<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/NCT03293992</url>
  </required_header>
  <id_info>
    <org_study_id>BP39863</org_study_id>
    <nct_id>NCT03293992</nct_id>
  </id_info>
  <brief_title>A Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7058584 Following 7 Days of Instillation of Eye Drops in Patients With Primary Open Angle Glaucoma or Ocular Hypertension</brief_title>
  <official_title>A Phase I, Multi-Center, Randomized, Adaptive, Investigator/Patient Masked, Multiple-Ascending Dose, Placebo and Active Comparator-Controlled Parallel Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7058584 Following 7 Days of Topical Instillation of Eye Drops in Patients With Primary Open Angle Glaucoma or Ocular Hypertension</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hoffmann-La Roche</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>
      This is a Phase I, multi-center, randomized, adaptive, investigator/patient-masked,&#xD;
      placebo-controlled, parallel multiple-ascending dose study (Part A) with an extension&#xD;
      including up to two selected doses from Part A and latanoprost 0.005% as active comparator&#xD;
      (Part B).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 10, 2017</start_date>
  <completion_date type="Actual">December 21, 2017</completion_date>
  <primary_completion_date type="Actual">December 15, 2017</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence, Severity, and Causal Relationship of Ocular and Systemic Adverse Events (AEs)</measure>
    <time_frame>Up to 12 weeks</time_frame>
    <description>An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of Abnormal Laboratory Findings</measure>
    <time_frame>Up to 12 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of Blood Pressure Abnormalities</measure>
    <time_frame>Up to 12 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of Pulse Rate Abnormalities</measure>
    <time_frame>Up to 12 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of Electrocardiogram (ECG) Findings</measure>
    <time_frame>Up to 12 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Mean Intraocular pressure (IOP) After 7 Days of Study Drug Administration</measure>
    <time_frame>7 days</time_frame>
    <description>IOP will be assessed by Goldman Applanation tonometry.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Mean Intraocular pressure (IOP) at Matched Clock-Times After 7 Days of Study Drug Administration</measure>
    <time_frame>7 days</time_frame>
    <description>IOP will be assessed by Goldmann Applanation tonometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax of RO7058584</measure>
    <time_frame>Up to Day 8</time_frame>
    <description>Cmax is the maximum observed plasma concentration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax of RO7058584</measure>
    <time_frame>Up to Day 8</time_frame>
    <description>Tmax is the time to maximum observed plasma concentration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ctrough of RO7058584</measure>
    <time_frame>Up to Day 8</time_frame>
    <description>Ctrough is the concentration at the end of a dosing interval before the next dose administration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-24h of RO7058584</measure>
    <time_frame>Up to Day 8</time_frame>
    <description>AUC0-24h is the area under the plasma concentration versus time curve (AUC) from Time 0 to 24 h post-dose.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">27</enrollment>
  <condition>Glaucoma, Open-angle</condition>
  <condition>Ocular Hypertension</condition>
  <arm_group>
    <arm_group_label>0.01% RO7058584 or Matching Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>0.1% RO7058584 or Matching Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>1% RO7058584 or Matching Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>RO7058584 and Latanoprost 0.005%</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>0.01% RO7058584</intervention_name>
    <description>Once daily morning administration for 7 days</description>
    <arm_group_label>0.01% RO7058584 or Matching Placebo</arm_group_label>
    <arm_group_label>RO7058584 and Latanoprost 0.005%</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>0.1% RO7058584</intervention_name>
    <description>Once daily morning administration for 7 days</description>
    <arm_group_label>0.1% RO7058584 or Matching Placebo</arm_group_label>
    <arm_group_label>RO7058584 and Latanoprost 0.005%</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>1% RO7058584</intervention_name>
    <description>Once daily morning administration for 7 days</description>
    <arm_group_label>1% RO7058584 or Matching Placebo</arm_group_label>
    <arm_group_label>RO7058584 and Latanoprost 0.005%</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Matching Placebo</intervention_name>
    <description>Once daily morning administration for 7 days</description>
    <arm_group_label>0.01% RO7058584 or Matching Placebo</arm_group_label>
    <arm_group_label>0.1% RO7058584 or Matching Placebo</arm_group_label>
    <arm_group_label>1% RO7058584 or Matching Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Latanoprost 0.005%</intervention_name>
    <description>Once daily morning or evening dosing</description>
    <arm_group_label>RO7058584 and Latanoprost 0.005%</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18 to 90 years of age inclusive, at the time of signing the informed consent form&#xD;
&#xD;
          -  Confirmed diagnosis of ocular hypertension (OHT) or primary open-angle glaucoma (POAG)&#xD;
             in both eyes as determined by the investigator at screening&#xD;
&#xD;
          -  Treatment-naïve participants or participants who are able to safely stop their&#xD;
             Intraocular pressure (IOP)-lowering medication(s) prior to randomization according to&#xD;
             the required minimum washout periods&#xD;
&#xD;
          -  At baseline visit, IOP ≥ 24 millimeters of mercury (mmHg) in the morning (8:00 AM ±&#xD;
             1h) and ≥ 22 mmHg in the afternoon (2:00 PM ± 1h) measurement in the same eye and ≤ 34&#xD;
             mmHg at all timepoints in both eyes&#xD;
&#xD;
          -  Best corrected logarithm of the minimum angle of resolution (logMAR) visual acuity&#xD;
             score of 0.7 or better in each eye as measured by Early Treatment Diabetic Retinopathy&#xD;
             Study (ETDRS) visual acuity test at screening&#xD;
&#xD;
          -  Central corneal thickness (pachymetry) measurement 450 to 620 micrometers (μm) in both&#xD;
             eyes at screening&#xD;
&#xD;
          -  Cup-to-disc ratio ≤ 0.8 (both eyes) at screening&#xD;
&#xD;
          -  Anterior chamber angle is open and non-occludable (both eyes) as confirmed by the&#xD;
             investigator by gonioscopy examination at screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Advanced visual field defects&#xD;
&#xD;
          -  Other forms of glaucoma than POAG or OHT&#xD;
&#xD;
          -  Any abnormality preventing reliable applanation tonometry&#xD;
&#xD;
          -  Any clinically significant corneal scarring, haze or opacity&#xD;
&#xD;
          -  Uncooperativeness of the participant that restricts adequate examination of IOP,&#xD;
             ocular fundus or anterior chamber&#xD;
&#xD;
          -  Any presence or history of uveitis or other history of any ocular inflammatory&#xD;
             disease.&#xD;
&#xD;
          -  History or signs of penetrating ocular trauma&#xD;
&#xD;
          -  Risk of visual field or visual acuity worsening in either eye as a consequence of&#xD;
             glaucoma progression or consequence of participation in the trial or any other ocular&#xD;
             disease, according to the investigator's best judgment&#xD;
&#xD;
          -  History of any glaucoma surgery&#xD;
&#xD;
          -  History of refractive surgery&#xD;
&#xD;
          -  Any other intra-ocular surgery within six months of screening&#xD;
&#xD;
          -  Any active ocular disease requiring treatment.&#xD;
&#xD;
          -  Use of any listed prohibited medications&#xD;
&#xD;
          -  Current enrollment or past participation within the last 30 days before the screening&#xD;
             visit in any other clinical study involving an investigational study treatment or any&#xD;
             other type of medical research&#xD;
&#xD;
          -  Any participant who is the investigator or any sub-investigator, research assistant,&#xD;
             pharmacist, study coordinator, other staff thereof, directly involved in the conduct&#xD;
             of the protocol&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Arizona Eye Center</name>
      <address>
        <city>Chandler</city>
        <state>Arizona</state>
        <zip>85225</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <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>
    <facility>
      <name>United Med Res Inst</name>
      <address>
        <city>Inglewood</city>
        <state>California</state>
        <zip>90301</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>Rocky Mountain Lions Eye Inst</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eye Care Centers Management, Inc. (Clayton Eye Center)</name>
      <address>
        <city>Morrow</city>
        <state>Georgia</state>
        <zip>30260</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Coastal Research Associates</name>
      <address>
        <city>Roswell</city>
        <state>Georgia</state>
        <zip>30076</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texan Eye/Keystone Research</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78731</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>September 21, 2017</study_first_submitted>
  <study_first_submitted_qc>September 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 26, 2017</study_first_posted>
  <last_update_submitted>March 27, 2020</last_update_submitted>
  <last_update_submitted_qc>March 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 31, 2020</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>Glaucoma</mesh_term>
    <mesh_term>Glaucoma, Open-Angle</mesh_term>
    <mesh_term>Ocular Hypertension</mesh_term>
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Latanoprost</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/NCT03293992
org study id: BP39863
nct id: NCT03293992
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase I, multi-center, randomized, adaptive, investigator/patient-masked,
      placebo-controlled, parallel multiple-ascending dose study (Part A) with an extension
      including up to two selected doses from Part A and latanoprost 0.005% as active comparator
      (Part B).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Incidence, Severity, and Causal Relationship of Ocular and Systemic Adverse Events (AEs)
time frame: Up to 12 weeks
description: An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
measure: Incidence of Abnormal Laboratory Findings
time frame: Up to 12 weeks
measure: Incidence of Blood Pressure Abnormalities
time frame: Up to 12 weeks
measure: Incidence of Pulse Rate Abnormalities
time frame: Up to 12 weeks
measure: Incidence of Electrocardiogram (ECG) Findings
time frame: Up to 12 weeks
measure: Change From Baseline in Mean Intraocular pressure (IOP) After 7 Days of Study Drug Administration
time frame: 7 days
description: IOP will be assessed by Goldman Applanation tonometry.
measure: Change From Baseline in Mean Intraocular pressure (IOP) at Matched Clock-Times After 7 Days of Study Drug Administration
time frame: 7 days
description: IOP will be assessed by Goldmann Applanation tonometry
measure: Cmax of RO7058584
time frame: Up to Day 8
description: Cmax is the maximum observed plasma concentration.
measure: Tmax of RO7058584
time frame: Up to Day 8
description: Tmax is the time to maximum observed plasma concentration.
measure: Ctrough of RO7058584
time frame: Up to Day 8
description: Ctrough is the concentration at the end of a dosing interval before the next dose administration.
measure: AUC0-24h of RO7058584
time frame: Up to Day 8
description: AUC0-24h is the area under the plasma concentration versus time curve (AUC) from Time 0 to 24 h post-dose.
arm group label: 0.01% RO7058584 or Matching Placebo
arm group type: Experimental
arm group label: 0.1% RO7058584 or Matching Placebo
arm group type: Experimental
arm group label: 1% RO7058584 or Matching Placebo
arm group type: Experimental
arm group label: RO7058584 and Latanoprost 0.005%
arm group type: Experimental
intervention type: Drug
intervention name: 0.01% RO7058584
description: Once daily morning administration for 7 days
arm group label: 0.01% RO7058584 or Matching Placebo
arm group label: RO7058584 and Latanoprost 0.005%
intervention type: Drug
intervention name: 0.1% RO7058584
description: Once daily morning administration for 7 days
arm group label: 0.1% RO7058584 or Matching Placebo
arm group label: RO7058584 and Latanoprost 0.005%
intervention type: Drug
intervention name: 1% RO7058584
description: Once daily morning administration for 7 days
arm group label: 1% RO7058584 or Matching Placebo
arm group label: RO7058584 and Latanoprost 0.005%
intervention type: Drug
intervention name: Matching Placebo
description: Once daily morning administration for 7 days
arm group label: 0.01% RO7058584 or Matching Placebo
arm group label: 0.1% RO7058584 or Matching Placebo
arm group label: 1% RO7058584 or Matching Placebo
intervention type: Drug
intervention name: Latanoprost 0.005%
description: Once daily morning or evening dosing
arm group label: RO7058584 and Latanoprost 0.005%
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Glaucoma
mesh term: Glaucoma, Open-Angle
mesh term: Ocular Hypertension
mesh term: Hypertension
mesh term: Latanoprost