<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/NCT01703559</url>
  </required_header>
  <id_info>
    <org_study_id>OP-NYX-01a2</org_study_id>
    <nct_id>NCT01703559</nct_id>
  </id_info>
  <brief_title>The Safety and Efficacy of Phentolamine Mesylate Ophthalmic Solution in Subjects With Severe Night Vision Disturbances</brief_title>
  <official_title>Double-Masked Parallel Evaluation of the Safety and Efficacy of Phentolamine Mesylate Ophthalmic Solution in Subjects With Severe Night Vision Disturbances</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ocuphire Pharma, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ocuphire Pharma, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objectives of this study are:&#xD;
&#xD;
        -  To evaluate the efficacy of phentolamine mesylate 0.5% and 1.0% ophthalmic solution&#xD;
           (Nyxol) in the treatment of night vision complaints, including reduced contrast&#xD;
           sensitivity&#xD;
&#xD;
        -  To evaluate the ocular and systemic safety of phentolamine mesylate 0.5% and 1.0%&#xD;
           ophthalmic solution (Nyxol) compared to its vehicle, a sterile, isotonic, buffered&#xD;
           aqueous solution containing mannitol and sodium acetate&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Randomized, double-masked, multiple dose Phase 2 parallel evaluation of the safety and&#xD;
      efficacy of phentolamine mesylate (PM) ophthalmic solution in 60 subjects with severe night&#xD;
      vision complaints, evaluating ocular and systemic safety and efficacy following&#xD;
      administration of phentolamine mesylate (.05% or 1%) in both eyes for 15 days.&#xD;
&#xD;
      Subjects were randomized into three groups with a 1:1:1 randomization. The groups received&#xD;
      either (1) phentolamine mesylate ophthalmic solution 0.5%, (2) phentolamine mesylate&#xD;
      ophthalmic solution 1.0%, or (3) placebo, once daily (QD) for 15 days. The treatment period&#xD;
      was 15 days, plus 6 additional days over the next 14 days. After 15 days, all subjects were&#xD;
      given the opportunity to receive an additional 6 doses of 1.0% phentolamine mesylate to be&#xD;
      taken once daily as needed over the next two weeks. There was a post-dosing follow-up&#xD;
      evaluation 7 days after the last dose. Study participants completed a night vision&#xD;
      questionnaire at pre-treatment and after 15 and 29 days.&#xD;
&#xD;
      Efficacy evaluations included contrast sensitivity (mesopic, with and without glare), mesopic&#xD;
      distance high contrast visual acuity (HCVA) and mesopic distance low contrast visual acuity&#xD;
      (LCVA). Safety evaluations included photopic distance HCVA, a complete ophthalmic examination&#xD;
      and measurement of heart rate and blood pressure.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 9, 2011</start_date>
  <completion_date type="Actual">April 30, 2012</completion_date>
  <primary_completion_date type="Actual">April 16, 2012</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of Eyes With ≥ 0.3 Log Increase in Mesopic Contrast Sensitivities for at Least 2 HACSS Frequencies</measure>
    <time_frame>Days 1, 4, 8, 15, and 32</time_frame>
    <description>Proportion of eyes with an increase ≥ 0.3 log (2 or more patches) in mesopic contrast sensitivity with glare at one or more frequencies at 1.5, 3, 6, 12, and 18 cycles per degree, measured with the HACSS methodology (categorical analysis)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pupil Diameter - Change from Day 1 Pre-Dose Baseline</measure>
    <time_frame>Day 1 post-dose and Days 4, 8, and 15</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mesopic Contrast Sensitivity with Glare at 1 or More Frequencies at 1.5, 3, 6, 12, and 18 Cycles Per Degree, Measured with the HACSS Methodology - Change from Day 1 Pre-Dose Baseline</measure>
    <time_frame>Day 1 post-dose and Days 4, 8, and 15</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mesopic Contrast Sensitivity without Glare at 1 or More Frequencies at 1.5, 3, 6, 12, and 18 Cycles Per Degree, Measured with the HACSS Methodology - Change from Day 1 Pre-Dose Baseline</measure>
    <time_frame>Day 1 post-dose and Days 4, 8, and 15</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mesopic Distance High Contrast Visual Acuity (HCVA), Measured with Electronic Early Treatment Diabetic Retinopathy Study (eETDRS) Charts - Change from Day 1 Pre-Dose Baseline</measure>
    <time_frame>Day 1 post-dose and Days 4, 8, and 15</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mesopic Distance Low Contrast Visual Acuity (LCVA), Measured with eETDRS Charts - Change from Day 1 Pre-Dose Baseline</measure>
    <time_frame>Day 1 post-dose and Days 4, 8, and 15</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Subjective Evaluations of Vision (NEI Vision Function) - Change from Day 15</measure>
    <time_frame>Day 32</time_frame>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Night Vision Complaints</condition>
  <condition>Decrease in Night Vision</condition>
  <condition>Disturbance; Vision, Loss</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Administered once daily in both eyes for 15 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phentolamine Mesylate Ophthalmic Solution 0.5%</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Administered once daily in both eyes for 15 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phentolamine Mesylate Ophthalmic Solution 1.0%</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Administered once daily in both eyes for 15 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Phentolamine Mesylate Ophthalmic Solution 1.0%</intervention_name>
    <description>Phentolamine mesylate (Nyxol) ophthalmic solution 1.0% is a non-selective alpha-1 and alpha-2 adrenergic antagonist</description>
    <arm_group_label>Phentolamine Mesylate Ophthalmic Solution 1.0%</arm_group_label>
    <other_name>Nyxol®</other_name>
    <other_name>Nyxol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Phentolamine Mesylate Ophthalmic Solution 0.5%</intervention_name>
    <description>Phentolamine mesylate (Nyxol) ophthalmic solution 0.5% is a non-selective alpha-1 and alpha-2 adrenergic antagonist</description>
    <arm_group_label>Phentolamine Mesylate Ophthalmic Solution 0.5%</arm_group_label>
    <other_name>Nyxol®</other_name>
    <other_name>Nyxol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Phentolamine Mesylate Ophthalmic Solution Vehicle (Placebo)</intervention_name>
    <description>Placebo (vehicle) is a sterile, isotonic, buffered aqueous solution containing mannitol and sodium acetate</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. 18 to 45 years of age experiencing severe night vision difficulty (as reported&#xD;
             subjectively)&#xD;
&#xD;
          2. 0.3 log improvement at least 1 eye using the Holladay Automated Contrast Sensitivity&#xD;
             System (HACSS™) test at 2 of 4 spatial frequencies (3, 6, 12, and 18 cycles per&#xD;
             degree) under low and high mesopic room illumination with glare&#xD;
&#xD;
          3. Photopic visual acuity (corrected or uncorrected) of 20/25 or better&#xD;
&#xD;
          4. Able and willing to give informed consent and comply with all protocol-mandated&#xD;
             procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Cataracts (nuclear sclerosis or anterior subcapsular) of 1+ or greater&#xD;
&#xD;
          2. Contact lens wear within 4 weeks of enrollment&#xD;
&#xD;
          3. Ocular trauma within the past 6 months, or ocular surgery or laser treatment within&#xD;
             the past 3 months&#xD;
&#xD;
          4. Refractive surgery or cataract surgery in either eye&#xD;
&#xD;
          5. Use of ocular medication within 4 weeks of Visit 1&#xD;
&#xD;
          6. Clinically significant ocular disease (e.g., corneal edema, uveitis, severe&#xD;
             keratoconjunctivitis sicca, glaucoma, retinal degenerative disease) which might&#xD;
             interfere with the study&#xD;
&#xD;
          7. Any abnormality preventing reliable applanation tonometry of either eye&#xD;
&#xD;
          8. Central corneal thickness greater than 600 µ&#xD;
&#xD;
          9. Known hypersensitivity or contraindication to PM, or any component of the formulation,&#xD;
             or to topical anesthetics.&#xD;
&#xD;
         10. Contraindications to phentolamine (including history of myocardial infarction,&#xD;
             cerebrovascular spasm, cerebrovascular occlusion, coronary insufficiency, angina, or&#xD;
             other evidence suggestive of coronary artery disease)&#xD;
&#xD;
         11. Low blood pressure: systolic &lt; 100 mm Hg or diastolic &lt; 60 mm Hg&#xD;
&#xD;
         12. A history of heart rate abnormalities, such as tachycardia or arrhythmias.&#xD;
&#xD;
         13. Clinically significant systemic disease (e.g., uncontrolled diabetes, myasthenia&#xD;
             gravis, hepatic, renal, cardiovascular, or endocrine disorders) which might interfere&#xD;
             with the study&#xD;
&#xD;
         14. Use of any systemic alpha adrenergic antagonists up to 4 weeks prior to screening or&#xD;
             during the study&#xD;
&#xD;
         15. Changes of systemic medication that could have a substantial effect on ocular&#xD;
             autonomic pupil tone 4 weeks prior to screening, or anticipated during the study&#xD;
&#xD;
         16. Participation in any investigational study within the past 30 days&#xD;
&#xD;
         17. Women of childbearing potential who are pregnant, nursing, planning a pregnancy, or&#xD;
             not using a medically acceptable form of birth control. An adult woman is considered&#xD;
             to be of childbearing potential unless she is 1 year post-menopausal or 3 months&#xD;
             post-surgical sterilization. All females of childbearing potential must have a&#xD;
             negative serum pregnancy test result at the screening examination and must not intend&#xD;
             to become pregnant during the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dennis Swearingen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Celerion</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Celerion</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>67230</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>May 18, 2012</study_first_submitted>
  <study_first_submitted_qc>October 9, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 10, 2012</study_first_posted>
  <last_update_submitted>July 30, 2019</last_update_submitted>
  <last_update_submitted_qc>July 30, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 1, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Glare</keyword>
  <keyword>Starbursts</keyword>
  <keyword>Halos</keyword>
  <keyword>Reduced Contrast Sensitivity</keyword>
  <keyword>Night Vision Disturbances</keyword>
  <keyword>NVD</keyword>
  <keyword>NVDs</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Phentolamine</mesh_term>
    <mesh_term>Pharmaceutical Solutions</mesh_term>
    <mesh_term>Ophthalmic Solutions</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>June 21, 2023</submitted>
    <returned>July 14, 2023</returned>
    <submitted>July 21, 2023</submitted>
    <returned>August 11, 2023</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT01703559
org study id: OP-NYX-01a2
nct id: NCT01703559
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The objectives of this study are:

        -  To evaluate the efficacy of phentolamine mesylate 0.5% and 1.0% ophthalmic solution
           (Nyxol) in the treatment of night vision complaints, including reduced contrast
           sensitivity

        -  To evaluate the ocular and systemic safety of phentolamine mesylate 0.5% and 1.0%
           ophthalmic solution (Nyxol) compared to its vehicle, a sterile, isotonic, buffered
           aqueous solution containing mannitol and sodium acetate
Randomized, double-masked, multiple dose Phase 2 parallel evaluation of the safety and
      efficacy of phentolamine mesylate (PM) ophthalmic solution in 60 subjects with severe night
      vision complaints, evaluating ocular and systemic safety and efficacy following
      administration of phentolamine mesylate (.05% or 1%) in both eyes for 15 days.

      Subjects were randomized into three groups with a 1:1:1 randomization. The groups received
      either (1) phentolamine mesylate ophthalmic solution 0.5%, (2) phentolamine mesylate
      ophthalmic solution 1.0%, or (3) placebo, once daily (QD) for 15 days. The treatment period
      was 15 days, plus 6 additional days over the next 14 days. After 15 days, all subjects were
      given the opportunity to receive an additional 6 doses of 1.0% phentolamine mesylate to be
      taken once daily as needed over the next two weeks. There was a post-dosing follow-up
      evaluation 7 days after the last dose. Study participants completed a night vision
      questionnaire at pre-treatment and after 15 and 29 days.

      Efficacy evaluations included contrast sensitivity (mesopic, with and without glare), mesopic
      distance high contrast visual acuity (HCVA) and mesopic distance low contrast visual acuity
      (LCVA). Safety evaluations included photopic distance HCVA, a complete ophthalmic examination
      and measurement of heart rate and blood pressure.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Proportion of Eyes With ≥ 0.3 Log Increase in Mesopic Contrast Sensitivities for at Least 2 HACSS Frequencies
time frame: Days 1, 4, 8, 15, and 32
description: Proportion of eyes with an increase ≥ 0.3 log (2 or more patches) in mesopic contrast sensitivity with glare at one or more frequencies at 1.5, 3, 6, 12, and 18 cycles per degree, measured with the HACSS methodology (categorical analysis)
measure: Pupil Diameter - Change from Day 1 Pre-Dose Baseline
time frame: Day 1 post-dose and Days 4, 8, and 15
measure: Mesopic Contrast Sensitivity with Glare at 1 or More Frequencies at 1.5, 3, 6, 12, and 18 Cycles Per Degree, Measured with the HACSS Methodology - Change from Day 1 Pre-Dose Baseline
time frame: Day 1 post-dose and Days 4, 8, and 15
measure: Mesopic Contrast Sensitivity without Glare at 1 or More Frequencies at 1.5, 3, 6, 12, and 18 Cycles Per Degree, Measured with the HACSS Methodology - Change from Day 1 Pre-Dose Baseline
time frame: Day 1 post-dose and Days 4, 8, and 15
measure: Mesopic Distance High Contrast Visual Acuity (HCVA), Measured with Electronic Early Treatment Diabetic Retinopathy Study (eETDRS) Charts - Change from Day 1 Pre-Dose Baseline
time frame: Day 1 post-dose and Days 4, 8, and 15
measure: Mesopic Distance Low Contrast Visual Acuity (LCVA), Measured with eETDRS Charts - Change from Day 1 Pre-Dose Baseline
time frame: Day 1 post-dose and Days 4, 8, and 15
measure: Subjective Evaluations of Vision (NEI Vision Function) - Change from Day 15
time frame: Day 32
arm group label: Placebo
arm group type: Placebo Comparator
description: Administered once daily in both eyes for 15 days
arm group label: Phentolamine Mesylate Ophthalmic Solution 0.5%
arm group type: Experimental
description: Administered once daily in both eyes for 15 days
arm group label: Phentolamine Mesylate Ophthalmic Solution 1.0%
arm group type: Experimental
description: Administered once daily in both eyes for 15 days
intervention type: Drug
intervention name: Phentolamine Mesylate Ophthalmic Solution 1.0%
description: Phentolamine mesylate (Nyxol) ophthalmic solution 1.0% is a non-selective alpha-1 and alpha-2 adrenergic antagonist
arm group label: Phentolamine Mesylate Ophthalmic Solution 1.0%
other name: Nyxol®
other name: Nyxol
intervention type: Drug
intervention name: Phentolamine Mesylate Ophthalmic Solution 0.5%
description: Phentolamine mesylate (Nyxol) ophthalmic solution 0.5% is a non-selective alpha-1 and alpha-2 adrenergic antagonist
arm group label: Phentolamine Mesylate Ophthalmic Solution 0.5%
other name: Nyxol®
other name: Nyxol
intervention type: Other
intervention name: Phentolamine Mesylate Ophthalmic Solution Vehicle (Placebo)
description: Placebo (vehicle) is a sterile, isotonic, buffered aqueous solution containing mannitol and sodium acetate
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Dennis Swearingen, MD
role: Principal Investigator
affiliation: Celerion
facility: 
country: United States
responsible party type: Sponsor
mesh term: Phentolamine
mesh term: Pharmaceutical Solutions
mesh term: Ophthalmic Solutions
sharing ipd: No
submitted: June 21, 2023
returned: July 14, 2023
submitted: July 21, 2023
returned: August 11, 2023