<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/NCT01725269</url>
  </required_header>
  <id_info>
    <org_study_id>AIR001-CS06</org_study_id>
    <nct_id>NCT01725269</nct_id>
  </id_info>
  <brief_title>Long-term Study of AIR001 in Subjects With WHO Group 1 Pulmonary Arterial Hypertension Who Completed AIR001-CS05</brief_title>
  <official_title>A Phase 2, Multicenter, Open-Label Study to Evaluate the Intermediate/Long Term Safety and Efficacy of AIR001 in Subjects With WHO Group 1 Pulmonary Arterial Hypertension</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Aires Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Aires Pharmaceuticals, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The AIR001-CS05 study evaluated the safety and efficacy (effectiveness) of AIR001 over 16&#xD;
      weeks in subjects who have PAH. The purpose of the AIR001-CS06 study is to evaluate the&#xD;
      intermediate / long-term safety of AIR001 in subjects who have completed the AIR001-CS05&#xD;
      study. Assessments to evaluate the effectiveness of the study drug will include measurements&#xD;
      of exercise ability and evaluations of PAH disease symptoms.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary objective of this study is to evaluate the intermediate/long-term safety of&#xD;
      inhaled nebulized AIR001 administered according to 3 treatment arms (80 milligrams (mg) 4&#xD;
      times daily, 46 mg 4 times daily, or 80 mg once daily) in subjects with World Health&#xD;
      Organization (WHO) Group 1 Pulmonary Arterial Hypertension (PAH) who have completed the&#xD;
      16-week AIR001-CS05 study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Terminated early dt acquisition of Sponsor and change in corporate priorities&#xD;
  </why_stopped>
  <start_date>March 2013</start_date>
  <completion_date type="Actual">April 2014</completion_date>
  <primary_completion_date type="Actual">April 2014</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To evaluate the intermediate/long-term safety of inhaled nebulized AIR001</measure>
    <time_frame>minimum of 6 months</time_frame>
    <description>The primary objective of this study is to evaluate the intermediate/long-term safety of inhaled nebulized AIR001 administered according to 3 treatment arms (80 milligrams (mg) 4 times daily, 46 mg 4 times daily, or 80 mg once daily) in subjects with World Health Organization (WHO) Group 1 Pulmonary Arterial Hypertension (PAH) who have completed the 16-week AIR001-CS05 study.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To assess the effect of inhaled AIR001 on Time to Clinical Worsening, 6MWD, Functional Class, and Quality of Life</measure>
    <time_frame>minimum of 6 months</time_frame>
    <description>The secondary objectives of this study are to evaluate the effect of inhaled nebulized AIR001 administered according to 3 different treatment arms (80 mg 4 times daily, 46 mg 4 times daily, or 80 mg once daily) in subjects with WHO Group 1 PAH who completed the 16-week AIR001-CS05 study, as determined by time to the first morbidity/mortality event as defined in Time to Clinical Worsening (TTCW) assessments and by change from Baseline in AIR001-CS05 to the 40th week from the start of AIR001 nebulization in AIR001-CS05 (Week 24 of AIR001-CS06) and End of Study (EOS) or Termination visit of AIR001-CS06 in the following:6-Minute Walk Distance (6MWD) assessed at peak, WHO/NYHA Functional Class, Quality of Life (QOL) as measured by SF-36,Borg Dyspnea Index,6MWD assessed at trough</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">17</enrollment>
  <condition>Pulmonary Arterial Hypertension</condition>
  <arm_group>
    <arm_group_label>80mg AIR001, nebulized four times daily</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>AIR001, 80 mg into nebulizer</description>
  </arm_group>
  <arm_group>
    <arm_group_label>46 mg AIR001, nebulized four times daily</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>AIR001, 46 mg into nebulizer</description>
  </arm_group>
  <arm_group>
    <arm_group_label>80mg AIR001, nebulized once daily</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>AIR001, 80 mg into nebulizer</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AIR001</intervention_name>
    <description>All doses specified are the amount loaded into the I-neb AAD System nebulizer.</description>
    <arm_group_label>46 mg AIR001, nebulized four times daily</arm_group_label>
    <arm_group_label>80mg AIR001, nebulized four times daily</arm_group_label>
    <arm_group_label>80mg AIR001, nebulized once daily</arm_group_label>
    <other_name>(sodium nitrite inhalation soution)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Evidence of a personally signed and dated informed consent document indicating that&#xD;
             the subject (or a legally acceptable representative) has been informed of all&#xD;
             pertinent aspects of the study prior to initiation of any subject-mandated procedures.&#xD;
&#xD;
          2. Is willing and able to comply with scheduled visits, treatment plan, laboratory tests,&#xD;
             and other study procedures.&#xD;
&#xD;
          3. Has completed the 16-week AIR001-CS05study as planned.&#xD;
&#xD;
          4. If on corticosteroids, has been receiving a stable dose of less than or equal to 20&#xD;
             mg/day of prednisone (or equivalent dose, if other corticosteroid) for at least 1&#xD;
             month (30 days) prior to the AIR001-CS05 study Baseline/Day 1 visit. If receiving&#xD;
             treatment for Connective Tissue Disease (CTD) with any other drugs, doses should&#xD;
             remain stable, if clinically feasible, for the duration of the AIR001-CS06 study.&#xD;
&#xD;
          5. Women of childbearing potential must be using at least one form of medically&#xD;
             acceptable contraception (i.e. either oral, topical, implanted hormonal&#xD;
             contraceptives, or an intrauterine device) or two barrier methods; have a negative&#xD;
             pregnancy test at Screening and Baseline/Day 1 and agree to use reliable methods of&#xD;
             contraception until at least 24-hours after the last dose of study drug. Women who are&#xD;
             surgically sterile (i.e. hysterectomy, bilateral oophorectomy, or tubal ligation) or&#xD;
             those who are post-menopausal for at least 2 years are not considered to be of&#xD;
             childbearing potential. Men who are not sterile (i.e. have not had a vasectomy) must&#xD;
             also agree to use contraception until at least 24-hours after the last dose of study&#xD;
             drug.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Participation in a device or other interventional clinical studies (other than&#xD;
             AIR001-CS05), within 1 month (30 days) of Baseline/Day 1 and/or during study&#xD;
             participation.&#xD;
&#xD;
          2. Has uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure&#xD;
             &gt; 160 mmHg or sitting diastolic blood pressure &gt; 100 mmHg during Baseline/Day 1 visit.&#xD;
&#xD;
          3. Systolic blood pressure &lt; 90 mmHg at Baseline/Day 1.&#xD;
&#xD;
          4. Diagnosis of Down syndrome.&#xD;
&#xD;
          5. Moderate to severe hepatic impairment classified as a Child-Pugh Class B or C at&#xD;
             Baseline/Day 1.&#xD;
&#xD;
          6. Has chronic renal insufficiency as defined by serum creatinine &gt; 2.5 mg/dL or has an&#xD;
             estimated Glomerular Filtration Rate (eGFR) &lt; 30 mL/min at Baseline/Day 1, or requires&#xD;
             dialytic support.&#xD;
&#xD;
          7. Has a hemoglobin (Hgb) concentration &lt; 8.5 g/dL at Baseline/Day 1.&#xD;
&#xD;
          8. Personal or family history of the following:&#xD;
&#xD;
               1. Congenital or acquired methemoglobinemia;&#xD;
&#xD;
               2. RBC CYPB5 reductase deficiency.&#xD;
&#xD;
          9. History of glucose-6-phosphate dehydrogenase (G6PD) deficiency or any contraindication&#xD;
             to receiving methylene blue.&#xD;
&#xD;
         10. For subjects with Human immunodeficiency virus (HIV) associated PAH, requirement for&#xD;
             the use of inhaled pentamidine.&#xD;
&#xD;
         11. The use of oral or topical nitrates (nitroglycerin, glyceryl trinitrate (GTN),&#xD;
             isosorbide dinitrate, and isosorbide mononitrate) within 1 month (30 days) prior to&#xD;
             Baseline/Day 1 or throughout the AIR001-CS06 study until EOS or Termination visit.&#xD;
             Note: Intravenous GTN in an emergency setting may be administered by starting with a&#xD;
             low dose and titrating upward, while the subject is being monitored closely for&#xD;
             changes in blood pressure and heart rate.&#xD;
&#xD;
         12. Known or suspected hypersensitivity or allergic reaction to sodium nitrite or sodium&#xD;
             nitrate.&#xD;
&#xD;
         13. History of malignancy within 5-years prior to Baseline/Day 1 of the AIR001-CS05 study,&#xD;
             with the exception of localized non-metastatic basal cell carcinoma of the skin and in&#xD;
             situ carcinoma of the cervix.&#xD;
&#xD;
         14. Other severe acute or chronic medical or laboratory abnormality that may increase the&#xD;
             risk associated with study participation or investigational product administration or&#xD;
             may interfere with the interpretation of study results and, in the judgment of the&#xD;
             investigator, would make the subject inappropriate for entry into this study.&#xD;
&#xD;
         15. Has a psychiatric, addictive or other disorder that compromises the ability to give&#xD;
             informed consent for participating in this study. This includes subjects with a recent&#xD;
             history of abusing alcohol or illicit drugs 1 month (30 days) prior to study&#xD;
             Baseline/Day 1 of the AIR001-CS05 study and for the duration of the study.&#xD;
&#xD;
         16. Is currently pregnant or breastfeeding or intends to become pregnant during the&#xD;
             duration of the study.&#xD;
&#xD;
         17. Investigators, study staff or their immediate families.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Adaani E Frost, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Baylor College of Medicine, Houston</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UCSD Medical Center</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92037</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCLA Medical Center</name>
      <address>
        <city>Torrance</city>
        <state>California</state>
        <zip>90509</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Denver</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</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>Tufts Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02111</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>Boston University School of Medicine</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>St. Louis</city>
        <state>Missouri</state>
        <zip>63110-1093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45267</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ohio State University Medical Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</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>University of Texas Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Adaani Frost, M.D.</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</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>Aurora St. Luke's Medical Center</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Vincent's Hospital</name>
      <address>
        <city>Darlinghurst</city>
        <state>New South Wales</state>
        <zip>2010</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Prince Charles Hospital</name>
      <address>
        <city>Chermside</city>
        <state>Queensland</state>
        <zip>4032</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Hobart Hospital</name>
      <address>
        <city>Hobart</city>
        <state>Tasmania</state>
        <zip>7000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Alfred Hospital</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3004</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gottsegen Gyorgy Hungarian</name>
      <address>
        <city>Budapest</city>
        <zip>1083</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Semmelweis University</name>
      <address>
        <city>Budapest</city>
        <zip>1125</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Debrecen</name>
      <address>
        <city>Debrecen</city>
        <zip>4012</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Szeged</name>
      <address>
        <city>Szeged</city>
        <zip>6720</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Hungary</country>
    <country>United States</country>
  </location_countries>
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  <verification_date>April 2014</verification_date>
  <study_first_submitted>November 8, 2012</study_first_submitted>
  <study_first_submitted_qc>November 8, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 12, 2012</study_first_posted>
  <last_update_submitted>April 7, 2014</last_update_submitted>
  <last_update_submitted_qc>April 7, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 9, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>AIR001</keyword>
  <keyword>sodium nitrite</keyword>
  <keyword>PAH</keyword>
  <keyword>Pulmonary Arterial Hypertension</keyword>
  <keyword>inhaled sodium nitrite</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pulmonary Arterial Hypertension</mesh_term>
    <mesh_term>Familial Primary Pulmonary Hypertension</mesh_term>
    <mesh_term>Hypertension</mesh_term>
  </condition_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/NCT01725269
org study id: AIR001-CS06
nct id: NCT01725269
lead sponsor: 
has dmc: Yes
The AIR001-CS05 study evaluated the safety and efficacy (effectiveness) of AIR001 over 16
      weeks in subjects who have PAH. The purpose of the AIR001-CS06 study is to evaluate the
      intermediate / long-term safety of AIR001 in subjects who have completed the AIR001-CS05
      study. Assessments to evaluate the effectiveness of the study drug will include measurements
      of exercise ability and evaluations of PAH disease symptoms.
The primary objective of this study is to evaluate the intermediate/long-term safety of
      inhaled nebulized AIR001 administered according to 3 treatment arms (80 milligrams (mg) 4
      times daily, 46 mg 4 times daily, or 80 mg once daily) in subjects with World Health
      Organization (WHO) Group 1 Pulmonary Arterial Hypertension (PAH) who have completed the
      16-week AIR001-CS05 study.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: To evaluate the intermediate/long-term safety of inhaled nebulized AIR001
time frame: minimum of 6 months
description: The primary objective of this study is to evaluate the intermediate/long-term safety of inhaled nebulized AIR001 administered according to 3 treatment arms (80 milligrams (mg) 4 times daily, 46 mg 4 times daily, or 80 mg once daily) in subjects with World Health Organization (WHO) Group 1 Pulmonary Arterial Hypertension (PAH) who have completed the 16-week AIR001-CS05 study.
measure: To assess the effect of inhaled AIR001 on Time to Clinical Worsening, 6MWD, Functional Class, and Quality of Life
time frame: minimum of 6 months
description: The secondary objectives of this study are to evaluate the effect of inhaled nebulized AIR001 administered according to 3 different treatment arms (80 mg 4 times daily, 46 mg 4 times daily, or 80 mg once daily) in subjects with WHO Group 1 PAH who completed the 16-week AIR001-CS05 study, as determined by time to the first morbidity/mortality event as defined in Time to Clinical Worsening (TTCW) assessments and by change from Baseline in AIR001-CS05 to the 40th week from the start of AIR001 nebulization in AIR001-CS05 (Week 24 of AIR001-CS06) and End of Study (EOS) or Termination visit of AIR001-CS06 in the following:6-Minute Walk Distance (6MWD) assessed at peak, WHO/NYHA Functional Class, Quality of Life (QOL) as measured by SF-36,Borg Dyspnea Index,6MWD assessed at trough
arm group label: 80mg AIR001, nebulized four times daily
arm group type: Experimental
description: AIR001, 80 mg into nebulizer
arm group label: 46 mg AIR001, nebulized four times daily
arm group type: Experimental
description: AIR001, 46 mg into nebulizer
arm group label: 80mg AIR001, nebulized once daily
arm group type: Experimental
description: AIR001, 80 mg into nebulizer
intervention type: Drug
intervention name: AIR001
description: All doses specified are the amount loaded into the I-neb AAD System nebulizer.
arm group label: 46 mg AIR001, nebulized four times daily
arm group label: 80mg AIR001, nebulized four times daily
arm group label: 80mg AIR001, nebulized once daily
other name: (sodium nitrite inhalation soution)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Adaani E Frost, M.D.
role: Principal Investigator
affiliation: Baylor College of Medicine, Houston
facility: 
facility: 
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country: Australia
country: Hungary
country: United States
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responsible party type: Sponsor
mesh term: Pulmonary Arterial Hypertension
mesh term: Familial Primary Pulmonary Hypertension
mesh term: Hypertension