<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/NCT02242032</url>
  </required_header>
  <id_info>
    <org_study_id>P-321-101</org_study_id>
    <nct_id>NCT02242032</nct_id>
  </id_info>
  <brief_title>Study of the Safety and Tolerability of P 321 Ophthalmic Solution in Subjects With Dry Eye Disease</brief_title>
  <official_title>A Double-Masked, Randomized, Placebo-Controlled Dose Escalation Study of the Safety and Tolerability of P 321 Ophthalmic Solution in Subjects With Dry Eye Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Parion Sciences</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Parion Sciences</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to assess the safety and tolerability of P-321 Ophthalmic&#xD;
      Solution in subjects with mild to moderate dry eye disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single-center, dose escalation, randomized, double-masked, placebo-controlled,&#xD;
      Phase 1/2a trial designed to evaluate the safety and tolerability of P-321 Ophthalmic&#xD;
      Solution in subjects with mild to moderate dry eye for up to 4-weeks of treatment and up to 8&#xD;
      scheduled in clinic visits. This study will conduct a consecutive dose escalation of the&#xD;
      following concentrations of P-321 Ophthalmic Solution given two times a day via ocular&#xD;
      instillation: 0.0005% (Cohort 1), 0.0015% (Cohort 2), 0.005% (Cohort 3), and 0.01% (Cohort&#xD;
      4). Up to 48 subjects will be enrolled in four consecutive cohorts. Subjects will be&#xD;
      randomized to P-321 Ophthalmic Solution or placebo in a 3:1 ratio.&#xD;
&#xD;
      Safety and tolerability assessments, drug plasma concentrations and drug urine concentrations&#xD;
      will be evaluated throughout the study in all cohorts.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">March 2015</completion_date>
  <primary_completion_date type="Actual">March 2015</primary_completion_date>
  <phase>Phase 1</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>Number of subjects with adverse events</measure>
    <time_frame>Days 0, 1, 2, 8, 15, 22 and 28</time_frame>
    <description>One primary objective of this trial is to assess the safety of P-321 Ophthalmic Solution versus placebo in subjects with moderate dry eye disease at 14 days (Cohorts 1-4) and 28 days (Cohort 4 only).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes from baseline in 14 days in visual acuity.</measure>
    <time_frame>Change from baseline at 14 days.</time_frame>
    <description>Change from baseline at 14 days in visual acuity.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline at 28 days in visual acuity for Cohort 4 only.</measure>
    <time_frame>Change from baseline at 28 days in visual acuity.</time_frame>
    <description>Change from baseline at 28 days in visual acuity for Cohort 4 only.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes from baseline at 14 days in corneal staining.</measure>
    <time_frame>Changes from baseline at 14 days.</time_frame>
    <description>Changes from baseline at 14 days in corneal staining.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes from baseline at 28 days in corneal staining for cohort 4 only.</measure>
    <time_frame>Changes from baseline at 28 days.</time_frame>
    <description>Changes from baseline at 28 days in corneal staining for cohort 4 only.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes from baseline at 14 days in conjunctival staining.</measure>
    <time_frame>Changes from baseline at 14 days</time_frame>
    <description>Changes from baseline at 14 days in conjunctival staining.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes from baseline at 28 days in conjunctival staining for Cohort 4 only.</measure>
    <time_frame>Changes from baseline at 28 days</time_frame>
    <description>Changes from baseline at 28 days in conjunctival staining for Cohort 4 only.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes from baseline at 14 days in intraocular pressure.</measure>
    <time_frame>Changes from baseline at 14 days.</time_frame>
    <description>Changes from baseline at 14 days in intraocular pressure.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes from baseline at 28 days in intraocular pressure. for Cohort 4 only.</measure>
    <time_frame>Changes from baseline at 28 days</time_frame>
    <description>Changes from baseline at 28 days in intraocular pressure. for Cohort 4 only.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes from baseline at 14 days in ophthalmoscopy.</measure>
    <time_frame>Changes from baseline at 14 days</time_frame>
    <description>Changes from baseline at 14 days in ophthalmoscopy.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes from baseline at 28 days in ophthalmoscopy for Cohort 4 only.</measure>
    <time_frame>Changes from baseline at 28 days</time_frame>
    <description>Changes from baseline at 28 days in ophthalmoscopy for Cohort 4 only.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Measure plasma P-321 concentrations</measure>
    <time_frame>Pre-dose 0.5, 1, 2, 4, and 6 hours post dosing on Days 1 and Day 15 and pre-dose on Day 8.</time_frame>
    <description>Drug plasma concentrations will be evaluated pre-dose 0.5, 1, 2, 4, and 6 hours post dosing on Days 1 and 15 and pre-dose on Day 8.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measure urine concentrations of P-321</measure>
    <time_frame>At multiple timepoints throughout the study</time_frame>
    <description>Drug urine concentrations will be evaluated at Day 1 and Day 15.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measure tear concentrations of P-321</measure>
    <time_frame>pre-dose 0.5, 1, 2, 4, and 6 hours post dosing on Day 1 and Day 15 and pre-dose on Day 8.</time_frame>
    <description>Drug tear concentrations will be evaluated at all visits post dose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measure plasma P-321 concentrations in Cohort 4</measure>
    <time_frame>pre-dose on Day 8 and Day 22, and pre-dose, 0.5, 1, 2, 4, 6, 8, and 24 hours post-dose on Day 28</time_frame>
    <description>Measure plasma P-321 concentrations in Cohort 4</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measure urine concentrations of P-321 in Cohort 4</measure>
    <time_frame>Day 28</time_frame>
    <description>Measure urine concentrations of P-321 in Cohort 4</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measure tear concentrations of P-321 in Cohort 4</measure>
    <time_frame>pre-dose on Day 8 and Day 22, and pre-dose, 0.5, 1, 2, 4, 6, 8, and 24 hours post-dose on Day 28</time_frame>
    <description>Measure tear concentrations of P-321 in Cohort 4</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">53</enrollment>
  <condition>Dry Eye Disease</condition>
  <arm_group>
    <arm_group_label>P-321</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>P-321 Ophthalmic Solution</description>
  </arm_group>
  <arm_group>
    <arm_group_label>P-321 Ophthalmic Solution Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>P-321 Ophthalmic Solution Placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>P-321 Ophthalmic Solution</intervention_name>
    <arm_group_label>P-321</arm_group_label>
    <other_name>P-321</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>P-321 Ophthalmic Solution placebo</intervention_name>
    <description>Placebo to match P-321 Ophthalmic Solution</description>
    <arm_group_label>P-321 Ophthalmic Solution Placebo</arm_group_label>
    <other_name>placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Individuals of both genders and any race will be eligible for study participation if&#xD;
             they:&#xD;
&#xD;
               1. Provide written informed consent.&#xD;
&#xD;
               2. Are 18 - 80 years of age.&#xD;
&#xD;
               3. Corneal fluorescein staining score ≥2/15 on the NEI/Industry scale&#xD;
&#xD;
               4. Conjunctival lissamine staining score of ≥ 2/18 on the NEI/Industry scale&#xD;
&#xD;
               5. Schirmer &lt;10mm/5min&#xD;
&#xD;
               6. Are willing and able to follow instructions and can be present for the required&#xD;
                  study visits for the duration of the study.&#xD;
&#xD;
               7. Female patients of child bearing potential must have a negative urine pregnancy&#xD;
                  test at Screening and agree to use a medically acceptable form of birth control.&#xD;
                  Male subjects who are sexually active must be willing to use highly effective&#xD;
                  contraception (i.e., less than 1% failure rate) during heterosexual intercourse&#xD;
                  from Day 1 through completion of the study.&#xD;
&#xD;
               8. Have a history of Dry Eye Disease in both eyes supported by a previous clinical&#xD;
                  diagnosis or have a self-reported history of subjective complaints for at least 4&#xD;
                  months prior to Screening, low tear volume, and ocular staining.&#xD;
&#xD;
               9. Have documented history of topical lubricants at least daily or the desire to use&#xD;
                  topical lubricants in the past 4 months.&#xD;
&#xD;
              10. Have normal lid anatomy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Individuals are not eligible for study participation if:&#xD;
&#xD;
               1. Have anterior segment eye disease except primary dry eye.&#xD;
&#xD;
               2. Patients with an identifiable or suspected secondary dry eye, i.e., a documented&#xD;
                  or likely systemic, ocular, pharmacologic, post-traumatic, post-surgical, or&#xD;
                  external cause for dry eye symptoms or ocular surface staining.&#xD;
&#xD;
               3. Patients with current punctal plugs, punctal occlusion, or history of&#xD;
                  nasolacrimal duct obstruction are excluded.&#xD;
&#xD;
               4. Have a history of glaucoma or intraocular pressure (IOP) &gt; 25 mmHg at the&#xD;
                  Screening Visit (Visit 1) or a history of elevated IOP within the past year prior&#xD;
                  to Visit 1&#xD;
&#xD;
               5. Contact lenses wear in the previous 30 days or during the Treatment Phase of the&#xD;
                  study.&#xD;
&#xD;
               6. Use of lid scrubs (including baby shampoos)&#xD;
&#xD;
               7. Known hypersensitivity to the study investigational medicinal product, or&#xD;
                  formulation excipients, including amiloride or related drugs or allergies to the&#xD;
                  components of the study drug.&#xD;
&#xD;
               8. Any significant chronic illness that, in the opinion of the Principal&#xD;
                  Investigator (PI), could interfere with the study parameters.&#xD;
&#xD;
               9. Use of any investigational product or device within 30 days prior to the&#xD;
                  Screening Visit or during the study.&#xD;
&#xD;
              10. Those unable in the opinion of the PI to comply fully with the study requirements&#xD;
                  or complete the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kenneth Sall, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sall Research Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sall Research Medical Center</name>
      <address>
        <city>Artesia</city>
        <state>California</state>
        <zip>90701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2015</verification_date>
  <study_first_submitted>August 28, 2014</study_first_submitted>
  <study_first_submitted_qc>September 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 16, 2014</study_first_posted>
  <last_update_submitted>May 1, 2015</last_update_submitted>
  <last_update_submitted_qc>May 1, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 4, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>dry eye disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dry Eye Syndromes</mesh_term>
    <mesh_term>Keratoconjunctivitis Sicca</mesh_term>
    <mesh_term>Eye Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pharmaceutical Solutions</mesh_term>
    <mesh_term>Ophthalmic Solutions</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02242032
org study id: P-321-101
nct id: NCT02242032
lead sponsor: 
has dmc: No
The purpose of this study is to assess the safety and tolerability of P-321 Ophthalmic
      Solution in subjects with mild to moderate dry eye disease.
This is a single-center, dose escalation, randomized, double-masked, placebo-controlled,
      Phase 1/2a trial designed to evaluate the safety and tolerability of P-321 Ophthalmic
      Solution in subjects with mild to moderate dry eye for up to 4-weeks of treatment and up to 8
      scheduled in clinic visits. This study will conduct a consecutive dose escalation of the
      following concentrations of P-321 Ophthalmic Solution given two times a day via ocular
      instillation: 0.0005% (Cohort 1), 0.0015% (Cohort 2), 0.005% (Cohort 3), and 0.01% (Cohort
      4). Up to 48 subjects will be enrolled in four consecutive cohorts. Subjects will be
      randomized to P-321 Ophthalmic Solution or placebo in a 3:1 ratio.

      Safety and tolerability assessments, drug plasma concentrations and drug urine concentrations
      will be evaluated throughout the study in all cohorts.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of subjects with adverse events
time frame: Days 0, 1, 2, 8, 15, 22 and 28
description: One primary objective of this trial is to assess the safety of P-321 Ophthalmic Solution versus placebo in subjects with moderate dry eye disease at 14 days (Cohorts 1-4) and 28 days (Cohort 4 only).
measure: Changes from baseline in 14 days in visual acuity.
time frame: Change from baseline at 14 days.
description: Change from baseline at 14 days in visual acuity.
measure: Change from baseline at 28 days in visual acuity for Cohort 4 only.
time frame: Change from baseline at 28 days in visual acuity.
description: Change from baseline at 28 days in visual acuity for Cohort 4 only.
measure: Changes from baseline at 14 days in corneal staining.
time frame: Changes from baseline at 14 days.
description: Changes from baseline at 14 days in corneal staining.
measure: Changes from baseline at 28 days in corneal staining for cohort 4 only.
time frame: Changes from baseline at 28 days.
description: Changes from baseline at 28 days in corneal staining for cohort 4 only.
measure: Changes from baseline at 14 days in conjunctival staining.
time frame: Changes from baseline at 14 days
description: Changes from baseline at 14 days in conjunctival staining.
measure: Changes from baseline at 28 days in conjunctival staining for Cohort 4 only.
time frame: Changes from baseline at 28 days
description: Changes from baseline at 28 days in conjunctival staining for Cohort 4 only.
measure: Changes from baseline at 14 days in intraocular pressure.
time frame: Changes from baseline at 14 days.
description: Changes from baseline at 14 days in intraocular pressure.
measure: Changes from baseline at 28 days in intraocular pressure. for Cohort 4 only.
time frame: Changes from baseline at 28 days
description: Changes from baseline at 28 days in intraocular pressure. for Cohort 4 only.
measure: Changes from baseline at 14 days in ophthalmoscopy.
time frame: Changes from baseline at 14 days
description: Changes from baseline at 14 days in ophthalmoscopy.
measure: Changes from baseline at 28 days in ophthalmoscopy for Cohort 4 only.
time frame: Changes from baseline at 28 days
description: Changes from baseline at 28 days in ophthalmoscopy for Cohort 4 only.
measure: Measure plasma P-321 concentrations
time frame: Pre-dose 0.5, 1, 2, 4, and 6 hours post dosing on Days 1 and Day 15 and pre-dose on Day 8.
description: Drug plasma concentrations will be evaluated pre-dose 0.5, 1, 2, 4, and 6 hours post dosing on Days 1 and 15 and pre-dose on Day 8.
measure: Measure urine concentrations of P-321
time frame: At multiple timepoints throughout the study
description: Drug urine concentrations will be evaluated at Day 1 and Day 15.
measure: Measure tear concentrations of P-321
time frame: pre-dose 0.5, 1, 2, 4, and 6 hours post dosing on Day 1 and Day 15 and pre-dose on Day 8.
description: Drug tear concentrations will be evaluated at all visits post dose.
measure: Measure plasma P-321 concentrations in Cohort 4
time frame: pre-dose on Day 8 and Day 22, and pre-dose, 0.5, 1, 2, 4, 6, 8, and 24 hours post-dose on Day 28
description: Measure plasma P-321 concentrations in Cohort 4
measure: Measure urine concentrations of P-321 in Cohort 4
time frame: Day 28
description: Measure urine concentrations of P-321 in Cohort 4
measure: Measure tear concentrations of P-321 in Cohort 4
time frame: pre-dose on Day 8 and Day 22, and pre-dose, 0.5, 1, 2, 4, 6, 8, and 24 hours post-dose on Day 28
description: Measure tear concentrations of P-321 in Cohort 4
arm group label: P-321
arm group type: Experimental
description: P-321 Ophthalmic Solution
arm group label: P-321 Ophthalmic Solution Placebo
arm group type: Placebo Comparator
description: P-321 Ophthalmic Solution Placebo
intervention type: Drug
intervention name: P-321 Ophthalmic Solution
arm group label: P-321
other name: P-321
intervention type: Drug
intervention name: P-321 Ophthalmic Solution placebo
description: Placebo to match P-321 Ophthalmic Solution
arm group label: P-321 Ophthalmic Solution Placebo
other name: placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Kenneth Sall, MD
role: Principal Investigator
affiliation: Sall Research Medical Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Dry Eye Syndromes
mesh term: Keratoconjunctivitis Sicca
mesh term: Eye Diseases
mesh term: Pharmaceutical Solutions
mesh term: Ophthalmic Solutions