<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/NCT03794583</url>
  </required_header>
  <id_info>
    <org_study_id>RIN-PH-305</org_study_id>
    <nct_id>NCT03794583</nct_id>
  </id_info>
  <brief_title>Inhaled Treprostinil in Participants With Pulmonary Hypertension Due to Chronic Obstructive Pulmonary Disease (PH-COPD)</brief_title>
  <acronym>PERFECT OLE</acronym>
  <official_title>An Open-Label Extension Study of Inhaled Treprostinil in Patients With Pulmonary Hypertension Due to Chronic Obstructive Pulmonary Disease (PH-COPD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>United Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Lung Biotechnology PBC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>United Therapeutics</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>
      This open-label study will evaluate the safety of continued therapy with inhaled treprostinil&#xD;
      in participants who have completed Study RIN-PH-304 (NCT03496623). This study hypothesizes&#xD;
      that long-term safety findings will be similar to those observed in the randomized,&#xD;
      placebo-controlled, double-blind, adaptive study 'A Phase 3, Randomized, Placebo-controlled,&#xD;
      Double-blind, Adaptive Study to Evaluate the Safety and Efficacy of Inhaled Treprostinil in&#xD;
      Patients with Pulmonary Hypertension due to Chronic Obstructive Pulmonary Disease&#xD;
      (PH-COPD)(RIN-PH-304).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a multi-center, open-label study for eligible participants who completed all&#xD;
      scheduled study visits during the Treatment Period of Study RIN-PH-304.&#xD;
&#xD;
      Participants who provide informed consent for this open-label extension study on or prior to&#xD;
      the final study visit of RIN-PH-304 may participate in the study, provided all other&#xD;
      eligibility criteria are met. The RIN-PH-304 final study visit and the RIN-PH-305 Enrollment&#xD;
      Visit will occur on the same day.&#xD;
&#xD;
      All participants will reinitiate inhaled treprostinil at 3 breathes (18 micrograms [mcg]) 4&#xD;
      times daily (QID) during waking hours. Study drug doses should be maximized to tolerability&#xD;
      throughout the study, and dose titrations should occur as rapidly as possible (as directed by&#xD;
      the Investigator) with a target dosing regimen of 15 breaths QID or the maximum tolerated&#xD;
      dose.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Sponsor's decision&#xD;
  </why_stopped>
  <start_date type="Actual">December 21, 2018</start_date>
  <completion_date type="Actual">November 29, 2022</completion_date>
  <primary_completion_date type="Actual">November 29, 2022</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>This trial is not blinded. All participants will begin titration of study drug once all entry criteria have been met.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Treatment-Emergent Adverse Events (TEAEs)</measure>
    <time_frame>From enrollment to end of study, estimated up to 2 years.</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>6 Minute Walk Distance (6MWD)</measure>
    <time_frame>Assessed at enrollment, Week 6, and then every 12 weeks through study completion, estimated up to 2 years.</time_frame>
    <description>Participants will be instructed to walk down a corridor at a comfortable speed as far as they can manage for six minutes. Distance &lt;500 meters suggests considerable exercise limitation; Distance 500-800 meters suggests moderate limitation; Distance &gt;800 meters (with no rests) suggests mild or no limitation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Borg Dyspnea Score</measure>
    <time_frame>Assessed at enrollment, Week 6, and then every 12 weeks through study completion, estimated up to 2 years.</time_frame>
    <description>The modified 0-10 category-ratio Borg scale is one in which the participants rate the maximum level of dyspnea they experienced during the Six Minute Walk Test (6MWT). Scores range from 0 (for the best condition) and 10 (for the worst condition).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>N-terminal Pro-brain Natriuretic Peptide (NT-pro-BNP)</measure>
    <time_frame>Assessed at enrollment, Week 6, and then every 12 weeks through study completion, estimated up to 2 years.</time_frame>
    <description>The NT-proBNP concentration is a biomarker associated with changes in right heart morphology and function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Saturation Peripheral Capillary Oxygenation (SpO2)</measure>
    <time_frame>Assessed at enrollment, Week 6, and then every 12 weeks through study completion, estimated up to 2 years.</time_frame>
    <description>SpO2 will be assessed via pulse oximetry.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart Rate</measure>
    <time_frame>Assessed at enrollment, Week 6, and then every 12 weeks through study completion, estimated up to 2 years.</time_frame>
    <description>Heart rate will be assessed via pulse oximetry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Baseline in Patient Global Assessment (PGA)</measure>
    <time_frame>Week 6, Year 1 or Discontinuation Visit (whichever occurs first)</time_frame>
    <description>The PGA is used to rate participant fatigue and shortness of breath. Participants will use the Sponsor-provided smart device for at-home capture of PGA data.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Actigraphy</measure>
    <time_frame>Baseline, Week 6, Year 1 or Discontinuation Visit (whichever occurs first)</time_frame>
    <description>Daily physical activity, including overall, non-sedentary, and moderate to vigorous physical activity will be measured via a wrist-worn medical grade physical activity monitor (actigraph).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">41</enrollment>
  <condition>Pulmonary Hypertension</condition>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <arm_group>
    <arm_group_label>Inhaled Treprostinil Solution</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Inhaled treprostinil solution (0.6 milligrams per milliliter [mg/mL], 6 mcg/breath) QID during waking hours.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Inhaled treprostinil solution</intervention_name>
    <description>Inhaled treprostinil solution per dose and schedule specified in the arm</description>
    <arm_group_label>Inhaled Treprostinil Solution</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Participant voluntarily gives informed consent to participate in the study.&#xD;
&#xD;
          2. Participant completed Study RIN-PH-304.&#xD;
&#xD;
          3. Women of childbearing potential (defined as less than 1 year post-menopausal and not&#xD;
             surgically sterile) must agree to practice abstinence or use 2 highly effective&#xD;
             methods of contraception (defined as a method of birth control that results in a low&#xD;
             failure rate, [less than 1% per year], such as approved hormonal contraceptives,&#xD;
             barrier methods [such as condom or diaphragm] used with a spermicide, or an&#xD;
             intrauterine device) for the duration of study treatment and for 48 hours after&#xD;
             discontinuing study drug.&#xD;
&#xD;
          4. Males with a partner of childbearing potential must agree to use a barrier method&#xD;
             (condom) with a spermicide for the duration of treatment and for at least 48 hours&#xD;
             after discontinuing study drug.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. The participant is pregnant or lactating.&#xD;
&#xD;
          2. The participant was prematurely discontinued from Study RIN-PH-304.&#xD;
&#xD;
          3. The participant is intolerant to inhaled prostanoid therapy.&#xD;
&#xD;
          4. The participant is unwilling or unable to use Sponsor-provided devices (actigraph,&#xD;
             spirometer, or smart device).&#xD;
&#xD;
          5. The participant is scheduled to receive another investigational drug, device, or&#xD;
             therapy during the course of this study.&#xD;
&#xD;
          6. Any other clinically significant illness or abnormal laboratory value(s) that, in the&#xD;
             opinion of the Investigator, might adversely affect the interpretation of the study&#xD;
             data.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>The University of Alabama at Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California Davis Medical Center</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Francis Sleep Allergy &amp; Lung Institute</name>
      <address>
        <city>Clearwater</city>
        <state>Florida</state>
        <zip>33765</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Vincent's Lung, Sleep, and Criticial Care Specialists</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic - Jacksonville</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miami Hospital</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pulmonary &amp; Critical Care of Atlanta</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30342</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Georgia Clinical Research</name>
      <address>
        <city>Austell</city>
        <state>Georgia</state>
        <zip>30106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Illinois Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Vincent Medical Group, Inc.</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46260</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kentuckiana Pulmonary Associates</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Maryland Medical Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spectrum Health</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49546</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Albany Medical Center</name>
      <address>
        <city>Albany</city>
        <state>New York</state>
        <zip>12208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Sinai Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Rochester Medical Center</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14623</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of North Carolina at Chapel Hill</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Carl and Edyth Lindner Research Center at The Christ Hospital</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Allegheny General Hospital</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh Medical Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inova Fairfax Hospital</name>
      <address>
        <city>Falls Church</city>
        <state>Virginia</state>
        <zip>22042</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pulmonary Associates of Richmond, Inc.</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23230</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carilion Clinic</name>
      <address>
        <city>Roanoke</city>
        <state>Virginia</state>
        <zip>24014</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Wisconsin School of Medicine and Public Health</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53792</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lady Davis Carmel Medical Centre</name>
      <address>
        <city>Haifa</city>
        <zip>34362</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hadassah-Hebrew University Hospital</name>
      <address>
        <city>Jerusalem</city>
        <zip>9112001</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rabin Medical Center</name>
      <address>
        <city>Petah Tiva</city>
        <zip>49100</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Israel</country>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>January 2, 2019</study_first_submitted>
  <study_first_submitted_qc>January 3, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 7, 2019</study_first_posted>
  <last_update_submitted>March 22, 2023</last_update_submitted>
  <last_update_submitted_qc>March 22, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Treprostinil</keyword>
  <keyword>Lung Diseases</keyword>
  <keyword>Hypertension</keyword>
  <keyword>Vascular Diseases</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
    <mesh_term>Hypertension, Pulmonary</mesh_term>
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Treprostinil</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03794583
org study id: RIN-PH-305
nct id: NCT03794583
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This open-label study will evaluate the safety of continued therapy with inhaled treprostinil
      in participants who have completed Study RIN-PH-304 (NCT03496623). This study hypothesizes
      that long-term safety findings will be similar to those observed in the randomized,
      placebo-controlled, double-blind, adaptive study 'A Phase 3, Randomized, Placebo-controlled,
      Double-blind, Adaptive Study to Evaluate the Safety and Efficacy of Inhaled Treprostinil in
      Patients with Pulmonary Hypertension due to Chronic Obstructive Pulmonary Disease
      (PH-COPD)(RIN-PH-304).
This is a multi-center, open-label study for eligible participants who completed all
      scheduled study visits during the Treatment Period of Study RIN-PH-304.

      Participants who provide informed consent for this open-label extension study on or prior to
      the final study visit of RIN-PH-304 may participate in the study, provided all other
      eligibility criteria are met. The RIN-PH-304 final study visit and the RIN-PH-305 Enrollment
      Visit will occur on the same day.

      All participants will reinitiate inhaled treprostinil at 3 breathes (18 micrograms [mcg]) 4
      times daily (QID) during waking hours. Study drug doses should be maximized to tolerability
      throughout the study, and dose titrations should occur as rapidly as possible (as directed by
      the Investigator) with a target dosing regimen of 15 breaths QID or the maximum tolerated
      dose.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: This trial is not blinded. All participants will begin titration of study drug once all entry criteria have been met.
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
time frame: From enrollment to end of study, estimated up to 2 years.
measure: 6 Minute Walk Distance (6MWD)
time frame: Assessed at enrollment, Week 6, and then every 12 weeks through study completion, estimated up to 2 years.
description: Participants will be instructed to walk down a corridor at a comfortable speed as far as they can manage for six minutes. Distance <500 meters suggests considerable exercise limitation; Distance 500-800 meters suggests moderate limitation; Distance >800 meters (with no rests) suggests mild or no limitation.
measure: Borg Dyspnea Score
time frame: Assessed at enrollment, Week 6, and then every 12 weeks through study completion, estimated up to 2 years.
description: The modified 0-10 category-ratio Borg scale is one in which the participants rate the maximum level of dyspnea they experienced during the Six Minute Walk Test (6MWT). Scores range from 0 (for the best condition) and 10 (for the worst condition).
measure: N-terminal Pro-brain Natriuretic Peptide (NT-pro-BNP)
time frame: Assessed at enrollment, Week 6, and then every 12 weeks through study completion, estimated up to 2 years.
description: The NT-proBNP concentration is a biomarker associated with changes in right heart morphology and function.
measure: Saturation Peripheral Capillary Oxygenation (SpO2)
time frame: Assessed at enrollment, Week 6, and then every 12 weeks through study completion, estimated up to 2 years.
description: SpO2 will be assessed via pulse oximetry.
measure: Heart Rate
time frame: Assessed at enrollment, Week 6, and then every 12 weeks through study completion, estimated up to 2 years.
description: Heart rate will be assessed via pulse oximetry
measure: Change in Baseline in Patient Global Assessment (PGA)
time frame: Week 6, Year 1 or Discontinuation Visit (whichever occurs first)
description: The PGA is used to rate participant fatigue and shortness of breath. Participants will use the Sponsor-provided smart device for at-home capture of PGA data.
measure: Change from Baseline in Actigraphy
time frame: Baseline, Week 6, Year 1 or Discontinuation Visit (whichever occurs first)
description: Daily physical activity, including overall, non-sedentary, and moderate to vigorous physical activity will be measured via a wrist-worn medical grade physical activity monitor (actigraph).
arm group label: Inhaled Treprostinil Solution
arm group type: Experimental
description: Inhaled treprostinil solution (0.6 milligrams per milliliter [mg/mL], 6 mcg/breath) QID during waking hours.
intervention type: Drug
intervention name: Inhaled treprostinil solution
description: Inhaled treprostinil solution per dose and schedule specified in the arm
arm group label: Inhaled Treprostinil Solution
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
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country: Israel
country: United States
responsible party type: Sponsor
mesh term: Lung Diseases
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Hypertension, Pulmonary
mesh term: Hypertension
mesh term: Treprostinil
sharing ipd: No