xml: <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/NCT05973305</url>
    </required_header>
    <id_info>
      <org_study_id>DORZOL-10/2015</org_study_id>
      <nct_id>NCT05973305</nct_id>
    </id_info>
    <brief_title>Comparative Study of Dorzol Eye Drops, 20 mg/ml Versus Trusopt® Eye Drops, 20 mg/ml</brief_title>
    <official_title>A Randomized, Open-label, Controlled, Comparative Study of Efficacy and Safety of Dorzol Eye Drops, 20 mg/mL (JGL dd, Croatia) vs Trusopt® Eye Drops, 20 mg/mL (Merck Sharp &amp; Dohme, France) in Patients With Primary Open-angle Glaucoma</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Jadran Galenski laboratorij d.d.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Jadran Galenski laboratorij d.d.</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The goal of this study is to compare efficacy and safety of Dorzol 20 mg/mL Eye Drops&#xD;
        manufactured by JADRAN-GALENSKI LABORATORIJ d.d. (Croatia) aimed at lowering elevated IOP in&#xD;
        patients with ocular hypertension and primary open-angle glaucoma (POAG) versus TRUSOPT 20&#xD;
        MG/ML Eye Drops manufactured by Laboratoires Merck Sharp &amp; Dohme-Chibret, France. The main&#xD;
        questions it aims to answer are:&#xD;
  &#xD;
          -  if the efficacy of the investigational drug and the reference drug in patients with&#xD;
             ocular hypertension and primary open-angle glaucoma is equal;&#xD;
  &#xD;
          -  if the safety of the investigational drug and the reference drug in patients with ocular&#xD;
             hypertension and primary open-angle glaucoma is equal.&#xD;
  &#xD;
        A total of 118 participants were screened and randomized 1:1 to the investigational drug&#xD;
        (Dorzol) group or the reference drug (Trusopt) group. 59 patients were recruited in each&#xD;
        group.&#xD;
  &#xD;
        Researchers compared the investigational drug (Dorzol) group with the reference drug&#xD;
        (Trusopt) group to see if the efficacy and safety of the investigational drug and the&#xD;
        reference drug in patients with ocular hypertension and primary open-angle glaucoma are&#xD;
        equal.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Study Title:&#xD;
  &#xD;
        A randomized, open-label, controlled, comparative study of efficacy and safety of Dorzol eye&#xD;
        drops, 20 mg/mL, manufacturer: JADRAN - GALENSKI LABORATORIJ d.d., Croatia, vs. Trusopt® eye&#xD;
        drops, 20 mg/mL, manufacturer: Laboratoires Merck Sharp &amp; Dohme-Chibret, France, in patients&#xD;
        with primary open-angle glaucoma.&#xD;
  &#xD;
        Protocol No. DORZOL-10/2015, version No. 1.0 of 25.10.2015 RCT No. 629 of 07.09.2016&#xD;
        Investigators&#xD;
  &#xD;
          1. Abdulaeva Elmira Abdulaevna (Test facility No.4)&#xD;
  &#xD;
          2. Eryomina Alyona Victorovna (Test facility No.6)&#xD;
  &#xD;
          3. Lisitsyn Alexey Borisovich (Test facility No.7)&#xD;
  &#xD;
          4. Doga Alexander Victorovich (Test facility No.8) Test facilities No.4. State autonomous&#xD;
             healthcare institution 'Republican Clinical Ophthalmological Hospital of the Ministry of&#xD;
             Health of the Republic of Tatarstan', 420012, Republic of Tatarstan, Kazan, Butlerova&#xD;
             St., 14.&#xD;
  &#xD;
             No.6. Federal state autonomous institution 'Acad. S.N. Fyodorov Eye Microsurgery&#xD;
             Interbranch Science and Technology Complex', Ministry of Health of the Russian&#xD;
             Federation, 127486, Moscow, Beskudnikovsky Blvd., 59A.&#xD;
  &#xD;
             No.7. State healthcare institution of Yaroslavl region 'Clinical Hospital No. 8',&#xD;
             150030. Yaroslavl, Suzdalskoe Highway, 39.&#xD;
  &#xD;
             No.8. Federal state autonomous institution 'Acad. S.N. Fyodorov Eye Microsurgery&#xD;
             Interbranch Science and Technology Complex', Ministry of Health of the Russian&#xD;
             Federation, 127486, Moscow, Beskudnikovsky Blvd., 59A.&#xD;
  &#xD;
             Study period:&#xD;
  &#xD;
             First patient enrollment date: 5 April 2017 Study completion date: 1 September 2018&#xD;
             Phase III (a safety and efficacy study)&#xD;
  &#xD;
             Study objective:&#xD;
  &#xD;
             The study objective was to evaluate the efficacy and safety of Dorzol eye drops, 20&#xD;
             mg/mL, manufacturer: JADRAN - GALENSKI LABORATORIJ d.d., Croatia, designed to reduce&#xD;
             elevated intraocular pressure in patients with primary open-angle glaucoma (POAG), vs.&#xD;
             Trusopt® eye drops, 20 mg/mL, manufacturer: Laboratoires Merck Sharp &amp; Dohme-Chibret,&#xD;
             France.&#xD;
  &#xD;
             Study tasks:&#xD;
  &#xD;
               -  Prove noninferiority of the test vs. reference product in patients with primary&#xD;
                  open-angle glaucoma.&#xD;
  &#xD;
               -  Prove that the test product is as safe as the reference product in patients with&#xD;
                  primary open-angle glaucoma.&#xD;
  &#xD;
             Study design:&#xD;
  &#xD;
             A multicenter, prospective, open-label, randomized, comparative, controlled,&#xD;
             parallel-arm study evaluating the efficacy and safety in patients with a specific&#xD;
             disease.&#xD;
  &#xD;
             Study subjects: 118 patients (59 subjects in each group) with elevated intraocular&#xD;
             pressure induced by primary open-angle glaucoma (POAG), males and females in the age&#xD;
             bracket of 18 to 75 years conforming to the inclusion and exclusion criteria.&#xD;
  &#xD;
             Patients randomized: 118 Dropouts: 1 Per protocol population: 117 Safety population: 118&#xD;
  &#xD;
             Inclusion criteria:&#xD;
  &#xD;
               -  Females or males in the age bracket of 18 to 75 years.&#xD;
  &#xD;
               -  Established stage I and II primary open-angle glaucoma in one or both eyes.&#xD;
  &#xD;
               -  IOP = 21-27 mm Hg (by Goldmann applanation tonometry).&#xD;
  &#xD;
               -  Visual acuity 0.3 or better on the tested eye.&#xD;
  &#xD;
               -  Patients who have signed an informed consent to participate in the study.&#xD;
  &#xD;
               -  For females of child-bearing potential - a negative pregnancy test and consent to&#xD;
                  use reliable contraception methods throughout the study.&#xD;
  &#xD;
             Exclusion criteria:&#xD;
  &#xD;
               -  Contraindications or hypersensitivity to the active ingredient (dorzolamide) or&#xD;
                  excipients.&#xD;
  &#xD;
               -  The only eye.&#xD;
  &#xD;
               -  Visual acuity ˂ 0.3 after correction.&#xD;
  &#xD;
               -  An active infectious inflammatory process on the tested eye within 3 months prior&#xD;
                  to pre-study medical examination.&#xD;
  &#xD;
               -  Pronounced visual field defects (III and IV stage open-angle glaucoma).&#xD;
  &#xD;
               -  IOP ˃ 27 mm Hg or ˂ 21 mm Hg as at the IOP measuring at 10.00 a.m. (±1 h) in any of&#xD;
                  the eyes on the screening visit day.&#xD;
  &#xD;
               -  Closed or nearly closed anterior chamber angle (ACA) or history of acute angle&#xD;
                  close.&#xD;
  &#xD;
               -  Surgical and laser eye interventions over the last 3 months.&#xD;
  &#xD;
               -  Manifest ocular media opacification hindering the treatment efficacy evaluation.&#xD;
  &#xD;
               -  Other eye diseases that may affect dynamics of the parameters used for the&#xD;
                  treatment efficacy evaluation.&#xD;
  &#xD;
               -  Inflammatory conditions of the eye and appendages (blepharitis, conjunctivitis).&#xD;
  &#xD;
               -  Chronic kidney disease (creatinine clearance ˂ 30 mL/min).&#xD;
  &#xD;
               -  Hyperchloremic acidosis.&#xD;
  &#xD;
               -  Concomitant administration of oral carbonic anhydrase inhibitors.&#xD;
  &#xD;
               -  Children and adolescents under 18 years.&#xD;
  &#xD;
               -  The patient's participation in another clinical trial for the last 3 months.&#xD;
  &#xD;
               -  Any systemic or mental disorder/condition (unmanageable arterial hypertension,&#xD;
                  decompensated diabetes mellitus, severe renal impairment) or clinically relevant&#xD;
                  abnormal laboratory tests at screening that, in the Investigator's opinion, may put&#xD;
                  a patient to a significant risk, or compromise the study results, or appreciably&#xD;
                  affect the possibility for the patient to participate in the study.&#xD;
  &#xD;
               -  A patient who is unlikely to comply with the protocol requirements, e.g., is&#xD;
                  undisposed to cooperation, and is unlikely to complete the study.&#xD;
  &#xD;
               -  Females and males of reproductive age refusing to use efficacious contraception&#xD;
                  methods.&#xD;
  &#xD;
               -  Females during pregnancy and breastfeeding. Drug therapy type&#xD;
  &#xD;
             Test product:&#xD;
  &#xD;
             Trade name: Dorzol Active ingredient: dorzolamide Pharmaceutical form: eye drops Dosage:&#xD;
             20 mg/mL Posology and method of administration: Instillation into the conjunctival sac&#xD;
             of 1 drop 3 times daily for 12 weeks.&#xD;
  &#xD;
             Manufacturer: JADRAN - GALENSKI LABORATORIJ d.d., Croatia&#xD;
  &#xD;
             Reference product description and labeling:&#xD;
  &#xD;
             Trade name: Trusopt® Active ingredient: dorzolamide Pharmaceutical form: eye drops&#xD;
             Dosage: 20 mg/mL Posology and method of administration: 3 times daily Manufacturer:&#xD;
             Laboratoires Merck Sharp &amp; Dohme-Chibret, France Study duration: Screening: 7 days. The&#xD;
             comparison product treatment lasted for 12 weeks (84±2 days). Follow-up period: 7 days.&#xD;
             The overall study duration per patient did not exceed 99±2 days.&#xD;
  &#xD;
             The efficacy is established based on analysis of the parameters as follows:&#xD;
  &#xD;
             Primary endpoint&#xD;
  &#xD;
             • Mean IOP change from baseline.&#xD;
  &#xD;
             Secondary endpoints&#xD;
  &#xD;
               -  IOP reduction rate to the target level of ≤ 18 mm Hg.&#xD;
  &#xD;
               -  IOP reduction rate greater than 20%.&#xD;
  &#xD;
               -  IOP reduction rate greater than 30%. Safety evaluation&#xD;
  &#xD;
               -  Incidence of adverse events to a greater or lesser extent linked to the test or&#xD;
                  reference product, including those evaluated from laboratory test findings.&#xD;
  &#xD;
               -  Treatment safety is evaluated from recording adverse events via analysis of&#xD;
                  complaints and symptoms, evaluation and interpretation of the findings of&#xD;
                  instrumental monitoring (biomicroscopy, ophthalmoscopy, IOP measures, perimetry)&#xD;
                  and laboratory tests.&#xD;
  &#xD;
             Statistical analysis Statistical analysis was performed using Statsoft Statistica&#xD;
             Professional 13 and Microsoft Excel 2016 software.&#xD;
  &#xD;
             The Shapiro-Wilk test was used to evaluate the normality of distribution of quantitative&#xD;
             attributes. Parametric tests were used for testing statistical hypotheses for parameters&#xD;
             with the normal distribution, whereas nonparametric tests were used for parameters with&#xD;
             the variance of the distribution. Student's t-test and Mann-Whitney U test were used for&#xD;
             comparing the study groups in terms of quantitative attributes. The comparison of&#xD;
             intragroup parameters before and after treatment was performed using the dependent&#xD;
             samples t-test or the Wilcoxon test. The intragroup comparisons were also performed&#xD;
             using nonparametric repeated measures ANOVA (the Friedman test). Qualitative attributes&#xD;
             were analyzed using Pearson's χ2 test or Fisher's exact test (if the attribute incidence&#xD;
             rate in at least one subgroup was ≤ 5).&#xD;
  &#xD;
             Statistically significant are differences with p-values &lt; 0.05. Efficacy analysis of the&#xD;
             comparison products provides for a conclusion on&#xD;
  &#xD;
               -  Noninferiority of the test product Dorzol, eye drops (JADRAN - GALENSKI LABORATORIJ&#xD;
                  d.d., Croatia) vs. reference product Trusopt®, eye drops (Laboratoires Merck Sharp&#xD;
                  &amp; Dohme-Chibret, France) by the primary endpoint:&#xD;
  &#xD;
                    -  No statistically significant intergroup differences have been observed&#xD;
                       regarding a mean intraocular pressure change from baseline either in the&#xD;
                       treatment or control group (p = 0.1609; Mann-Whitney U test).&#xD;
  &#xD;
                    -  The efficacy differences between the test and reference product by the primary&#xD;
                       criterion do not exceed the noninferiority margin of 1.5 mm Hg.&#xD;
  &#xD;
             Intergroup efficacy comparisons of the comparison products by the secondary endpoints&#xD;
             have also been performed, with statistical significance of intergroup differences&#xD;
             evaluated for ITT and PP populations:&#xD;
  &#xD;
               -  ITT&#xD;
  &#xD;
                  o No statistically significant intergroup differences have been observed regarding&#xD;
                  the IOP reduction rate to the target level of ≤ 18 mm Hg either in the treatment or&#xD;
                  control group (p = 0.5727; Pearson's χ2 test), which is indicative of Dorzol&#xD;
                  noninferiority by this parameter vs. reference product.&#xD;
  &#xD;
                  o No statistically significant intergroup differences have been observed regarding&#xD;
                  the IOP reduction rate greater than 20% at visit 5 from baseline at visit 1&#xD;
                  pre-dose either in the treatment or control group (p = 0.5661; Pearson's χ2 test),&#xD;
                  which is indicative of Dorzol noninferiority by this parameter vs. reference&#xD;
                  product.&#xD;
  &#xD;
                  o No statistically significant intergroup differences have been observed regarding&#xD;
                  the IOP reduction rate greater than 30% at visit 5 from baseline at visit 1&#xD;
                  pre-dose either in the treatment or control group (p = 0.4524; Pearson's χ2 test),&#xD;
                  which is indicative of Dorzol noninferiority by this parameter vs. reference&#xD;
                  product.&#xD;
  &#xD;
               -  PP o No statistically significant intergroup differences have been observed&#xD;
                  regarding the IOP reduction rate to the target level of ≤ 18 mm Hg either in the&#xD;
                  treatment or control group (p = 0.5212; Pearson's χ2 test), which is indicative of&#xD;
                  Dorzol noninferiority by this parameter vs. reference product.&#xD;
  &#xD;
                  o No statistically significant intergroup differences have been observed regarding&#xD;
                  the IOP reduction rate greater than 20% at visit 5 from baseline at visit 1&#xD;
                  pre-dose either in the treatment or control group (p = 0.6494; Pearson's χ2 test),&#xD;
                  which is indicative of Dorzol noninferiority by this parameter vs. reference&#xD;
                  product.&#xD;
  &#xD;
                    -  No statistically significant intergroup differences have been observed&#xD;
                       regarding the IOP reduction rate greater than 30% at visit 5 from baseline at&#xD;
                       visit 1 pre-dose either in the treatment or control group (p = 0.4769;&#xD;
                       Pearson's χ2 test), which is indicative of Dorzol noninferiority by this&#xD;
                       parameter vs. reference product.&#xD;
  &#xD;
             The safety evaluation provided for the conclusions as follows:&#xD;
  &#xD;
               -  Analysis of these AEs is indicative of comparable safety of the test product:&#xD;
  &#xD;
                  o AE occurrence in the treatment group does not differ reliably from AE occurrence&#xD;
                  in the control group (p = 0.7058; Pearson's χ2 test).&#xD;
  &#xD;
                  o AE link to the test product was most characterized as 'probable'; there were no&#xD;
                  statistically significant intergroup differences by this parameter either (p =&#xD;
                  0,073).&#xD;
  &#xD;
                    -  AE severity was most characterized as mild; there were no statistically&#xD;
                       significant intergroup differences by this parameter either (p = 0.0863).&#xD;
  &#xD;
               -  Analysis of the patients' laboratory test findings has identified statistically&#xD;
                  reliable differences by certain parameters (hemoglobin, ESR, AST, ALT, urea, total&#xD;
                  bilirubin, total protein, urine specific gravity). However, these differences are&#xD;
                  linked to patients' personality traits.&#xD;
  &#xD;
             Thus, based on all criteria specified in the Clinical Trial Protocol, the test product&#xD;
             Dorzol and reference product Trusopt® demonstrate close efficacy and safety parameters.&#xD;
             There are no statistically significant intergroup differences by any efficacy criteria&#xD;
             tested. The efficacy differences between the test and reference product by the primary&#xD;
             criterion do not exceed the noninferiority margin of 1.5 mm Hg. The above-stated&#xD;
             provides for a conclusion on the test product Dorzol noninferiority vs. reference&#xD;
             product Trusopt®.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Completed</overall_status>
    <start_date type="Actual">April 5, 2017</start_date>
    <completion_date type="Actual">September 1, 2018</completion_date>
    <primary_completion_date type="Actual">April 5, 2017</primary_completion_date>
    <phase>Phase 3</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Mean IOP change from baseline</measure>
      <time_frame>12 weeks</time_frame>
      <description>Mean change in intraocular pressure (IOP) at visit 5 compared to baseline at visit 0</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>IOP reduction rate to the target level of ≤ 18 mm Hg</measure>
      <time_frame>12 weeks</time_frame>
      <description>Incidence of IOP reduction rate to the target level of ≤ 18 mm Hg (at visit 5)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>IOP reduction rate by more than 20%</measure>
      <time_frame>12 weeks</time_frame>
      <description>Incidence of IOP reduction rate by more than 20% (at visit 5)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>IOP reduction rate by more than 30%</measure>
      <time_frame>12 weeks</time_frame>
      <description>Incidence of IOP reduction rate by more than 30% (at visit 5)</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Actual">118</enrollment>
    <condition>Primary Open Angle Glaucoma of Both Eyes</condition>
    <arm_group>
      <arm_group_label>Patients with primary open-angle glaucoma receiving Dorzol 20 mg/ml</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Dorzol 20 mg/ml eye drops, dosing schedule t.i.d, 12 weeks</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Patients with primary open-angle glaucoma receiving Trusopt 20 mg/ml</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Trusopt 20 mg/ml eye drops, dosing schedule t.i.d, 12 weeks</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Dorzol 20 mg/ml</intervention_name>
      <description>dosing schedule t.i.d.</description>
      <arm_group_label>Patients with primary open-angle glaucoma receiving Dorzol 20 mg/ml</arm_group_label>
      <other_name>Dorzol</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Trusopt 20 mg/ml</intervention_name>
      <description>dosing schedule t.i.d.</description>
      <arm_group_label>Patients with primary open-angle glaucoma receiving Trusopt 20 mg/ml</arm_group_label>
      <other_name>Trusopt</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Females or males in the age bracket of 18 to 75 years.&#xD;
  &#xD;
            -  Established stage I and II primary open-angle glaucoma in one or both eyes.&#xD;
  &#xD;
            -  IOP = 21-27 mm Hg (by Goldmann applanation tonometry).&#xD;
  &#xD;
            -  Visual acuity 0.3 or better on the tested eye.&#xD;
  &#xD;
            -  Patients who have signed an informed consent to participate in the study.&#xD;
  &#xD;
            -  For females of child-bearing potential - a negative pregnancy test and consent to use&#xD;
               reliable contraception methods throughout the study.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Contraindications or hypersensitivity to the active ingredient (dorzolamide) or&#xD;
               excipients.&#xD;
  &#xD;
            -  The only eye.&#xD;
  &#xD;
            -  Visual acuity ˂ 0.3 after correction.&#xD;
  &#xD;
            -  An active infectious inflammatory process on the tested eye within 3 months prior to&#xD;
               pre-study medical examination.&#xD;
  &#xD;
            -  Pronounced visual field defects (III and IV stage open-angle glaucoma).&#xD;
  &#xD;
            -  IOP ˃ 27 mm Hg or ˂ 21 mm Hg as at the IOP measuring at 10.00 a.m. (±1 h) in any of&#xD;
               the eyes on the screening visit day.&#xD;
  &#xD;
            -  Closed or nearly closed anterior chamber angle (ACA) or history of acute angle close.&#xD;
  &#xD;
            -  Surgical and laser eye interventions over the last 3 months.&#xD;
  &#xD;
            -  Manifest ocular media opacification hindering the treatment efficacy evaluation.&#xD;
  &#xD;
            -  Other eye diseases that may affect dynamics of the parameters used for the treatment&#xD;
               efficacy evaluation.&#xD;
  &#xD;
            -  Inflammatory conditions of the eye and appendages (blepharitis, conjunctivitis).&#xD;
  &#xD;
            -  Chronic kidney disease (creatinine clearance ˂ 30 mL/min).&#xD;
  &#xD;
            -  Hyperchloremic acidosis.&#xD;
  &#xD;
            -  Concomitant administration of oral carbonic anhydrase inhibitors.&#xD;
  &#xD;
            -  Children and adolescents under 18 years.&#xD;
  &#xD;
            -  The patient's participation in another clinical trial for the last 3 months.&#xD;
  &#xD;
            -  Any systemic or mental disorder/condition (unmanageable arterial hypertension,&#xD;
               decompensated diabetes mellitus, severe renal impairment) or clinically relevant&#xD;
               abnormal laboratory tests at screening that, in the Investigator's opinion, may put a&#xD;
               patient to a significant risk, or compromise the study results, or appreciably affect&#xD;
               the possibility for the patient to participate in the study.&#xD;
  &#xD;
            -  A patient who is unlikely to comply with the protocol requirements, e.g., is&#xD;
               undisposed to cooperation, and is unlikely to complete the study.&#xD;
  &#xD;
            -  Females and males of reproductive age refusing to use efficacious contraception&#xD;
               methods.&#xD;
  &#xD;
            -  Females during pregnancy and breastfeeding.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Elmira Abdulaeva, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Republican Clinical Ophthalmological Hospital of the Ministry of Health of the Republic of Tatarstan</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>State autonomous healthcare institution 'Republican Clinical Ophthalmological Hospital of the Ministry of Health of the Republic of Tatarstan'</name>
        <address>
          <city>Kazan</city>
          <country>Russian Federation</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Russian Federation</country>
    </location_countries>
    <verification_date>April 2023</verification_date>
    <study_first_submitted>July 26, 2023</study_first_submitted>
    <study_first_submitted_qc>July 26, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 2, 2023</study_first_posted>
    <last_update_submitted>July 26, 2023</last_update_submitted>
    <last_update_submitted_qc>July 26, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 2, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Glaucoma</keyword>
    <keyword>Intraocular pressure</keyword>
    <keyword>Treatment</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>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Dorzolamide</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05973305
  org study id: DORZOL-10/2015
  nct id: NCT05973305
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this study is to compare efficacy and safety of Dorzol 20 mg/mL Eye Drops
        manufactured by JADRAN-GALENSKI LABORATORIJ d.d. (Croatia) aimed at lowering elevated IOP in
        patients with ocular hypertension and primary open-angle glaucoma (POAG) versus TRUSOPT 20
        MG/ML Eye Drops manufactured by Laboratoires Merck Sharp & Dohme-Chibret, France. The main
        questions it aims to answer are:
  
          -  if the efficacy of the investigational drug and the reference drug in patients with
             ocular hypertension and primary open-angle glaucoma is equal;
  
          -  if the safety of the investigational drug and the reference drug in patients with ocular
             hypertension and primary open-angle glaucoma is equal.
  
        A total of 118 participants were screened and randomized 1:1 to the investigational drug
        (Dorzol) group or the reference drug (Trusopt) group. 59 patients were recruited in each
        group.
  
        Researchers compared the investigational drug (Dorzol) group with the reference drug
        (Trusopt) group to see if the efficacy and safety of the investigational drug and the
        reference drug in patients with ocular hypertension and primary open-angle glaucoma are
        equal.
  Study Title:
  
        A randomized, open-label, controlled, comparative study of efficacy and safety of Dorzol eye
        drops, 20 mg/mL, manufacturer: JADRAN - GALENSKI LABORATORIJ d.d., Croatia, vs. Trusopt® eye
        drops, 20 mg/mL, manufacturer: Laboratoires Merck Sharp & Dohme-Chibret, France, in patients
        with primary open-angle glaucoma.
  
        Protocol No. DORZOL-10/2015, version No. 1.0 of 25.10.2015 RCT No. 629 of 07.09.2016
        Investigators
  
          1. Abdulaeva Elmira Abdulaevna (Test facility No.4)
  
          2. Eryomina Alyona Victorovna (Test facility No.6)
  
          3. Lisitsyn Alexey Borisovich (Test facility No.7)
  
          4. Doga Alexander Victorovich (Test facility No.8) Test facilities No.4. State autonomous
             healthcare institution 'Republican Clinical Ophthalmological Hospital of the Ministry of
             Health of the Republic of Tatarstan', 420012, Republic of Tatarstan, Kazan, Butlerova
             St., 14.
  
             No.6. Federal state autonomous institution 'Acad. S.N. Fyodorov Eye Microsurgery
             Interbranch Science and Technology Complex', Ministry of Health of the Russian
             Federation, 127486, Moscow, Beskudnikovsky Blvd., 59A.
  
             No.7. State healthcare institution of Yaroslavl region 'Clinical Hospital No. 8',
             150030. Yaroslavl, Suzdalskoe Highway, 39.
  
             No.8. Federal state autonomous institution 'Acad. S.N. Fyodorov Eye Microsurgery
             Interbranch Science and Technology Complex', Ministry of Health of the Russian
             Federation, 127486, Moscow, Beskudnikovsky Blvd., 59A.
  
             Study period:
  
             First patient enrollment date: 5 April 2017 Study completion date: 1 September 2018
             Phase III (a safety and efficacy study)
  
             Study objective:
  
             The study objective was to evaluate the efficacy and safety of Dorzol eye drops, 20
             mg/mL, manufacturer: JADRAN - GALENSKI LABORATORIJ d.d., Croatia, designed to reduce
             elevated intraocular pressure in patients with primary open-angle glaucoma (POAG), vs.
             Trusopt® eye drops, 20 mg/mL, manufacturer: Laboratoires Merck Sharp & Dohme-Chibret,
             France.
  
             Study tasks:
  
               -  Prove noninferiority of the test vs. reference product in patients with primary
                  open-angle glaucoma.
  
               -  Prove that the test product is as safe as the reference product in patients with
                  primary open-angle glaucoma.
  
             Study design:
  
             A multicenter, prospective, open-label, randomized, comparative, controlled,
             parallel-arm study evaluating the efficacy and safety in patients with a specific
             disease.
  
             Study subjects: 118 patients (59 subjects in each group) with elevated intraocular
             pressure induced by primary open-angle glaucoma (POAG), males and females in the age
             bracket of 18 to 75 years conforming to the inclusion and exclusion criteria.
  
             Patients randomized: 118 Dropouts: 1 Per protocol population: 117 Safety population: 118
  
             Inclusion criteria:
  
               -  Females or males in the age bracket of 18 to 75 years.
  
               -  Established stage I and II primary open-angle glaucoma in one or both eyes.
  
               -  IOP = 21-27 mm Hg (by Goldmann applanation tonometry).
  
               -  Visual acuity 0.3 or better on the tested eye.
  
               -  Patients who have signed an informed consent to participate in the study.
  
               -  For females of child-bearing potential - a negative pregnancy test and consent to
                  use reliable contraception methods throughout the study.
  
             Exclusion criteria:
  
               -  Contraindications or hypersensitivity to the active ingredient (dorzolamide) or
                  excipients.
  
               -  The only eye.
  
               -  Visual acuity ˂ 0.3 after correction.
  
               -  An active infectious inflammatory process on the tested eye within 3 months prior
                  to pre-study medical examination.
  
               -  Pronounced visual field defects (III and IV stage open-angle glaucoma).
  
               -  IOP ˃ 27 mm Hg or ˂ 21 mm Hg as at the IOP measuring at 10.00 a.m. (±1 h) in any of
                  the eyes on the screening visit day.
  
               -  Closed or nearly closed anterior chamber angle (ACA) or history of acute angle
                  close.
  
               -  Surgical and laser eye interventions over the last 3 months.
  
               -  Manifest ocular media opacification hindering the treatment efficacy evaluation.
  
               -  Other eye diseases that may affect dynamics of the parameters used for the
                  treatment efficacy evaluation.
  
               -  Inflammatory conditions of the eye and appendages (blepharitis, conjunctivitis).
  
               -  Chronic kidney disease (creatinine clearance ˂ 30 mL/min).
  
               -  Hyperchloremic acidosis.
  
               -  Concomitant administration of oral carbonic anhydrase inhibitors.
  
               -  Children and adolescents under 18 years.
  
               -  The patient's participation in another clinical trial for the last 3 months.
  
               -  Any systemic or mental disorder/condition (unmanageable arterial hypertension,
                  decompensated diabetes mellitus, severe renal impairment) or clinically relevant
                  abnormal laboratory tests at screening that, in the Investigator's opinion, may put
                  a patient to a significant risk, or compromise the study results, or appreciably
                  affect the possibility for the patient to participate in the study.
  
               -  A patient who is unlikely to comply with the protocol requirements, e.g., is
                  undisposed to cooperation, and is unlikely to complete the study.
  
               -  Females and males of reproductive age refusing to use efficacious contraception
                  methods.
  
               -  Females during pregnancy and breastfeeding. Drug therapy type
  
             Test product:
  
             Trade name: Dorzol Active ingredient: dorzolamide Pharmaceutical form: eye drops Dosage:
             20 mg/mL Posology and method of administration: Instillation into the conjunctival sac
             of 1 drop 3 times daily for 12 weeks.
  
             Manufacturer: JADRAN - GALENSKI LABORATORIJ d.d., Croatia
  
             Reference product description and labeling:
  
             Trade name: Trusopt® Active ingredient: dorzolamide Pharmaceutical form: eye drops
             Dosage: 20 mg/mL Posology and method of administration: 3 times daily Manufacturer:
             Laboratoires Merck Sharp & Dohme-Chibret, France Study duration: Screening: 7 days. The
             comparison product treatment lasted for 12 weeks (84±2 days). Follow-up period: 7 days.
             The overall study duration per patient did not exceed 99±2 days.
  
             The efficacy is established based on analysis of the parameters as follows:
  
             Primary endpoint
  
             • Mean IOP change from baseline.
  
             Secondary endpoints
  
               -  IOP reduction rate to the target level of ≤ 18 mm Hg.
  
               -  IOP reduction rate greater than 20%.
  
               -  IOP reduction rate greater than 30%. Safety evaluation
  
               -  Incidence of adverse events to a greater or lesser extent linked to the test or
                  reference product, including those evaluated from laboratory test findings.
  
               -  Treatment safety is evaluated from recording adverse events via analysis of
                  complaints and symptoms, evaluation and interpretation of the findings of
                  instrumental monitoring (biomicroscopy, ophthalmoscopy, IOP measures, perimetry)
                  and laboratory tests.
  
             Statistical analysis Statistical analysis was performed using Statsoft Statistica
             Professional 13 and Microsoft Excel 2016 software.
  
             The Shapiro-Wilk test was used to evaluate the normality of distribution of quantitative
             attributes. Parametric tests were used for testing statistical hypotheses for parameters
             with the normal distribution, whereas nonparametric tests were used for parameters with
             the variance of the distribution. Student's t-test and Mann-Whitney U test were used for
             comparing the study groups in terms of quantitative attributes. The comparison of
             intragroup parameters before and after treatment was performed using the dependent
             samples t-test or the Wilcoxon test. The intragroup comparisons were also performed
             using nonparametric repeated measures ANOVA (the Friedman test). Qualitative attributes
             were analyzed using Pearson's χ2 test or Fisher's exact test (if the attribute incidence
             rate in at least one subgroup was ≤ 5).
  
             Statistically significant are differences with p-values < 0.05. Efficacy analysis of the
             comparison products provides for a conclusion on
  
               -  Noninferiority of the test product Dorzol, eye drops (JADRAN - GALENSKI LABORATORIJ
                  d.d., Croatia) vs. reference product Trusopt®, eye drops (Laboratoires Merck Sharp
                  & Dohme-Chibret, France) by the primary endpoint:
  
                    -  No statistically significant intergroup differences have been observed
                       regarding a mean intraocular pressure change from baseline either in the
                       treatment or control group (p = 0.1609; Mann-Whitney U test).
  
                    -  The efficacy differences between the test and reference product by the primary
                       criterion do not exceed the noninferiority margin of 1.5 mm Hg.
  
             Intergroup efficacy comparisons of the comparison products by the secondary endpoints
             have also been performed, with statistical significance of intergroup differences
             evaluated for ITT and PP populations:
  
               -  ITT
  
                  o No statistically significant intergroup differences have been observed regarding
                  the IOP reduction rate to the target level of ≤ 18 mm Hg either in the treatment or
                  control group (p = 0.5727; Pearson's χ2 test), which is indicative of Dorzol
                  noninferiority by this parameter vs. reference product.
  
                  o No statistically significant intergroup differences have been observed regarding
                  the IOP reduction rate greater than 20% at visit 5 from baseline at visit 1
                  pre-dose either in the treatment or control group (p = 0.5661; Pearson's χ2 test),
                  which is indicative of Dorzol noninferiority by this parameter vs. reference
                  product.
  
                  o No statistically significant intergroup differences have been observed regarding
                  the IOP reduction rate greater than 30% at visit 5 from baseline at visit 1
                  pre-dose either in the treatment or control group (p = 0.4524; Pearson's χ2 test),
                  which is indicative of Dorzol noninferiority by this parameter vs. reference
                  product.
  
               -  PP o No statistically significant intergroup differences have been observed
                  regarding the IOP reduction rate to the target level of ≤ 18 mm Hg either in the
                  treatment or control group (p = 0.5212; Pearson's χ2 test), which is indicative of
                  Dorzol noninferiority by this parameter vs. reference product.
  
                  o No statistically significant intergroup differences have been observed regarding
                  the IOP reduction rate greater than 20% at visit 5 from baseline at visit 1
                  pre-dose either in the treatment or control group (p = 0.6494; Pearson's χ2 test),
                  which is indicative of Dorzol noninferiority by this parameter vs. reference
                  product.
  
                    -  No statistically significant intergroup differences have been observed
                       regarding the IOP reduction rate greater than 30% at visit 5 from baseline at
                       visit 1 pre-dose either in the treatment or control group (p = 0.4769;
                       Pearson's χ2 test), which is indicative of Dorzol noninferiority by this
                       parameter vs. reference product.
  
             The safety evaluation provided for the conclusions as follows:
  
               -  Analysis of these AEs is indicative of comparable safety of the test product:
  
                  o AE occurrence in the treatment group does not differ reliably from AE occurrence
                  in the control group (p = 0.7058; Pearson's χ2 test).
  
                  o AE link to the test product was most characterized as 'probable'; there were no
                  statistically significant intergroup differences by this parameter either (p =
                  0,073).
  
                    -  AE severity was most characterized as mild; there were no statistically
                       significant intergroup differences by this parameter either (p = 0.0863).
  
               -  Analysis of the patients' laboratory test findings has identified statistically
                  reliable differences by certain parameters (hemoglobin, ESR, AST, ALT, urea, total
                  bilirubin, total protein, urine specific gravity). However, these differences are
                  linked to patients' personality traits.
  
             Thus, based on all criteria specified in the Clinical Trial Protocol, the test product
             Dorzol and reference product Trusopt® demonstrate close efficacy and safety parameters.
             There are no statistically significant intergroup differences by any efficacy criteria
             tested. The efficacy differences between the test and reference product by the primary
             criterion do not exceed the noninferiority margin of 1.5 mm Hg. The above-stated
             provides for a conclusion on the test product Dorzol noninferiority vs. reference
             product Trusopt®.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Mean IOP change from baseline
  time frame: 12 weeks
  description: Mean change in intraocular pressure (IOP) at visit 5 compared to baseline at visit 0
  measure: IOP reduction rate to the target level of ≤ 18 mm Hg
  time frame: 12 weeks
  description: Incidence of IOP reduction rate to the target level of ≤ 18 mm Hg (at visit 5)
  measure: IOP reduction rate by more than 20%
  time frame: 12 weeks
  description: Incidence of IOP reduction rate by more than 20% (at visit 5)
  measure: IOP reduction rate by more than 30%
  time frame: 12 weeks
  description: Incidence of IOP reduction rate by more than 30% (at visit 5)
  arm group label: Patients with primary open-angle glaucoma receiving Dorzol 20 mg/ml
  arm group type: Experimental
  description: Dorzol 20 mg/ml eye drops, dosing schedule t.i.d, 12 weeks
  arm group label: Patients with primary open-angle glaucoma receiving Trusopt 20 mg/ml
  arm group type: Active Comparator
  description: Trusopt 20 mg/ml eye drops, dosing schedule t.i.d, 12 weeks
  intervention type: Drug
  intervention name: Dorzol 20 mg/ml
  description: dosing schedule t.i.d.
  arm group label: Patients with primary open-angle glaucoma receiving Dorzol 20 mg/ml
  other name: Dorzol
  intervention type: Drug
  intervention name: Trusopt 20 mg/ml
  description: dosing schedule t.i.d.
  arm group label: Patients with primary open-angle glaucoma receiving Trusopt 20 mg/ml
  other name: Trusopt
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Elmira Abdulaeva, PhD
  role: Principal Investigator
  affiliation: Republican Clinical Ophthalmological Hospital of the Ministry of Health of the Republic of Tatarstan
  facility: 
  country: Russian Federation
  responsible party type: Sponsor
  mesh term: Glaucoma
  mesh term: Glaucoma, Open-Angle
  mesh term: Dorzolamide
  sharing ipd: No