<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/NCT01670136</url>
  </required_header>
  <id_info>
    <org_study_id>11-1646</org_study_id>
    <secondary_id>HHSN27500014</secondary_id>
    <nct_id>NCT01670136</nct_id>
  </id_info>
  <brief_title>Pharmacokinetics of Sildenafil in Premature Infants</brief_title>
  <official_title>Pharmacokinetics of Sildenafil in Premature Infants</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of North Carolina, Chapel Hill</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Emmes Company, LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of North Carolina, Chapel Hill</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to learn more about the safety and dosing of sildenafil in&#xD;
      infants.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Pharmacokinetics and safety of sildenafil will be studied in preterm infants who are&#xD;
      receiving sildenafil per standard of care or 1 dose prescribed for the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>February 2013</start_date>
  <completion_date type="Actual">July 2016</completion_date>
  <primary_completion_date type="Actual">July 2016</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area under the plasma concentration versus time curve 0-24 hours for sildenafil</measure>
    <time_frame>IV study dose 0-15 min,1-2,3-4,12-14,24-30,48-56hr after flush.Clinical care: IV &lt;0.5hr before dose &lt;15 min &amp; 3-4hr after flush &lt;0.5hr before next dose. Enteral &lt;0.5hr before dose, 1-2 &amp; 3-4hr after dose, &lt;0.5hr before next dose. 22-26hr after last dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Peak plasma concentration of sildenafil</measure>
    <time_frame>IV study dose 0-15 min,1-2,3-4,12-14,24-30,48-56hr after flush.Clinical care: IV &lt;0.5hr before dose &lt;15 min &amp; 3-4hr after flush &lt;0.5hr before next dose. Enteral &lt;0.5hr before dose, 1-2 &amp; 3-4hr after dose, &lt;0.5hr before next dose. 22-26hr after last dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Clearance of sildenafil</measure>
    <time_frame>IV study dose 0-15 min,1-2,3-4,12-14,24-30,48-56hr after flush.Clinical care: IV &lt;0.5hr before dose &lt;15 min &amp; 3-4hr after flush &lt;0.5hr before next dose. Enteral &lt;0.5hr before dose, 1-2 &amp; 3-4hr after dose, &lt;0.5hr before next dose. 22-26hr after last dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Volume of distribution at steady state</measure>
    <time_frame>IV study dose 0-15 min,1-2,3-4,12-14,24-30,48-56hr after flush.Clinical care: IV &lt;0.5hr before dose &lt;15 min &amp; 3-4hr after flush &lt;0.5hr before next dose. Enteral &lt;0.5hr before dose, 1-2 &amp; 3-4hr after dose, &lt;0.5hr before next dose. 22-26hr after last dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Half life of sildenafil</measure>
    <time_frame>IV study dose 0-15 min,1-2,3-4,12-14,24-30,48-56hr after flush.Clinical care: IV &lt;0.5hr before dose &lt;15 min &amp; 3-4hr after flush &lt;0.5hr before next dose. Enteral &lt;0.5hr before dose, 1-2 &amp; 3-4hr after dose, &lt;0.5hr before next dose. 22-26hr after last dose</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with adverse events as a measure of safety and tolerability.</measure>
    <time_frame>From the time of the first dose to 3 days after the last dose; serious adverse events will be collected from the first dose of sildenafil to 7 days after the last dose of sildenafil</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between serum and dried blood spot samples</measure>
    <time_frame>1-7 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate P450 single nucleotide polymorphisms (SNPs)</measure>
    <time_frame>2-7 days</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>Persistent Pulmonary Hypertension of the Newborn</condition>
  <arm_group>
    <arm_group_label>sildenafil, standard of care</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Infants receiving sildenafil as standard of care</description>
  </arm_group>
  <arm_group>
    <arm_group_label>sildenafil administered for study</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>1 dose of sildenafil administered for study</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>1 dose of sildenafil</intervention_name>
    <description>A single IV dose of sildenafil will be administered over 90 minutes with no greater than a 15-minute flush. Final dose to be determined based on at least the first 4 participants enrolled in Cohort 1; final dose expected to be a single dose between 0.25 and 0.5 mg/kg.</description>
    <arm_group_label>sildenafil administered for study</arm_group_label>
    <other_name>Revatio</other_name>
    <other_name>Viagra</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Cohort 1:&#xD;
&#xD;
          -  Gestational age 28 weeks or less receiving sildenafil as standard of care &lt; 365&#xD;
             postnatal days&#xD;
&#xD;
        Cohort 2:&#xD;
&#xD;
          -  Gestational age 28 weeks or less&#xD;
&#xD;
          -  7-28 postnatal days of age&#xD;
&#xD;
          -  Mechanical ventilation or nasal continuous positive airway pressure (NCPAP) or&#xD;
             high-flow nasal cannula&#xD;
&#xD;
          -  Intravenous line in place&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Cohort 1:&#xD;
&#xD;
          -  Any condition that would make the participant, in the opinion of the investigator,&#xD;
             unsuitable for the study&#xD;
&#xD;
        Cohort 2:&#xD;
&#xD;
          -  Previous exposure to sildenafil within 7 days prior to enrollment&#xD;
&#xD;
          -  Any condition that would make the participant, in the opinion of the investigator,&#xD;
             unsuitable for the study&#xD;
&#xD;
          -  History of allergic reactions to sildenafil&#xD;
&#xD;
          -  AST &gt; ULN or ALT &gt; 3x ULN&#xD;
&#xD;
          -  Currently on a vasopressor for hypotension&#xD;
&#xD;
          -  Known sickle cell disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>364 Days</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Matthew M Laughon, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of North Carolina</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alabama at Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35249-7335</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Riley Hospital</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kosair Pediatric Research Unit</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</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>Kings County Hospital Center/SUNY Downstate Medical Center</name>
      <address>
        <city>Brooklyn</city>
        <state>New York</state>
        <zip>11203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of North Carolina</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cincinnati Children's Hospital Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</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_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>August 17, 2012</study_first_submitted>
  <study_first_submitted_qc>August 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 21, 2012</study_first_posted>
  <last_update_submitted>November 1, 2016</last_update_submitted>
  <last_update_submitted_qc>November 1, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 2, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>sildenafil</keyword>
  <keyword>preterm infants</keyword>
  <keyword>persistent pulmonary hypertension of the newborn</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension, Pulmonary</mesh_term>
    <mesh_term>Persistent Fetal Circulation Syndrome</mesh_term>
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sildenafil Citrate</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/NCT01670136
org study id: 11-1646
secondary id: HHSN27500014
nct id: NCT01670136
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The purpose of this study is to learn more about the safety and dosing of sildenafil in
      infants.
Pharmacokinetics and safety of sildenafil will be studied in preterm infants who are
      receiving sildenafil per standard of care or 1 dose prescribed for the study.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Area under the plasma concentration versus time curve 0-24 hours for sildenafil
time frame: IV study dose 0-15 min,1-2,3-4,12-14,24-30,48-56hr after flush.Clinical care: IV <0.5hr before dose <15 min & 3-4hr after flush <0.5hr before next dose. Enteral <0.5hr before dose, 1-2 & 3-4hr after dose, <0.5hr before next dose. 22-26hr after last dose
measure: Peak plasma concentration of sildenafil
time frame: IV study dose 0-15 min,1-2,3-4,12-14,24-30,48-56hr after flush.Clinical care: IV <0.5hr before dose <15 min & 3-4hr after flush <0.5hr before next dose. Enteral <0.5hr before dose, 1-2 & 3-4hr after dose, <0.5hr before next dose. 22-26hr after last dose
measure: Clearance of sildenafil
time frame: IV study dose 0-15 min,1-2,3-4,12-14,24-30,48-56hr after flush.Clinical care: IV <0.5hr before dose <15 min & 3-4hr after flush <0.5hr before next dose. Enteral <0.5hr before dose, 1-2 & 3-4hr after dose, <0.5hr before next dose. 22-26hr after last dose
measure: Volume of distribution at steady state
time frame: IV study dose 0-15 min,1-2,3-4,12-14,24-30,48-56hr after flush.Clinical care: IV <0.5hr before dose <15 min & 3-4hr after flush <0.5hr before next dose. Enteral <0.5hr before dose, 1-2 & 3-4hr after dose, <0.5hr before next dose. 22-26hr after last dose
measure: Half life of sildenafil
time frame: IV study dose 0-15 min,1-2,3-4,12-14,24-30,48-56hr after flush.Clinical care: IV <0.5hr before dose <15 min & 3-4hr after flush <0.5hr before next dose. Enteral <0.5hr before dose, 1-2 & 3-4hr after dose, <0.5hr before next dose. 22-26hr after last dose
measure: Number of subjects with adverse events as a measure of safety and tolerability.
time frame: From the time of the first dose to 3 days after the last dose; serious adverse events will be collected from the first dose of sildenafil to 7 days after the last dose of sildenafil
measure: Correlation between serum and dried blood spot samples
time frame: 1-7 days
measure: Evaluate P450 single nucleotide polymorphisms (SNPs)
time frame: 2-7 days
arm group label: sildenafil, standard of care
arm group type: No Intervention
description: Infants receiving sildenafil as standard of care
arm group label: sildenafil administered for study
arm group type: Other
description: 1 dose of sildenafil administered for study
intervention type: Drug
intervention name: 1 dose of sildenafil
description: A single IV dose of sildenafil will be administered over 90 minutes with no greater than a 15-minute flush. Final dose to be determined based on at least the first 4 participants enrolled in Cohort 1; final dose expected to be a single dose between 0.25 and 0.5 mg/kg.
arm group label: sildenafil administered for study
other name: Revatio
other name: Viagra
criteria: 
gender: All
minimum age: N/A
maximum age: 364 Days
healthy volunteers: No
last name: Matthew M Laughon, MD, MPH
role: Principal Investigator
affiliation: University of North Carolina
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Hypertension, Pulmonary
mesh term: Persistent Fetal Circulation Syndrome
mesh term: Hypertension
mesh term: Sildenafil Citrate
sharing ipd: No