospital</name>
      <address>
        <city>Frimley</city>
        <zip>GU16 7UJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Moorfields Eye Hospital</name>
      <address>
        <city>London</city>
        <zip>EC1V 2PD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Victoria Infirmary</name>
      <address>
        <city>Newcastle upon Tyne</city>
        <zip>NE1 4LP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital of St Cross</name>
      <address>
        <city>Rugby</city>
        <zip>CV22 5PX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sunderland Eye Infirmary</name>
      <address>
        <city>Sunderland</city>
        <zip>SR2 9HP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>Greece</country>
    <country>Italy</country>
    <country>Norway</country>
    <country>Portugal</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>France</country>
    <country>Germany</country>
  </removed_countries>
  <link>
    <url>https://www.mystudywindow.com</url>
    <description>Related Info</description>
  </link>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>August 1, 2017</study_first_submitted>
  <study_first_submitted_qc>August 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 3, 2017</study_first_posted>
  <results_first_submitted>May 11, 2021</results_first_submitted>
  <results_first_submitted_qc>May 11, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">June 4, 2021</results_first_posted>
  <last_update_submitted>May 11, 2021</last_update_submitted>
  <last_update_submitted_qc>May 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 4, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Retinal Diseases</mesh_term>
    <mesh_term>Diabetic Retinopathy</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>April 11, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/63/NCT03238963/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 29, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/63/NCT03238963/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>A study evaluated safety and tolerability of 12-week treatment of oral BI 1467335 compared to placebo in patients with moderately severe to severe non-proliferative diabetic retinopathy without center-involved diabetic macular edema and explored the efficacy of BI 1467335 on improvement of diabetic retinopathy.</recruitment_details>
      <pre_assignment_details>All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria.&#xD;
Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>BI 1467335 10 mg</title>
          <description>2 film coated tablets of 5 milligram (mg) BI 1467335 (Total: 10 mg) were taken orally once daily for a treatment period of 12 weeks with 12 weeks of follow-up.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>2 film coated tablets of matching placebo were taken orally once daily for a treatment period of 12 weeks with 12 weeks of follow-up.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="40"/>
                <participants group_id="P2" count="39"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="35"/>
                <participants group_id="P2" count="37"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Prohibited medication given due to hospital stay</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Treated set (TS): the TS consists of all patients who were treated with at least one dose of trial drug (BI 1467335 or placebo).</population>
      <group_list>
        <group group_id="B1">
          <title>BI 1467335 10 mg</title>
          <description>2 film coated tablets of 5 milligram (mg) BI 1467335 (Total: 10 mg) were taken orally once daily for a treatment period of 12 weeks with 12 weeks of follow-up.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>2 film coated tablets of matching placebo were taken orally once daily for a treatment period of 12 weeks with 12 weeks of follow-up.</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="40"/>
            <count group_id="B2" value="39"/>
            <count group_id="B3" value="79"/>
          </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="52.5" spread="10.8"/>
                    <measurement group_id="B2" value="53.1" spread="13.3"/>
                    <measurement group_id="B3" value="52.8" spread="12.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="46"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</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_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</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>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="36"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="67"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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>Unknown or Not Reported</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_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Any Ocular Adverse Events Over the On-treatment Period</title>
        <description>Percentage of participants with any ocular adverse events over the on-treatment period was reported.</description>
        <time_frame>On-treatment period: from first dose of study drug until end of follow-up period, up to 24 weeks.</time_frame>
        <population>Treated set (TS): the TS consists of all patients who were treated with at least one dose of trial drug (BI 1467335 or placebo).</population>
        <group_list>
          <group group_id="O1">
            <title>BI 1467335 10 mg</title>
            <description>2 film coated tablets of 5 milligram (mg) BI 1467335 (Total: 10 mg) were taken orally once daily for a treatment period of 12 weeks with 12 weeks of follow-up.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>2 film coated tablets of matching placebo were taken orally once daily for a treatment period of 12 weeks with 12 weeks of follow-up.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Any Ocular Adverse Events Over the On-treatment Period</title>
          <description>Percentage of participants with any ocular adverse events over the on-treatment period was reported.</description>
          <population>Treated set (TS): the TS consists of all patients who were treated with at least one dose of trial drug (BI 1467335 or placebo).</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
                <count group_id="O2" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.0"/>
                    <measurement group_id="O2" value="23.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With at Least 2 Steps Improvement From Baseline in the Study Eye on the Diabetic Retinopathy Severity Scale (DRSS) at Week 12</title>
        <description>7-field or modified 4-field digital fundus photographs was obtained from both eyes by a qualified person according to the imaging manual to collect all data for the assessment of the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS). The images was sent to the independent central reading center who performs the grading on the basis of the DRSS. The DRSS ranges from level 10 (Diabetic retinopathy absent) to level 85 (advanced proliferative Diabetic retinopathy).</description>
        <time_frame>At baseline and at Week 12.</time_frame>
        <population>Full analysis set (FAS): the FAS consists of all the patients who were randomized, treated with at least one dose of BI 1467335/placebo and have baseline and one on-treatment Diabetic Retinopathy Severity Scale assessment. Only patients with non-missing endpoint results were included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>BI 1467335 10 mg</title>
            <description>2 film coated tablets of 5 milligram (mg) BI 1467335 (Total: 10 mg) were taken orally once daily for a treatment period of 12 weeks with 12 weeks of follow-up.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>2 film coated tablets of matching placebo were taken orally once daily for a treatment period of 12 weeks with 12 weeks of follow-up.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With at Least 2 Steps Improvement From Baseline in the Study Eye on the Diabetic Retinopathy Severity Scale (DRSS) at Week 12</title>
          <description>7-field or modified 4-field digital fundus photographs was obtained from both eyes by a qualified person according to the imaging manual to collect all data for the assessment of the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS). The images was sent to the independent central reading center who performs the grading on the basis of the DRSS. The DRSS ranges from level 10 (Diabetic retinopathy absent) to level 85 (advanced proliferative Diabetic retinopathy).</description>
          <population>Full analysis set (FAS): the FAS consists of all the patients who were randomized, treated with at least one dose of BI 1467335/placebo and have baseline and one on-treatment Diabetic Retinopathy Severity Scale assessment. Only patients with non-missing endpoint results were included in the analysis.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.7"/>
                    <measurement group_id="O2" value="0.0"/>
                  </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>Other</non_inferiority_type>
            <param_type>Risk Difference (RD)</param_type>
            <param_value>0.057</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.039</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.053</ci_lower_limit>
            <ci_upper_limit>0.192</ci_upper_limit>
            <estimate_desc>Risk difference of BI 1467335 10 milligram (mg) group minus Placebo group.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Adverse Events Other Than Ocular Adverse Events Over On-treatment Period</title>
        <description>Percentage of participants with adverse events other than ocular adverse events over on-treatment period was reported.</description>
        <time_frame>On-treatment period: from first dose of study drug until end of follow-up period, up to 24 weeks.</time_frame>
        <population>Treated set (TS): the TS consists of all patients who were treated with at least one dose of trial drug (BI 1467335 or placebo).</population>
        <group_list>
          <group group_id="O1">
            <title>BI 1467335 10 mg</title>
            <description>2 film coated tablets of 5 milligram (mg) BI 1467335 (Total: 10 mg) were taken orally once daily for a treatment period of 12 weeks with 12 weeks of follow-up.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>2 film coated tablets of matching placebo were taken orally once daily for a treatment period of 12 weeks with 12 weeks of follow-up.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Adverse Events Other Than Ocular Adverse Events Over On-treatment Period</title>
          <description>Percentage of participants with adverse events other than ocular adverse events over on-treatment period was reported.</description>
          <population>Treated set (TS): the TS consists of all patients who were treated with at least one dose of trial drug (BI 1467335 or placebo).</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
                <count group_id="O2" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="55.0"/>
                    <measurement group_id="O2" value="82.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From first dose of study drug until end of follow-up period, up to 24 weeks.</time_frame>
      <desc>Treated set (TS): the TS consists of all patients who were treated with at least one dose of trial drug (BI 1467335 or placebo).</desc>
      <group_list>
        <group group_id="E1">
          <title>BI 1467335 10 mg</title>
          <description>2 film coated tablets of 5 milligram (mg) BI 1467335 (Total: 10 mg) were taken orally once daily for a treatment period of 12 weeks with 12 weeks of follow-up.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>2 film coated tablets of matching placebo were taken orally once daily for a treatment period of 12 weeks with 12 weeks of follow-up.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 23.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Visual acuity reduced</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Impaired gastric emptying</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Pancreatitis chronic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis acute</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Liver function test increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Cervix carcinoma stage 0</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Prostate cancer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysarthria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 23.0</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="16" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="25" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetic retinopathy</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Localised infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Blood glucose increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Glucose urine present</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Protein urine present</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="39"/>
              </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>Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results.&#xD;
Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days.&#xD;
BI may request a delay of the publication in order to protect BI's intellectual property rights.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Boehringer Ingelheim Call Center</name_or_title>
      <organization>Boehringer Ingelheim</organization>
      <phone>1-800-243-0127</phone>
      <email>clintriage.rdg@boehringer-ingelheim.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/NCT03238963
org study id: 1386-0012
secondary id: 2016-002971-91
secondary id: 1386.12
nct id: NCT03238963
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The main objective is to evaluate ocular and systemic safety and tolerability of BI 1467335
      as well as whether BI 1467335 monotherapy has a potential to improve retinal lesions in
      patients with moderately severe Non-proliferative diabetic retinopathy (NPDR) (DRSS level 47)
      or severe Non-proliferative diabetic retinopathy (NPDR) (DRSS level 53), without
      Center-involved diabetic macular edema (CI-DME)
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Percentage of Participants With Any Ocular Adverse Events Over the On-treatment Period
time frame: On-treatment period: from first dose of study drug until end of follow-up period, up to 24 weeks.
description: Percentage of participants with any ocular adverse events over the on-treatment period was reported.
measure: Percentage of Participants With at Least 2 Steps Improvement From Baseline in the Study Eye on the Diabetic Retinopathy Severity Scale (DRSS) at Week 12
time frame: At baseline and at Week 12.
description: 7-field or modified 4-field digital fundus photographs was obtained from both eyes by a qualified person according to the imaging manual to collect all data for the assessment of the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS). The images was sent to the independent central reading center who performs the grading on the basis of the DRSS. The DRSS ranges from level 10 (Diabetic retinopathy absent) to level 85 (advanced proliferative Diabetic retinopathy).
measure: Percentage of Participants With Adverse Events Other Than Ocular Adverse Events Over On-treatment Period
time frame: On-treatment period: from first dose of study drug until end of follow-up period, up to 24 weeks.
description: Percentage of participants with adverse events other than ocular adverse events over on-treatment period was reported.
arm group label: BI 1467335
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: BI 1467335
description: Once daily
arm group label: BI 1467335
intervention type: Drug
intervention name: Placebo
description: Once daily
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Austria
country: Greece
country: Italy
country: Norway
country: Portugal
country: Spain
country: United Kingdom
country: United States
country: France
country: Germany
url: https://www.mystudywindow.com
description: Related Info
responsible party type: Sponsor
mesh term: Retinal Diseases
mesh term: Diabetic Retinopathy
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 