<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/NCT03804268</url>
  </required_header>
  <id_info>
    <org_study_id>1883-301-013</org_study_id>
    <nct_id>NCT03804268</nct_id>
  </id_info>
  <brief_title>Efficacy Study of Pilocarpine HCl Ophthalmic Solution (AGN-190584) in Participants With Presbyopia</brief_title>
  <acronym>GEMINI 1</acronym>
  <official_title>A Phase 3, Multicenter, Double-Masked, Randomized, Vehicle-Controlled, Parallel-Group Study Evaluating the Safety and Efficacy of AGN-190584 in Participants With Presbyopia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Allergan</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Allergan</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A study to evaluate the efficacy, safety, and pharmacokinetics of pilocarpine hydrochloride&#xD;
      (HCl) ophthalmic solution (AGN-190584) when administered bilaterally, once daily for 30 days&#xD;
      in participants with presbyopia.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 21, 2018</start_date>
  <completion_date type="Actual">October 31, 2019</completion_date>
  <primary_completion_date type="Actual">October 31, 2019</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular Distance-Corrected Near Visual Acuity (DCNVA) at Day 30, Hour 3</measure>
    <time_frame>Baseline (Day 1) to Day 30 (Hour 3)</time_frame>
    <description>Visual acuity for near (40 centimeters (cm)) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 candelas per square meter (cd/m^2) measured at the target. Percentage of participants with 3 lines or more improvement from Baseline in mesopic, high-contrast DCNVA are reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular Distance-Corrected Near Visual Acuity (DCNVA) at Day 30, Hour 6</measure>
    <time_frame>Baseline (Day 1) to Day 30 (Hour 6)</time_frame>
    <description>Visual acuity for near (40 cm) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 candelas per square meter measured at the target. Percentage of participants with 3 lines or more improvement from Baseline in mesopic, high-contrast DCNVA are reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Gaining 3-lines or More in Mesopic, High-contrast, Binocular, DCNVA at Day 30, Hour 8</measure>
    <time_frame>Baseline (Day 1) to Day 30 (Hour 8)</time_frame>
    <description>Visual acuity for near (40 cm) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 candelas per square meter measured at the target. Percentage of participants with 3 lines or more improvement from Baseline in mesopic, high-contrast DCNVA are reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Mesopic, High-contrast, Binocular DCNVA Letters at Day 30, Hour 0.5</measure>
    <time_frame>Baseline (Day 1) to Day 30 (Hour 0.5)</time_frame>
    <description>Visual acuity for near (40 cm) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 cd/m^2 measured at the target. A positive change from Baseline indicates improvement in visual acuity. Mixed effect model for repeated measures (MMRM) was used for analyses.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Achieving 20/40 or Better in Photopic, High-contrast, Binocular, DCNVA at Day 30, Hour 1</measure>
    <time_frame>Day 30 (Hour 1)</time_frame>
    <description>Visual acuity for near (40 cm) target was measured in photopic conditions using an eye chart. Photopic condition was defined as high lighting ≥80 cd/m^2 measured at the target. Percentage of participants achieving 20/40 or better in photopic, high-contrast, binocular, DCNVA are reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Mesopic Near Vision Presbyopia Task-based Questionnaire (NVPTQ) Performance Score at Day 30, Hour 3</measure>
    <time_frame>Baseline (Day 1) to Day 30 (Hour 3)</time_frame>
    <description>NVPTQ had 12 questions on 4 reading tasks(reading a paragraph from book, excerpts from an article in newspaper, portion of a nutrition label, and a section from restaurant menu). Participants completed specific reading tasks under mesopic conditions without any near-vision correction and answered 3 questions for each task, rating their vision-related reading ability as 0=I could not read any text due to problems seeing up close,1=poor,2=fair,3=good,4=very good,5=excellent;impact of squinting on performance as 0=No,I did not squint, 1=Yes,squinting helped me read some/all text, 2=Yes,but I still could not read any of the text; and satisfaction as 0=very dissatisfied to 4=very satisfied. The score based on vision related ability and impact of squinting=(Book testlet+Newspaper testlet+Menu testlet+Nutrition Label testlet)/(testlets with non-missing responses), total possible score of 0-5. Higher scores=better outcomes;positive change from Baseline=improved performance(reading ability).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Photopic, High-contrast, Binocular Distance-corrected Intermediate Visual Acuity (DCIVA) Letters at Day 30, Hour 3</measure>
    <time_frame>Baseline (Day 1) to Day 30 (Hour 3)</time_frame>
    <description>Visual acuity for intermediate (66 cm) target was measured in photopic conditions using an eye chart. Photopic condition was defined as high lighting ≥80 cd/m^2 measured at the target. A positive change from Baseline indicates improvement in visual acuity. MMRM was used for analyses.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Gaining 3-lines or More in Mesopic, High-contrast, Binocular, DCNVA at Day 30, Hour 10</measure>
    <time_frame>Baseline (Day1) to Day 30 (Hour 10)</time_frame>
    <description>Visual acuity for near (40cm) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 cd/m^2measured at the target. Percentage of participants with 3 lines or more improvement from Baseline in mesopic, high-contrast, binocular DCNVA are reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Mesopic, High-contrast, Binocular DCNVA Letters at Day 30, Hour 0.25</measure>
    <time_frame>Baseline (Day 1) to Day 30 (Hour 0.25)</time_frame>
    <description>Visual acuity for near (40 cm) target was measured in mesopic conditions. Mesopic condition was defined as low lighting 3.2 to 3.5 cd/m^2 measured at the target. A positive change from Baseline indicates improvement in visual acuity. MMRM was used for analyses.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Achieving 20/40 or Better in Photopic, High-contrast, Binocular, DCNVA at Day 30, Hour 3</measure>
    <time_frame>Day 30 (Hour 3)</time_frame>
    <description>Visual acuity for near (40 cm) target was measured in mesopic conditions using an eye chart. Photopic condition was defined as high lighting ≥80 cd/m^2 measured at the target. Percentage of participants achieving 20/40 or better in photopic, high-contrast, binocular, DCNVA are reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Mesopic NVPTQ Satisfaction Score at Day 30, Hour 3</measure>
    <time_frame>Baseline (Day 1) to Day 30 (Hour 3)</time_frame>
    <description>NVPTQ had 12 questions on 4 reading tasks(reading a paragraph from book, excerpts from an article in newspaper, portion of a nutrition label, and a section from restaurant menu). Participants completed specific reading tasks under mesopic conditions without any near-vision correction and answered 3 questions for each task, rating their vision-related reading ability as 0=I could not read any text due to problems seeing up close to 5=excellent; impact of squinting on performance as 0=No, I did not squint, 1=Yes, squinting helped me read some/all text, 2=Yes, but I still could not read any of the text; and satisfaction as 0=very dissatisfied,1=dissatisfied,2=neither satisfied nor dissatisfied,3=satisfied, 4=very satisfied. The score based on satisfaction items=(Book testlet+Newspaper testlet+Menu testlet+Nutrition Label testlet)/(testlets with non-missing responses) for a total possible score of 0 to 4. Higher scores=better outcomes; a positive change from Baseline=higher satisfaction.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Presbyopia Impact and Coping Questionnaire (PICQ) Coping Score at Day 30, Hour 3</measure>
    <time_frame>Baseline (Day 1) to Day 30 (Hour 3)</time_frame>
    <description>PICQ=20 questions about impact experienced by participants due to their problems over past 7 days.PICQ Coping domain had 8 items: 1:Normal-sized text,2:Small-sized text,3:Information on a computer,4:Information on a cell phone,5:Increase font size,6:Use glasses to read close,12:Hold reading materials farther out/closer,13:Squint to read. Each item had response categories:0=never to 4=all the time. Items 3, 4, 5, and 6 had additional response categories with values of 9/10 to indicate the question is not applicable to participant and were assigned missing values.PICQ Coping Score:(Item 1,2 Testlet+Item 3,4 Testlet+Item 5+Item 6+Item 12+Item 13)/non-missing responses to the 6 components of coping score where Items 1,2 Testlet=(Item1+Item2)/non-missing responses to Items 1,2;Items 3,4 Testlet=(Item3+Item4)/non-missing responses to Items 3, 4. Score ranges:0=to least amount of coping to 4=greatest amount of coping. Higher scores=poorer outcome; a negative change from Baseline=improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in PICQ Impact Score at Day 30, Hour 3</measure>
    <time_frame>Baseline (Day 1) to Day 30 (Hour 3)</time_frame>
    <description>PICQ had 20 questions about impact experienced by participants due to their problems seeing up over past 7 days. PICQ Impact domain had 6 items: Item 9:Rely on others,15:rest eyes,16:Feel older,17:Feel self-conscious,19:Take longer to complete a task,20:Inconvenient. First 5 impacts items included response categories: 0=never to 4=all the time. Item 20 had response categories: 0=not at all to 4=extremely. Item 9 included an additional response category with a value of 9 to indicate question was not applicable to participant and the responses were assigned missing values. PICQ Impacts Score=[(Item9+Item15+Items16,17Testlet+Item19+Item20)/(nonmissing responses to 5 components of impacts score)] where Items 16,17 Testlet=(Item16+Item17)/non-missing responses to Items 16 and 17. PICQ Impact score ranges from 0 to 4; with 0=least amount of impacts to 4=greatest amount of impacts. Higher scores correspond to poorer outcomes. A negative change from Baseline=improvement.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">323</enrollment>
  <condition>Presbyopia</condition>
  <arm_group>
    <arm_group_label>Vehicle</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants received one drop of vehicle in each eye, once daily, for up to 30 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Pilocarpine HCl Ophthalmic Solution</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Vehicle</intervention_name>
    <description>Vehicle, one drop in each eye, once daily, for up to 30 days.</description>
    <arm_group_label>Vehicle</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pilocarpine HCl Ophthalmic Solution</intervention_name>
    <description>Pilocarpine HCl ophthalmic solution 1.25%, one drop in each eye, once daily, for up to 30 days.</description>
    <arm_group_label>Pilocarpine HCl Ophthalmic Solution</arm_group_label>
    <other_name>AGN-190584</other_name>
    <other_name>VUITY</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - Subjective complaints of poor near vision that impact activities of daily living&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of cataract surgery, phakic intraocular lens surgery, corneal inlay surgery,&#xD;
             radial keratotomy, or any intraocular surgery&#xD;
&#xD;
          -  Use of any topical ophthalmic medications, including artificial tears other than the&#xD;
             study medications during the study&#xD;
&#xD;
          -  Use of temporary or permanent punctal plugs or history of punctal cautery in one or&#xD;
             both eyes&#xD;
&#xD;
          -  Corneal abnormalities (including keratoconus, corneal scar, Fuchs' endothelial&#xD;
             dystrophy, guttata, or edema) in either eye that are likely to interfere with visual&#xD;
             acuity&#xD;
&#xD;
          -  Narrow iridocorneal angles (Shaffer grade ≤2 or lower on gonioscopy examination),&#xD;
             history of angle-closure glaucoma, or previous iridotomy&#xD;
&#xD;
          -  Diagnosis of any type of glaucoma or ocular hypertension&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Eleonora Safyan</last_name>
    <role>Study Director</role>
    <affiliation>Allergan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Arizona Eye Center</name>
      <address>
        <city>Chandler</city>
        <state>Arizona</state>
        <zip>85224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Schwartz Laser Eye Center</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85260</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Assil Eye Institute</name>
      <address>
        <city>Beverly Hills</city>
        <state>California</state>
        <zip>90210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>American Institute of Research</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90017</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eye Research Foundation</name>
      <address>
        <city>Newport Beach</city>
        <state>California</state>
        <zip>92663</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Martel Eye Medical Group</name>
      <address>
        <city>Rancho Cordova</city>
        <state>California</state>
        <zip>95670</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Grutzmacher &amp; Lewis, A Medical Corporation DBA Sacramento Eye Consultants</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95815</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Haas Vision Center</name>
      <address>
        <city>Colorado Springs</city>
        <state>Colorado</state>
        <zip>80919</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Danbury Eye Physicians and Surgeons P.C.</name>
      <address>
        <city>Danbury</city>
        <state>Connecticut</state>
        <zip>06810</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Eye Associates</name>
      <address>
        <city>Bradenton</city>
        <state>Florida</state>
        <zip>34209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bruce Segal, MD</name>
      <address>
        <city>Delray Beach</city>
        <state>Florida</state>
        <zip>33484</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Direct Helpers Research Center</name>
      <address>
        <city>Hialeah</city>
        <state>Florida</state>
        <zip>33012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Centers of America</name>
      <address>
        <city>Hollywood</city>
        <state>Florida</state>
        <zip>33024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Eye Associates</name>
      <address>
        <city>Melbourne</city>
        <state>Florida</state>
        <zip>32901</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>USF Eye Institute</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Price Vision Group</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46260</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sabates Eye Centers</name>
      <address>
        <city>Leawood</city>
        <state>Kansas</state>
        <zip>66211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Eye Care Institute</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seidenberg Protzko Eye Associates</name>
      <address>
        <city>Havre De Grace</city>
        <state>Maryland</state>
        <zip>21078</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tauber Eye Center</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alterman, Modi &amp; Wolter</name>
      <address>
        <city>Poughkeepsie</city>
        <state>New York</state>
        <zip>12603</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rochester Ophthalmological Group, PC</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14618</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mundorf Eye Center</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ohio State University</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>EyeCare Professionals DWA Insight Research Clinic, LLC</name>
      <address>
        <city>Powell</city>
        <state>Ohio</state>
        <zip>43065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Devers Eye Institute</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Scott &amp; Christie and Associates, PC</name>
      <address>
        <city>Cranberry Township</city>
        <state>Pennsylvania</state>
        <zip>16066</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Black Hills Regional Eye Institute</name>
      <address>
        <city>Rapid City</city>
        <state>South Dakota</state>
        <zip>57701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vance Thompson Vision</name>
      <address>
        <city>Sioux Falls</city>
        <state>South Dakota</state>
        <zip>57108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southern College of Optometry</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nashville Vision Associates</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hill Country Eye Center</name>
      <address>
        <city>Cedar Park</city>
        <state>Texas</state>
        <zip>78613</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Key-Whitman Eye Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75243</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PNV Clinical Research LLC</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>R and R Eye Research, LLC</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hoopes, Durrie, Rivera Research</name>
      <address>
        <city>Draper</city>
        <state>Utah</state>
        <zip>84020</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>January 11, 2019</study_first_submitted>
  <study_first_submitted_qc>January 11, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 15, 2019</study_first_posted>
  <results_first_submitted>November 27, 2021</results_first_submitted>
  <results_first_submitted_qc>November 27, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">December 28, 2021</results_first_posted>
  <disposition_first_submitted>October 30, 2020</disposition_first_submitted>
  <disposition_first_submitted_qc>October 30, 2020</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">November 2, 2020</disposition_first_posted>
  <last_update_submitted>November 27, 2021</last_update_submitted>
  <last_update_submitted_qc>November 27, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 28, 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>Presbyopia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ophthalmic Solutions</mesh_term>
    <mesh_term>Pilocarpine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <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>December 5, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/68/NCT03804268/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>January 30, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/68/NCT03804268/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Vehicle</title>
          <description>Participants received one drop of vehicle in each eye, once daily, for up to 30 days.</description>
        </group>
        <group group_id="P2">
          <title>Pilocarpine HCl Ophthalmic Solution</title>
          <description>Participants received one drop of pilocarpine hydrochloride (HCl) ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="160"/>
                <participants group_id="P2" count="163"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="153"/>
                <participants group_id="P2" count="161"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </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>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Intent-to-treat (ITT) Population included all randomized participants.</population>
      <group_list>
        <group group_id="B1">
          <title>Vehicle</title>
          <description>Participants received one drop of vehicle in each eye, once daily, for up to 30 days.</description>
        </group>
        <group group_id="B2">
          <title>Pilocarpine HCl Ophthalmic Solution</title>
          <description>Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.</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="160"/>
            <count group_id="B2" value="163"/>
            <count group_id="B3" value="323"/>
          </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="49.7" spread="3.23"/>
                    <measurement group_id="B2" value="49.5" spread="3.81"/>
                    <measurement group_id="B3" value="49.6" spread="3.53"/>
                  </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="122"/>
                    <measurement group_id="B2" value="113"/>
                    <measurement group_id="B3" value="235"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="38"/>
                    <measurement group_id="B2" value="50"/>
                    <measurement group_id="B3" value="88"/>
                  </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="26"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="57"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="134"/>
                    <measurement group_id="B2" value="132"/>
                    <measurement group_id="B3" value="266"/>
                  </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="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </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="12"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="144"/>
                    <measurement group_id="B2" value="148"/>
                    <measurement group_id="B3" value="292"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </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 Gaining 3 Lines or More in Mesopic, High-contrast, Binocular Distance-Corrected Near Visual Acuity (DCNVA) at Day 30, Hour 3</title>
        <description>Visual acuity for near (40 centimeters (cm)) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 candelas per square meter (cd/m^2) measured at the target. Percentage of participants with 3 lines or more improvement from Baseline in mesopic, high-contrast DCNVA are reported.</description>
        <time_frame>Baseline (Day 1) to Day 30 (Hour 3)</time_frame>
        <population>Intent-to-treat (ITT) Population included all randomized participants. Missing data was imputed as non-responders.</population>
        <group_list>
          <group group_id="O1">
            <title>Vehicle</title>
            <description>Participants received one drop of vehicle in each eye, once daily, for up to 30 days.</description>
          </group>
          <group group_id="O2">
            <title>Pilocarpine HCl Ophthalmic Solution</title>
            <description>Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular Distance-Corrected Near Visual Acuity (DCNVA) at Day 30, Hour 3</title>
          <description>Visual acuity for near (40 centimeters (cm)) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 candelas per square meter (cd/m^2) measured at the target. Percentage of participants with 3 lines or more improvement from Baseline in mesopic, high-contrast DCNVA are reported.</description>
          <population>Intent-to-treat (ITT) Population included all randomized participants. Missing data was imputed as non-responders.</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="160"/>
                <count group_id="O2" value="163"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.1"/>
                    <measurement group_id="O2" value="30.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>P-value was adjusted for multiplicity control.</p_value_desc>
            <method>Chi-squared</method>
            <param_type>Percentage Difference</param_type>
            <param_value>22.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>14.3</ci_lower_limit>
            <ci_upper_limit>30.8</ci_upper_limit>
            <estimate_desc>Analysis was done using Chi-square test. 95% confidence interval for the percentage differences was calculated based on the normal approximation based on pooled variance without continuity correction.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular Distance-Corrected Near Visual Acuity (DCNVA) at Day 30, Hour 6</title>
        <description>Visual acuity for near (40 cm) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 candelas per square meter measured at the target. Percentage of participants with 3 lines or more improvement from Baseline in mesopic, high-contrast DCNVA are reported.</description>
        <time_frame>Baseline (Day 1) to Day 30 (Hour 6)</time_frame>
        <population>ITT Population included all randomized participants. Missing data was imputed as non-responders.</population>
        <group_list>
          <group group_id="O1">
            <title>Vehicle</title>
            <description>Participants received one drop of vehicle in each eye, once daily, for up to 30 days.</description>
          </group>
          <group group_id="O2">
            <title>Pilocarpine HCl Ophthalmic Solution</title>
            <description>Participants received one drop of pilocarpine HCl ophthalmic solution1.25% in each eye, once daily, for up to 30 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular Distance-Corrected Near Visual Acuity (DCNVA) at Day 30, Hour 6</title>
          <description>Visual acuity for near (40 cm) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 candelas per square meter measured at the target. Percentage of participants with 3 lines or more improvement from Baseline in mesopic, high-contrast DCNVA are reported.</description>
          <population>ITT Population included all randomized participants. Missing data was imputed as non-responders.</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="160"/>
                <count group_id="O2" value="163"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.8"/>
                    <measurement group_id="O2" value="18.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0114</p_value>
            <p_value_desc>P-value was adjusted for multiplicity control.</p_value_desc>
            <method>Chi-squared</method>
            <param_type>Percentage Difference</param_type>
            <param_value>9.7</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>2.3</ci_lower_limit>
            <ci_upper_limit>17.0</ci_upper_limit>
            <estimate_desc>Analysis was done using Chi-square test. 95% confidence interval for the percentage differences was calculated based on the normal approximation based on pooled variance without continuity correction.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Gaining 3-lines or More in Mesopic, High-contrast, Binocular, DCNVA at Day 30, Hour 8</title>
        <description>Visual acuity for near (40 cm) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 candelas per square meter measured at the target. Percentage of participants with 3 lines or more improvement from Baseline in mesopic, high-contrast DCNVA are reported.</description>
        <time_frame>Baseline (Day 1) to Day 30 (Hour 8)</time_frame>
        <population>ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses at Baseline and the timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Vehicle</title>
            <description>Participants received one drop of vehicle in each eye, once daily, for up to 30 days.</description>
          </group>
          <group group_id="O2">
            <title>Pilocarpine HCl Ophthalmic Solution</title>
            <description>Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Gaining 3-lines or More in Mesopic, High-contrast, Binocular, DCNVA at Day 30, Hour 8</title>
          <description>Visual acuity for near (40 cm) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 candelas per square meter measured at the target. Percentage of participants with 3 lines or more improvement from Baseline in mesopic, high-contrast DCNVA are reported.</description>
          <population>ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses at Baseline and the timepoint.</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="153"/>
                <count group_id="O2" value="161"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.5"/>
                    <measurement group_id="O2" value="10.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>1.0000</p_value>
            <p_value_desc>P-value was adjusted for multiplicity control.</p_value_desc>
            <method>Chi-squared</method>
            <param_type>Percentage Difference</param_type>
            <param_value>2.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.4</ci_lower_limit>
            <ci_upper_limit>8.5</ci_upper_limit>
            <estimate_desc>Analysis was done using Chi-square test. 95% confidence interval for the percentage differences was calculated based on the normal approximation based on pooled variance without continuity correction.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Mesopic, High-contrast, Binocular DCNVA Letters at Day 30, Hour 0.5</title>
        <description>Visual acuity for near (40 cm) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 cd/m^2 measured at the target. A positive change from Baseline indicates improvement in visual acuity. Mixed effect model for repeated measures (MMRM) was used for analyses.</description>
        <time_frame>Baseline (Day 1) to Day 30 (Hour 0.5)</time_frame>
        <population>ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>Vehicle</title>
            <description>Participants received one drop of vehicle in each eye, once daily, for up to 30 days.</description>
          </group>
          <group group_id="O2">
            <title>Pilocarpine HCl Ophthalmic Solution</title>
            <description>Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Mesopic, High-contrast, Binocular DCNVA Letters at Day 30, Hour 0.5</title>
          <description>Visual acuity for near (40 cm) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 cd/m^2 measured at the target. A positive change from Baseline indicates improvement in visual acuity. Mixed effect model for repeated measures (MMRM) was used for analyses.</description>
          <population>ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses.</population>
          <units>letters read correctly</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="153"/>
                <count group_id="O2" value="158"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.2" spread="0.55"/>
                    <measurement group_id="O2" value="9.3" spread="0.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0114</p_value>
            <p_value_desc>MMRM with fixed effects: study intervention group,visit,visit by study intervention group interaction,age group,Baseline binocular DCNVA severity,iris color,emmetrope/non-emmetrope, Baseline value, and Baseline value by visit interaction was used.</p_value_desc>
            <method>MMRM</method>
            <method_desc>P-value was adjusted for multiplicity control.</method_desc>
            <param_type>Least Square (LS) Mean Difference</param_type>
            <param_value>5.1</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.72</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>3.7</ci_lower_limit>
            <ci_upper_limit>6.5</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Achieving 20/40 or Better in Photopic, High-contrast, Binocular, DCNVA at Day 30, Hour 1</title>
        <description>Visual acuity for near (40 cm) target was measured in photopic conditions using an eye chart. Photopic condition was defined as high lighting ≥80 cd/m^2 measured at the target. Percentage of participants achieving 20/40 or better in photopic, high-contrast, binocular, DCNVA are reported.</description>
        <time_frame>Day 30 (Hour 1)</time_frame>
        <population>ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses at Baseline and the timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Vehicle</title>
            <description>Participants received one drop of vehicle in each eye, once daily, for up to 30 days.</description>
          </group>
          <group group_id="O2">
            <title>Pilocarpine HCl Ophthalmic Solution</title>
            <description>Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Achieving 20/40 or Better in Photopic, High-contrast, Binocular, DCNVA at Day 30, Hour 1</title>
          <description>Visual acuity for near (40 cm) target was measured in photopic conditions using an eye chart. Photopic condition was defined as high lighting ≥80 cd/m^2 measured at the target. Percentage of participants achieving 20/40 or better in photopic, high-contrast, binocular, DCNVA are reported.</description>
          <population>ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses at Baseline and the timepoint.</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="153"/>
                <count group_id="O2" value="161"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="73.9"/>
                    <measurement group_id="O2" value="92.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0114</p_value>
            <p_value_desc>P-value was adjusted for multiplicity control.</p_value_desc>
            <method>Chi-squared</method>
            <param_type>Percentage Difference</param_type>
            <param_value>18.7</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>10.6</ci_lower_limit>
            <ci_upper_limit>26.7</ci_upper_limit>
            <estimate_desc>Analysis was done using Chi-square test. 95% confidence interval was calculated based on normal approximation based on pooled variance without continuity correction.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Mesopic Near Vision Presbyopia Task-based Questionnaire (NVPTQ) Performance Score at Day 30, Hour 3</title>
        <description>NVPTQ had 12 questions on 4 reading tasks(reading a paragraph from book, excerpts from an article in newspaper, portion of a nutrition label, and a section from restaurant menu). Participants completed specific reading tasks under mesopic conditions without any near-vision correction and answered 3 questions for each task, rating their vision-related reading ability as 0=I could not read any text due to problems seeing up close,1=poor,2=fair,3=good,4=very good,5=excellent;impact of squinting on performance as 0=No,I did not squint, 1=Yes,squinting helped me read some/all text, 2=Yes,but I still could not read any of the text; and satisfaction as 0=very dissatisfied to 4=very satisfied. The score based on vision related ability and impact of squinting=(Book testlet+Newspaper testlet+Menu testlet+Nutrition Label testlet)/(testlets with non-missing responses), total possible score of 0-5. Higher scores=better outcomes;positive change from Baseline=improved performance(reading ability).</description>
        <time_frame>Baseline (Day 1) to Day 30 (Hour 3)</time_frame>
        <population>ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses. Analysis of Covariance (ANCOVA) was used for analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Vehicle</title>
            <description>Participants received one drop of vehicle in each eye, once daily, for up to 30 days.</description>
          </group>
          <group group_id="O2">
            <title>Pilocarpine HCl Ophthalmic Solution</title>
            <description>Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Mesopic Near Vision Presbyopia Task-based Questionnaire (NVPTQ) Performance Score at Day 30, Hour 3</title>
          <description>NVPTQ had 12 questions on 4 reading tasks(reading a paragraph from book, excerpts from an article in newspaper, portion of a nutrition label, and a section from restaurant menu). Participants completed specific reading tasks under mesopic conditions without any near-vision correction and answered 3 questions for each task, rating their vision-related reading ability as 0=I could not read any text due to problems seeing up close,1=poor,2=fair,3=good,4=very good,5=excellent;impact of squinting on performance as 0=No,I did not squint, 1=Yes,squinting helped me read some/all text, 2=Yes,but I still could not read any of the text; and satisfaction as 0=very dissatisfied to 4=very satisfied. The score based on vision related ability and impact of squinting=(Book testlet+Newspaper testlet+Menu testlet+Nutrition Label testlet)/(testlets with non-missing responses), total possible score of 0-5. Higher scores=better outcomes;positive change from Baseline=improved performance(reading ability).</description>
          <population>ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses. Analysis of Covariance (ANCOVA) was used for analysis.</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="148"/>
                <count group_id="O2" value="154"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6" spread="0.11"/>
                    <measurement group_id="O2" value="1.4" spread="0.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0114</p_value>
            <p_value_desc>Analysis of covariance (ANCOVA) was used with study intervention group, age group, Baseline binocular DCNVA severity, iris color (brown/non-brown), emmetrope/non-emmetrope, and Baseline domain score as fixed effects.</p_value_desc>
            <method>ANCOVA</method>
            <method_desc>P-value was adjusted for multiplicity control.</method_desc>
            <param_type>LS Mean Difference</param_type>
            <param_value>0.8</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.14</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.6</ci_lower_limit>
            <ci_upper_limit>1.1</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Photopic, High-contrast, Binocular Distance-corrected Intermediate Visual Acuity (DCIVA) Letters at Day 30, Hour 3</title>
        <description>Visual acuity for intermediate (66 cm) target was measured in photopic conditions using an eye chart. Photopic condition was defined as high lighting ≥80 cd/m^2 measured at the target. A positive change from Baseline indicates improvement in visual acuity. MMRM was used for analyses.</description>
        <time_frame>Baseline (Day 1) to Day 30 (Hour 3)</time_frame>
        <population>ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>Vehicle</title>
            <description>Participants received one drop of vehicle in each eye, once daily, for up to 30 days.</description>
          </group>
          <group group_id="O2">
            <title>Pilocarpine HCl Ophthalmic Solution</title>
            <description>Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Photopic, High-contrast, Binocular Distance-corrected Intermediate Visual Acuity (DCIVA) Letters at Day 30, Hour 3</title>
          <description>Visual acuity for intermediate (66 cm) target was measured in photopic conditions using an eye chart. Photopic condition was defined as high lighting ≥80 cd/m^2 measured at the target. A positive change from Baseline indicates improvement in visual acuity. MMRM was used for analyses.</description>
          <population>ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses.</population>
          <units>letters read correctly</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="153"/>
                <count group_id="O2" value="161"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.1" spread="0.42"/>
                    <measurement group_id="O2" value="6.6" spread="0.41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0114</p_value>
            <p_value_desc>MMRM with fixed effects: study intervention group,visit,visit by study intervention group interaction,age group,Baseline binocular DCNVA severity,iris color,emmetrope/non-emmetrope, Baseline value, and Baseline value by visit interaction was used.</p_value_desc>
            <method>MMRM</method>
            <method_desc>P-value was adjusted for multiplicity control.</method_desc>
            <param_type>LS Mean Difference</param_type>
            <param_value>3.5</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.55</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>2.4</ci_lower_limit>
            <ci_upper_limit>4.6</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Gaining 3-lines or More in Mesopic, High-contrast, Binocular, DCNVA at Day 30, Hour 10</title>
        <description>Visual acuity for near (40cm) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 cd/m^2measured at the target. Percentage of participants with 3 lines or more improvement from Baseline in mesopic, high-contrast, binocular DCNVA are reported.</description>
        <time_frame>Baseline (Day1) to Day 30 (Hour 10)</time_frame>
        <population>ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses at Baseline and the timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Vehicle</title>
            <description>Participants received one drop of vehicle in each eye, once daily, for up to 30 days.</description>
          </group>
          <group group_id="O2">
            <title>Pilocarpine HCl Ophthalmic Solution</title>
            <description>Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Gaining 3-lines or More in Mesopic, High-contrast, Binocular, DCNVA at Day 30, Hour 10</title>
          <description>Visual acuity for near (40cm) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 cd/m^2measured at the target. Percentage of participants with 3 lines or more improvement from Baseline in mesopic, high-contrast, binocular DCNVA are reported.</description>
          <population>ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses at Baseline and the timepoint.</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="152"/>
                <count group_id="O2" value="160"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.6"/>
                    <measurement group_id="O2" value="7.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>1.0000</p_value>
            <p_value_desc>P-value was adjusted for multiplicity control.</p_value_desc>
            <method>Chi-squared</method>
            <param_type>Percentage Difference</param_type>
            <param_value>-1.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-7.1</ci_lower_limit>
            <ci_upper_limit>5.0</ci_upper_limit>
            <estimate_desc>Analysis was done using Chi-square test. 95% confidence interval for the percentage differences was calculated based on the normal approximation based on pooled variance without continuity correction.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Mesopic, High-contrast, Binocular DCNVA Letters at Day 30, Hour 0.25</title>
        <description>Visual acuity for near (40 cm) target was measured in mesopic conditions. Mesopic condition was defined as low lighting 3.2 to 3.5 cd/m^2 measured at the target. A positive change from Baseline indicates improvement in visual acuity. MMRM was used for analyses.</description>
        <time_frame>Baseline (Day 1) to Day 30 (Hour 0.25)</time_frame>
        <population>ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>Vehicle</title>
            <description>Participants received one drop of vehicle in each eye, once daily, for up to 30 days.</description>
          </group>
          <group group_id="O2">
            <title>Pilocarpine HCl Ophthalmic Solution</title>
            <description>Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Mesopic, High-contrast, Binocular DCNVA Letters at Day 30, Hour 0.25</title>
          <description>Visual acuity for near (40 cm) target was measured in mesopic conditions. Mesopic condition was defined as low lighting 3.2 to 3.5 cd/m^2 measured at the target. A positive change from Baseline indicates improvement in visual acuity. MMRM was used for analyses.</description>
          <population>ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses.</population>
          <units>letters correctly read</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="153"/>
                <count group_id="O2" value="158"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.7" spread="0.50"/>
                    <measurement group_id="O2" value="6.3" spread="0.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0114</p_value>
            <p_value_desc>MMRM with fixed effects: study intervention group,visit,visit by study intervention group interaction,age group,Baseline binocular DCNVA severity,iris color,emmetrope/non-emmetrope, Baseline value, and Baseline value by visit interaction was used.</p_value_desc>
            <method>MMRM</method>
            <method_desc>P-value was adjusted for multiplicity control.</method_desc>
            <param_type>LS Mean Difference</param_type>
            <param_value>2.6</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.66</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.3</ci_lower_limit>
            <ci_upper_limit>3.9</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Achieving 20/40 or Better in Photopic, High-contrast, Binocular, DCNVA at Day 30, Hour 3</title>
        <description>Visual acuity for near (40 cm) target was measured in mesopic conditions using an eye chart. Photopic condition was defined as high lighting ≥80 cd/m^2 measured at the target. Percentage of participants achieving 20/40 or better in photopic, high-contrast, binocular, DCNVA are reported.</description>
        <time_frame>Day 30 (Hour 3)</time_frame>
        <population>ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses at Baseline and the timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Vehicle</title>
            <description>Participants received one drop of vehicle in each eye, once daily, for up to 30 days.</description>
          </group>
          <group group_id="O2">
            <title>Pilocarpine HCl Ophthalmic Solution</title>
            <description>Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Achieving 20/40 or Better in Photopic, High-contrast, Binocular, DCNVA at Day 30, Hour 3</title>
          <description>Visual acuity for near (40 cm) target was measured in mesopic conditions using an eye chart. Photopic condition was defined as high lighting ≥80 cd/m^2 measured at the target. Percentage of participants achieving 20/40 or better in photopic, high-contrast, binocular, DCNVA are reported.</description>
          <population>ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses at Baseline and the timepoint.</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="153"/>
                <count group_id="O2" value="161"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="71.9"/>
                    <measurement group_id="O2" value="84.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0171</p_value>
            <p_value_desc>P-value was adjusted for multiplicity control.</p_value_desc>
            <method>Chi-squared</method>
            <param_type>Percentage Difference</param_type>
            <param_value>12.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>3.5</ci_lower_limit>
            <ci_upper_limit>21.6</ci_upper_limit>
            <estimate_desc>Analysis was done using Chi-square test. 95% confidence interval for the percentage differences was calculated based on the normal approximation based on pooled variance without continuity correction.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Mesopic NVPTQ Satisfaction Score at Day 30, Hour 3</title>
        <description>NVPTQ had 12 questions on 4 reading tasks(reading a paragraph from book, excerpts from an article in newspaper, portion of a nutrition label, and a section from restaurant menu). Participants completed specific reading tasks under mesopic conditions without any near-vision correction and answered 3 questions for each task, rating their vision-related reading ability as 0=I could not read any text due to problems seeing up close to 5=excellent; impact of squinting on performance as 0=No, I did not squint, 1=Yes, squinting helped me read some/all text, 2=Yes, but I still could not read any of the text; and satisfaction as 0=very dissatisfied,1=dissatisfied,2=neither satisfied nor dissatisfied,3=satisfied, 4=very satisfied. The score based on satisfaction items=(Book testlet+Newspaper testlet+Menu testlet+Nutrition Label testlet)/(testlets with non-missing responses) for a total possible score of 0 to 4. Higher scores=better outcomes; a positive change from Baseline=higher satisfaction.</description>
        <time_frame>Baseline (Day 1) to Day 30 (Hour 3)</time_frame>
        <population>ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses. ANCOVA was used for analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Vehicle</title>
            <description>Participants received one drop of vehicle in each eye, once daily, for up to 30 days.</description>
          </group>
          <group group_id="O2">
            <title>Pilocarpine HCl Ophthalmic Solution</title>
            <description>Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Mesopic NVPTQ Satisfaction Score at Day 30, Hour 3</title>
          <description>NVPTQ had 12 questions on 4 reading tasks(reading a paragraph from book, excerpts from an article in newspaper, portion of a nutrition label, and a section from restaurant menu). Participants completed specific reading tasks under mesopic conditions without any near-vision correction and answered 3 questions for each task, rating their vision-related reading ability as 0=I could not read any text due to problems seeing up close to 5=excellent; impact of squinting on performance as 0=No, I did not squint, 1=Yes, squinting helped me read some/all text, 2=Yes, but I still could not read any of the text; and satisfaction as 0=very dissatisfied,1=dissatisfied,2=neither satisfied nor dissatisfied,3=satisfied, 4=very satisfied. The score based on satisfaction items=(Book testlet+Newspaper testlet+Menu testlet+Nutrition Label testlet)/(testlets with non-missing responses) for a total possible score of 0 to 4. Higher scores=better outcomes; a positive change from Baseline=higher satisfaction.</description>
          <population>ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses. ANCOVA was used for analysis.</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="148"/>
                <count group_id="O2" value="154"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6" spread="0.11"/>
                    <measurement group_id="O2" value="1.4" spread="0.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0114</p_value>
            <p_value_desc>ANCOVA was used with study intervention group, age group, baseline binocular DCNVA severity, iris color (brown/non-brown), emmetrope/non-emmetrope, and baseline domain score as fixed effects.</p_value_desc>
            <method>ANCOVA</method>
            <method_desc>P-value was adjusted for multiplicity control.</method_desc>
            <param_type>LS Mean Difference</param_type>
            <param_value>0.8</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.13</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.5</ci_lower_limit>
            <ci_upper_limit>1.1</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Presbyopia Impact and Coping Questionnaire (PICQ) Coping Score at Day 30, Hour 3</title>
        <description>PICQ=20 questions about impact experienced by participants due to their problems over past 7 days.PICQ Coping domain had 8 items: 1:Normal-sized text,2:Small-sized text,3:Information on a computer,4:Information on a cell phone,5:Increase font size,6:Use glasses to read close,12:Hold reading materials farther out/closer,13:Squint to read. Each item had response categories:0=never to 4=all the time. Items 3, 4, 5, and 6 had additional response categories with values of 9/10 to indicate the question is not applicable to participant and were assigned missing values.PICQ Coping Score:(Item 1,2 Testlet+Item 3,4 Testlet+Item 5+Item 6+Item 12+Item 13)/non-missing responses to the 6 components of coping score where Items 1,2 Testlet=(Item1+Item2)/non-missing responses to Items 1,2;Items 3,4 Testlet=(Item3+Item4)/non-missing responses to Items 3, 4. Score ranges:0=to least amount of coping to 4=greatest amount of coping. Higher scores=poorer outcome; a negative change from Baseline=improvement.</description>
        <time_frame>Baseline (Day 1) to Day 30 (Hour 3)</time_frame>
        <population>ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses. ANCOVA was used for analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Vehicle</title>
            <description>Participants received one drop of vehicle in each eye, once daily, for up to 30 days.</description>
          </group>
          <group group_id="O2">
            <title>Pilocarpine HCl Ophthalmic Solution</title>
            <description>Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Presbyopia Impact and Coping Questionnaire (PICQ) Coping Score at Day 30, Hour 3</title>
          <description>PICQ=20 questions about impact experienced by participants due to their problems over past 7 days.PICQ Coping domain had 8 items: 1:Normal-sized text,2:Small-sized text,3:Information on a computer,4:Information on a cell phone,5:Increase font size,6:Use glasses to read close,12:Hold reading materials farther out/closer,13:Squint to read. Each item had response categories:0=never to 4=all the time. Items 3, 4, 5, and 6 had additional response categories with values of 9/10 to indicate the question is not applicable to participant and were assigned missing values.PICQ Coping Score:(Item 1,2 Testlet+Item 3,4 Testlet+Item 5+Item 6+Item 12+Item 13)/non-missing responses to the 6 components of coping score where Items 1,2 Testlet=(Item1+Item2)/non-missing responses to Items 1,2;Items 3,4 Testlet=(Item3+Item4)/non-missing responses to Items 3, 4. Score ranges:0=to least amount of coping to 4=greatest amount of coping. Higher scores=poorer outcome; a negative change from Baseline=improvement.</description>
          <population>ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses. ANCOVA was used for analysis.</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="148"/>
                <count group_id="O2" value="159"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.5" spread="0.07"/>
                    <measurement group_id="O2" value="-1.0" spread="0.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0114</p_value>
            <p_value_desc>ANCOVA was used with study intervention group, age group, Baseline binocular DCNVA severity, iris color (brown/non-brown), emmetrope/non-emmetrope, and Baseline domain score as fixed effects.</p_value_desc>
            <method>ANCOVA</method>
            <method_desc>P-value was adjusted for multiplicity control.</method_desc>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.5</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.09</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.6</ci_lower_limit>
            <ci_upper_limit>-0.3</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in PICQ Impact Score at Day 30, Hour 3</title>
        <description>PICQ had 20 questions about impact experienced by participants due to their problems seeing up over past 7 days. PICQ Impact domain had 6 items: Item 9:Rely on others,15:rest eyes,16:Feel older,17:Feel self-conscious,19:Take longer to complete a task,20:Inconvenient. First 5 impacts items included response categories: 0=never to 4=all the time. Item 20 had response categories: 0=not at all to 4=extremely. Item 9 included an additional response category with a value of 9 to indicate question was not applicable to participant and the responses were assigned missing values. PICQ Impacts Score=[(Item9+Item15+Items16,17Testlet+Item19+Item20)/(nonmissing responses to 5 components of impacts score)] where Items 16,17 Testlet=(Item16+Item17)/non-missing responses to Items 16 and 17. PICQ Impact score ranges from 0 to 4; with 0=least amount of impacts to 4=greatest amount of impacts. Higher scores correspond to poorer outcomes. A negative change from Baseline=improvement.</description>
        <time_frame>Baseline (Day 1) to Day 30 (Hour 3)</time_frame>
        <population>ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses. ANCOVA was used for analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Vehicle</title>
            <description>Participants received one drop of vehicle in each eye, once daily, for up to 30 days.</description>
          </group>
          <group group_id="O2">
            <title>Pilocarpine HCl Ophthalmic Solution</title>
            <description>Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in PICQ Impact Score at Day 30, Hour 3</title>
          <description>PICQ had 20 questions about impact experienced by participants due to their problems seeing up over past 7 days. PICQ Impact domain had 6 items: Item 9:Rely on others,15:rest eyes,16:Feel older,17:Feel self-conscious,19:Take longer to complete a task,20:Inconvenient. First 5 impacts items included response categories: 0=never to 4=all the time. Item 20 had response categories: 0=not at all to 4=extremely. Item 9 included an additional response category with a value of 9 to indicate question was not applicable to participant and the responses were assigned missing values. PICQ Impacts Score=[(Item9+Item15+Items16,17Testlet+Item19+Item20)/(nonmissing responses to 5 components of impacts score)] where Items 16,17 Testlet=(Item16+Item17)/non-missing responses to Items 16 and 17. PICQ Impact score ranges from 0 to 4; with 0=least amount of impacts to 4=greatest amount of impacts. Higher scores correspond to poorer outcomes. A negative change from Baseline=improvement.</description>
          <population>ITT Population included all randomized participants. Overall number analyzed is the number of participants with data available for analyses. ANCOVA was used for analysis.</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="148"/>
                <count group_id="O2" value="159"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.4" spread="0.06"/>
                    <measurement group_id="O2" value="-0.7" spread="0.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0114</p_value>
            <p_value_desc>ANCOVA was used with study intervention group, age group, Baseline binocular DCNVA severity, iris color (brown/non-brown), emmetrope/non-emmetrope, and Baseline domain score as fixed effects.</p_value_desc>
            <method>ANCOVA</method>
            <method_desc>P-value was adjusted for multiplicity control.</method_desc>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.3</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.08</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.4</ci_lower_limit>
            <ci_upper_limit>-0.1</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>First dose of study drug intervention to within 30 days after last dose (Up to 60 days)</time_frame>
      <desc>All-cause Mortality: All enrolled participants. Serious Adverse Events and Other (non-serious) Adverse Events: Safety Population included all participants who received at least 1 administration of study intervention.</desc>
      <group_list>
        <group group_id="E1">
          <title>Vehicle</title>
          <description>Participants received one drop of vehicle in each eye, once daily, for up to 30 days.</description>
        </group>
        <group group_id="E2">
          <title>Pilocarpine HCl Ophthalmic Solution</title>
          <description>Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="160"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="163"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="163"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (22.1)</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="15" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="163"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="159"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="163"/>
              </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>A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Therapeutic Area, Head</name_or_title>
      <organization>Allergan</organization>
      <phone>714-246-4500</phone>
      <email>clinicaltrials@allergan.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/NCT03804268
org study id: 1883-301-013
nct id: NCT03804268
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
A study to evaluate the efficacy, safety, and pharmacokinetics of pilocarpine hydrochloride
      (HCl) ophthalmic solution (AGN-190584) when administered bilaterally, once daily for 30 days
      in participants with presbyopia.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular Distance-Corrected Near Visual Acuity (DCNVA) at Day 30, Hour 3
time frame: Baseline (Day 1) to Day 30 (Hour 3)
description: Visual acuity for near (40 centimeters (cm)) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 candelas per square meter (cd/m^2) measured at the target. Percentage of participants with 3 lines or more improvement from Baseline in mesopic, high-contrast DCNVA are reported.
measure: Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular Distance-Corrected Near Visual Acuity (DCNVA) at Day 30, Hour 6
time frame: Baseline (Day 1) to Day 30 (Hour 6)
description: Visual acuity for near (40 cm) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 candelas per square meter measured at the target. Percentage of participants with 3 lines or more improvement from Baseline in mesopic, high-contrast DCNVA are reported.
measure: Percentage of Participants Gaining 3-lines or More in Mesopic, High-contrast, Binocular, DCNVA at Day 30, Hour 8
time frame: Baseline (Day 1) to Day 30 (Hour 8)
description: Visual acuity for near (40 cm) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 candelas per square meter measured at the target. Percentage of participants with 3 lines or more improvement from Baseline in mesopic, high-contrast DCNVA are reported.
measure: Change From Baseline in Mesopic, High-contrast, Binocular DCNVA Letters at Day 30, Hour 0.5
time frame: Baseline (Day 1) to Day 30 (Hour 0.5)
description: Visual acuity for near (40 cm) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 cd/m^2 measured at the target. A positive change from Baseline indicates improvement in visual acuity. Mixed effect model for repeated measures (MMRM) was used for analyses.
measure: Percentage of Participants Achieving 20/40 or Better in Photopic, High-contrast, Binocular, DCNVA at Day 30, Hour 1
time frame: Day 30 (Hour 1)
description: Visual acuity for near (40 cm) target was measured in photopic conditions using an eye chart. Photopic condition was defined as high lighting ≥80 cd/m^2 measured at the target. Percentage of participants achieving 20/40 or better in photopic, high-contrast, binocular, DCNVA are reported.
measure: Mean Change From Baseline in Mesopic Near Vision Presbyopia Task-based Questionnaire (NVPTQ) Performance Score at Day 30, Hour 3
time frame: Baseline (Day 1) to Day 30 (Hour 3)
description: NVPTQ had 12 questions on 4 reading tasks(reading a paragraph from book, excerpts from an article in newspaper, portion of a nutrition label, and a section from restaurant menu). Participants completed specific reading tasks under mesopic conditions without any near-vision correction and answered 3 questions for each task, rating their vision-related reading ability as 0=I could not read any text due to problems seeing up close,1=poor,2=fair,3=good,4=very good,5=excellent;impact of squinting on performance as 0=No,I did not squint, 1=Yes,squinting helped me read some/all text, 2=Yes,but I still could not read any of the text; and satisfaction as 0=very dissatisfied to 4=very satisfied. The score based on vision related ability and impact of squinting=(Book testlet+Newspaper testlet+Menu testlet+Nutrition Label testlet)/(testlets with non-missing responses), total possible score of 0-5. Higher scores=better outcomes;positive change from Baseline=improved performance(reading ability).
measure: Change From Baseline in Photopic, High-contrast, Binocular Distance-corrected Intermediate Visual Acuity (DCIVA) Letters at Day 30, Hour 3
time frame: Baseline (Day 1) to Day 30 (Hour 3)
description: Visual acuity for intermediate (66 cm) target was measured in photopic conditions using an eye chart. Photopic condition was defined as high lighting ≥80 cd/m^2 measured at the target. A positive change from Baseline indicates improvement in visual acuity. MMRM was used for analyses.
measure: Percentage of Participants Gaining 3-lines or More in Mesopic, High-contrast, Binocular, DCNVA at Day 30, Hour 10
time frame: Baseline (Day1) to Day 30 (Hour 10)
description: Visual acuity for near (40cm) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 cd/m^2measured at the target. Percentage of participants with 3 lines or more improvement from Baseline in mesopic, high-contrast, binocular DCNVA are reported.
measure: Change From Baseline in Mesopic, High-contrast, Binocular DCNVA Letters at Day 30, Hour 0.25
time frame: Baseline (Day 1) to Day 30 (Hour 0.25)
description: Visual acuity for near (40 cm) target was measured in mesopic conditions. Mesopic condition was defined as low lighting 3.2 to 3.5 cd/m^2 measured at the target. A positive change from Baseline indicates improvement in visual acuity. MMRM was used for analyses.
measure: Percentage of Participants Achieving 20/40 or Better in Photopic, High-contrast, Binocular, DCNVA at Day 30, Hour 3
time frame: Day 30 (Hour 3)
description: Visual acuity for near (40 cm) target was measured in mesopic conditions using an eye chart. Photopic condition was defined as high lighting ≥80 cd/m^2 measured at the target. Percentage of participants achieving 20/40 or better in photopic, high-contrast, binocular, DCNVA are reported.
measure: Mean Change From Baseline in Mesopic NVPTQ Satisfaction Score at Day 30, Hour 3
time frame: Baseline (Day 1) to Day 30 (Hour 3)
description: NVPTQ had 12 questions on 4 reading tasks(reading a paragraph from book, excerpts from an article in newspaper, portion of a nutrition label, and a section from restaurant menu). Participants completed specific reading tasks under mesopic conditions without any near-vision correction and answered 3 questions for each task, rating their vision-related reading ability as 0=I could not read any text due to problems seeing up close to 5=excellent; impact of squinting on performance as 0=No, I did not squint, 1=Yes, squinting helped me read some/all text, 2=Yes, but I still could not read any of the text; and satisfaction as 0=very dissatisfied,1=dissatisfied,2=neither satisfied nor dissatisfied,3=satisfied, 4=very satisfied. The score based on satisfaction items=(Book testlet+Newspaper testlet+Menu testlet+Nutrition Label testlet)/(testlets with non-missing responses) for a total possible score of 0 to 4. Higher scores=better outcomes; a positive change from Baseline=higher satisfaction.
measure: Mean Change From Baseline in Presbyopia Impact and Coping Questionnaire (PICQ) Coping Score at Day 30, Hour 3
time frame: Baseline (Day 1) to Day 30 (Hour 3)
description: PICQ=20 questions about impact experienced by participants due to their problems over past 7 days.PICQ Coping domain had 8 items: 1:Normal-sized text,2:Small-sized text,3:Information on a computer,4:Information on a cell phone,5:Increase font size,6:Use glasses to read close,12:Hold reading materials farther out/closer,13:Squint to read. Each item had response categories:0=never to 4=all the time. Items 3, 4, 5, and 6 had additional response categories with values of 9/10 to indicate the question is not applicable to participant and were assigned missing values.PICQ Coping Score:(Item 1,2 Testlet+Item 3,4 Testlet+Item 5+Item 6+Item 12+Item 13)/non-missing responses to the 6 components of coping score where Items 1,2 Testlet=(Item1+Item2)/non-missing responses to Items 1,2;Items 3,4 Testlet=(Item3+Item4)/non-missing responses to Items 3, 4. Score ranges:0=to least amount of coping to 4=greatest amount of coping. Higher scores=poorer outcome; a negative change from Baseline=improvement.
measure: Mean Change From Baseline in PICQ Impact Score at Day 30, Hour 3
time frame: Baseline (Day 1) to Day 30 (Hour 3)
description: PICQ had 20 questions about impact experienced by participants due to their problems seeing up over past 7 days. PICQ Impact domain had 6 items: Item 9:Rely on others,15:rest eyes,16:Feel older,17:Feel self-conscious,19:Take longer to complete a task,20:Inconvenient. First 5 impacts items included response categories: 0=never to 4=all the time. Item 20 had response categories: 0=not at all to 4=extremely. Item 9 included an additional response category with a value of 9 to indicate question was not applicable to participant and the responses were assigned missing values. PICQ Impacts Score=[(Item9+Item15+Items16,17Testlet+Item19+Item20)/(nonmissing responses to 5 components of impacts score)] where Items 16,17 Testlet=(Item16+Item17)/non-missing responses to Items 16 and 17. PICQ Impact score ranges from 0 to 4; with 0=least amount of impacts to 4=greatest amount of impacts. Higher scores correspond to poorer outcomes. A negative change from Baseline=improvement.
arm group label: Vehicle
arm group type: Placebo Comparator
description: Participants received one drop of vehicle in each eye, once daily, for up to 30 days.
arm group label: Pilocarpine HCl Ophthalmic Solution
arm group type: Experimental
description: Participants received one drop of pilocarpine HCl ophthalmic solution 1.25% in each eye, once daily, for up to 30 days.
intervention type: Other
intervention name: Vehicle
description: Vehicle, one drop in each eye, once daily, for up to 30 days.
arm group label: Vehicle
intervention type: Drug
intervention name: Pilocarpine HCl Ophthalmic Solution
description: Pilocarpine HCl ophthalmic solution 1.25%, one drop in each eye, once daily, for up to 30 days.
arm group label: Pilocarpine HCl Ophthalmic Solution
other name: AGN-190584
other name: VUITY
criteria: 
gender: All
minimum age: 40 Years
maximum age: 55 Years
healthy volunteers: No
last name: Eleonora Safyan
role: Study Director
affiliation: Allergan
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country: United States
responsible party type: Sponsor
mesh term: Presbyopia
mesh term: Ophthalmic Solutions
mesh term: Pilocarpine
sharing ipd: No
provided document: 
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participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 