<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/NCT02189122</url>
  </required_header>
  <id_info>
    <org_study_id>140707</org_study_id>
    <nct_id>NCT02189122</nct_id>
  </id_info>
  <brief_title>Comparative Effects of Aspirin and NHP-544C</brief_title>
  <official_title>Comparative Effects of Rapid-Release Aspirin and NHP-544C on Basal and Bradykinin Stimulated Prostacyclin Production</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderbilt University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Vanderbilt University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators will compare the effects of rapid release aspirin and NHP-544C on the&#xD;
      prostacyclin response to intravenous bradykinin.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">July 2015</completion_date>
  <primary_completion_date type="Actual">July 2015</primary_completion_date>
  <phase>N/A</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>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Urine Thromboxane Concentrations at Placebo ASA or Placebo NHP-544C Dose</measure>
    <time_frame>24 hour collection</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Urine Thromboxane Concentrations at 81mg ASA or NHP-544C Dose</measure>
    <time_frame>24 hour collection</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Urine Thromboxane Concentrations at 162.5 mg ASA or NHP-544C Dose</measure>
    <time_frame>24 hour collection</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Urine Prostacyclin Concentrations at Placebo ASA or Placebo NHP-544C Dose</measure>
    <time_frame>24 hour collection</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Urine Prostacyclin Concentrations at 81 mg ASA or NHP-544C Dose</measure>
    <time_frame>24 hour collection</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Urine Prostacyclin Concentrations at 162.5 mg ASA or NHP-544C Dose</measure>
    <time_frame>24 hour collection</time_frame>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">61</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Group 1:Aspirin/placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Group 1 will be randomized to the order in which they receive rapid-release aspirin (ASA), 81 mg), ASA 162.5 mg, and identical-appearing placebo for 5 days. Bradykinin will be given intravenously in graded doses on the fifth day of each treatment period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2:NHP-544C/placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Group 2 will be randomized to the order in which they receive NHP-544C 81 mg, NPH-544C 162.5 mg and identical-appearing placebo for five days. Bradykinin will be given intravenously in graded doses on the fifth day of each treatment period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bradykinin</intervention_name>
    <description>Bradykinin will be given intravenously in graded doses. Each dose will be given for 15 minutes.</description>
    <arm_group_label>Group 1:Aspirin/placebo</arm_group_label>
    <arm_group_label>Group 2:NHP-544C/placebo</arm_group_label>
    <other_name>BK</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aspirin 81 mg</intervention_name>
    <description>Subjects will take Aspirin 81 mg per day for five days.</description>
    <arm_group_label>Group 1:Aspirin/placebo</arm_group_label>
    <other_name>ASA 81 mg</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aspirin 162 mg</intervention_name>
    <description>Subjects will take aspirin 162 mg per day for 5 days.</description>
    <arm_group_label>Group 1:Aspirin/placebo</arm_group_label>
    <other_name>ASA 162 mg</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NHP544-C 81 mg</intervention_name>
    <description>Subjects will take NHP544C 81 mg per day for five days.</description>
    <arm_group_label>Group 2:NHP-544C/placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NHP544C 162 mg</intervention_name>
    <description>Subjects will take NHP544C 162 mg once a day for five days.</description>
    <arm_group_label>Group 2:NHP-544C/placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Subjects will take matching placebo for five days.</description>
    <arm_group_label>Group 1:Aspirin/placebo</arm_group_label>
    <arm_group_label>Group 2:NHP-544C/placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Ages of 18 and 55 years, inclusive&#xD;
&#xD;
          2. No significant medical issues without significant abnormal findings at the baseline&#xD;
             physical examination&#xD;
&#xD;
          3. Body mass index (BMI) between 18.0 and 30.0kg/m2 (weight (kg)/[height(m)]2)&#xD;
&#xD;
          4. For women - negative pregnancy test on Period 1, Day -1, or surgically sterilized, or&#xD;
             is at least two years post-menopausal prior to randomization. Females of childbearing&#xD;
             potential must be practicing an acceptable method of birth control to be eligible.&#xD;
             Acceptable forms of birth control include: condom plus spermicide or condom plus other&#xD;
             form of birth control including hormonal method (IUD, patch, ring, implant, or&#xD;
             injectable), sterilization of partner, or non-hormonal IUD. The use of oral&#xD;
             contraceptives is allowed during the study, but the subject must be on a stable dose&#xD;
             for 30 days prior to the trial and throughout all four dosing periods&#xD;
&#xD;
          5. Ability to understand the requirements of the study and a willingness to comply with&#xD;
             all study procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Clinically significant and relevant medical history (including failure of a major&#xD;
             organ system) or current medical illness, and is deemed by the Principal Investigator&#xD;
             to be unsuitable to participate in the study&#xD;
&#xD;
          2. Participation in an investigational drug study within the 30 days prior to CRC&#xD;
             admission&#xD;
&#xD;
          3. Use of aspirin or other NSAID within 14 days of Day 1 of the study. All other&#xD;
             medications, prescription (with the exception of contraceptives), over-the-counter&#xD;
             (OTC), herbal, and vitamin supplements must be discontinued 7 days prior to Day 1. If&#xD;
             subjects are taking prescription medication, or OTC medication at the direction of a&#xD;
             health care provider, that provider must confirm that it is acceptable for them to&#xD;
             stop dosing for the duration of the study&#xD;
&#xD;
          4. History of metabolic, renal, hepatic, hemorrhagic stroke, gastrointestinal bleed,&#xD;
             cardiovascular disease, central nervous system disorder, or peptic ulcer disease or&#xD;
             other chronic bleeding disorder&#xD;
&#xD;
          5. History of gastrointestinal disorder that could result in incomplete absorption of the&#xD;
             study drug&#xD;
&#xD;
          6. Malignancy, or neurologic or psychiatric disorder&#xD;
&#xD;
          7. Abnormal laboratory value(s) determined to be clinically significant (in the opinion&#xD;
             of the Investigator)&#xD;
&#xD;
          8. History of illicit drug abuse in the past year or current evidence of such abuse in&#xD;
             the opinion of the investigator&#xD;
&#xD;
          9. Pregnancy or lactation&#xD;
&#xD;
         10. Acute illness within 1 week of CRC admission&#xD;
&#xD;
         11. Significant loss of blood or blood or plasma donation within 30 days of drug&#xD;
             administration&#xD;
&#xD;
         12. Hypersensitivity or allergy to NSAIDs, aspirin, ethylcellulose, polyvidone, castor&#xD;
             oil, magnesium stearate, tartaric acid, colloidal anhydrous silica, talc, gelatin,&#xD;
             titanium dioxide, erythrosine, or indigotin&#xD;
&#xD;
         13. History of aspirin resistance&#xD;
&#xD;
         14. History of alcohol abuse within past year. Current alcohol use should not exceed 14&#xD;
             standard alcoholic drinks per week. A drink is defined as 1.5 ounces (oz.) liquor, 12&#xD;
             oz. beer, or 6 oz. wine&#xD;
&#xD;
         15. Alcohol consumption within 3 days of Day 1&#xD;
&#xD;
         16. Difficulty swallowing oral medications&#xD;
&#xD;
         17. Consumption of coffee or caffeine-containing beverages exceeding the equivalent of&#xD;
             five 8-oz cups of coffee per day on average&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nancy J Brown, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vanderbilt University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Gamboa JL, Devin JK, Ramirez CE, Yu C, Nian H, Lee RH, Brown NJ. Comparative effects of immediate-release and extended-release aspirin on basal and bradykinin-stimulated excretion of thromboxane and prostacyclin metabolites. Pharmacol Res Perspect. 2016 Feb 23;4(2):e00221. doi: 10.1002/prp2.221. eCollection 2016 Apr.</citation>
    <PMID>27069632</PMID>
  </results_reference>
  <verification_date>June 2016</verification_date>
  <study_first_submitted>July 10, 2014</study_first_submitted>
  <study_first_submitted_qc>July 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 14, 2014</study_first_posted>
  <results_first_submitted>March 18, 2016</results_first_submitted>
  <results_first_submitted_qc>April 26, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">June 3, 2016</results_first_posted>
  <last_update_submitted>June 3, 2016</last_update_submitted>
  <last_update_submitted_qc>June 3, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 12, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Vanderbilt University</investigator_affiliation>
    <investigator_full_name>Nancy J. Brown</investigator_full_name>
    <investigator_title>M.D.; Professor of Medicine and Pharmacology</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aspirin</mesh_term>
    <mesh_term>Bradykinin</mesh_term>
    <mesh_term>Kininogens</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Twenty-five enrolled participants were excluded prior to randomization to study group because they did not meet inclusion or exclusion criteria.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Group 1:Aspirin/Placebo</title>
          <description>Group 1 will be randomized to receive rapid release aspirin (ASA, 81 mg), ASA 162.5 mg, or identical-appearing placebo for 5 days. Bradykinin will be given intravenously in graded doses on the fifth day of study.&#xD;
Bradykinin: Bradykinin will be given intravenously in graded doses. Each dose will be given for 15 minutes.&#xD;
Aspirin 81 mg: Subjects will take Aspirin 81 mg per day for five days.&#xD;
Aspirin 162 mg: Subjects will take aspirin 162 mg per day for 5 days.&#xD;
Placebo: Subjects will take matching placebo for five days.&#xD;
Three subjects participated in each possible sequence with the following exceptions: Four subjects participated in the sequence Aspirin 81 mg, Aspirin 162.5 mg, placebo; two subjects participated in the sequence placebo, Aspirin 162.5 mg, Aspirin 81 mg.</description>
        </group>
        <group group_id="P2">
          <title>Group 2:NHP-544C/Placebo</title>
          <description>Group 2 will be randomized to receive NHP-544C 81 mg, NPH-544C 162.5 mg or placebo. Bradykinin will be given intravenously in graded doses on the fifth day of study drug.&#xD;
Bradykinin: Bradykinin will be given intravenously in graded doses. Each dose will be given for 15 minutes.&#xD;
NHP544-C 81 mg: Subjects will take NHP544C 81 mg per day for five days.&#xD;
NHP544C 162 mg: Subjects will take NHP544C 162 mg once a day for five days.&#xD;
Placebo: Subjects will take matching placebo for five days.&#xD;
Three subjects participated in each possible sequence with the following exceptions: Four subjects participated in the sequence NHP544C 81 mg, NHP544C 162 mg, placebo; two subjects participated in the sequence NHP544C 162 mg, placebo, NHP544C 81 mg.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Group 1:Aspirin/Placebo</title>
          <description>Group 1 will be randomized to receive rapid release aspirin (ASA, 81 mg), ASA 162.5 mg, or identical-appearing placebo for 5 days. Bradykinin will be given intravenously in graded doses on the fifth day of study.&#xD;
Bradykinin: Bradykinin will be given intravenously in graded doses. Each dose will be given for 15 minutes.&#xD;
Aspirin 81 mg: Subjects will take Aspirin 81 mg per day for five days.&#xD;
Aspirin 162 mg: Subjects will take aspirin 162 mg per day for 5 days.&#xD;
Placebo: Subjects will take matching placebo for five days.</description>
        </group>
        <group group_id="B2">
          <title>Group 2:NHP-544C/Placebo</title>
          <description>Group 2 will be randomized to receive NHP-544C 81 mg, NPH-544C 162.5 mg or placebo. Bradykinin will be given intravenously in graded doses on the fifth day of study drug.&#xD;
Bradykinin: Bradykinin will be given intravenously in graded doses. Each dose will be given for 15 minutes.&#xD;
NHP544-C 81 mg: Subjects will take NHP544C 81 mg per day for five days.&#xD;
NHP544C 162 mg: Subjects will take NHP544C 162 mg once a day for five days.&#xD;
Placebo: Subjects will take matching placebo for five days.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="18"/>
            <count group_id="B2" value="18"/>
            <count group_id="B3" value="36"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27.4" lower_limit="24.2" upper_limit="33.6"/>
                    <measurement group_id="B2" value="26.5" lower_limit="24.1" upper_limit="28.4"/>
                    <measurement group_id="B3" value="27.1" lower_limit="24.1" upper_limit="33.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>11-dehydrothromboxane B2</title>
          <units>ng/mg creatinine</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0.180" lower_limit="0.158" upper_limit=".240"/>
                    <measurement group_id="B2" value=".214" lower_limit=".191" upper_limit=".296"/>
                    <measurement group_id="B3" value=".206" lower_limit=".172" upper_limit=".272"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>2,3-dinor-6-keto-PGF1alpha</title>
          <units>ng/mg creatinine</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value=".1" lower_limit=".089" upper_limit=".139"/>
                    <measurement group_id="B2" value=".139" lower_limit=".117" upper_limit=".252"/>
                    <measurement group_id="B3" value=".121" lower_limit=".095" upper_limit=".158"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Urine Thromboxane Concentrations at Placebo ASA or Placebo NHP-544C Dose</title>
        <time_frame>24 hour collection</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Group 1:Aspirin/Placebo</title>
            <description>Group 1 will be randomized to the order in which they receive rapid-release aspirin (ASA), 81 mg), ASA 162.5 mg, and identical-appearing placebo for 5 days. Bradykinin will be given intravenously in graded doses on the fifth day of each treatment period.&#xD;
Bradykinin: Bradykinin will be given intravenously in graded doses. Each dose will be given for 15 minutes.&#xD;
Aspirin 81 mg: Subjects will take Aspirin 81 mg per day for five days.&#xD;
Aspirin 162 mg: Subjects will take aspirin 162 mg per day for 5 days.&#xD;
Placebo: Subjects will take matching placebo for five days.</description>
          </group>
          <group group_id="O2">
            <title>Group 2:NHP-544C/Placebo</title>
            <description>Group 2 will be randomized to the order in which they receive NHP-544C 81 mg, NPH-544C 162.5 mg and identical-appearing placebo for five days. Bradykinin will be given intravenously in graded doses on the fifth day of each treatment period.&#xD;
Bradykinin: Bradykinin will be given intravenously in graded doses. Each dose will be given for 15 minutes.&#xD;
NHP544-C 81 mg: Subjects will take NHP544C 81 mg per day for five days.&#xD;
NHP544C 162 mg: Subjects will take NHP544C 162 mg once a day for five days.&#xD;
Placebo: Subjects will take matching placebo for five days.</description>
          </group>
        </group_list>
        <measure>
          <title>Urine Thromboxane Concentrations at Placebo ASA or Placebo NHP-544C Dose</title>
          <units>ng/mg creatinine</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.181" lower_limit="0.143" upper_limit="0.216"/>
                    <measurement group_id="O2" value="0.255" lower_limit="0.219" upper_limit="0.322"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Urine Thromboxane Concentrations at 81mg ASA or NHP-544C Dose</title>
        <time_frame>24 hour collection</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Group 1:Aspirin/Placebo</title>
            <description>Group 1 will be randomized to the order in which they receive rapid-release aspirin (ASA), 81 mg), ASA 162.5 mg, and identical-appearing placebo for 5 days. Bradykinin will be given intravenously in graded doses on the fifth day of each treatment period.&#xD;
Bradykinin: Bradykinin will be given intravenously in graded doses. Each dose will be given for 15 minutes.&#xD;
Aspirin 81 mg: Subjects will take Aspirin 81 mg per day for five days.&#xD;
Aspirin 162 mg: Subjects will take aspirin 162 mg per day for 5 days.&#xD;
Placebo: Subjects will take matching placebo for five days.</description>
          </group>
          <group group_id="O2">
            <title>Group 2:NHP-544C/Placebo</title>
            <description>Group 2 will be randomized to the order in which they receive NHP-544C 81 mg, NPH-544C 162.5 mg and identical-appearing placebo for five days. Bradykinin will be given intravenously in graded doses on the fifth day of each treatment period.&#xD;
Bradykinin: Bradykinin will be given intravenously in graded doses. Each dose will be given for 15 minutes.&#xD;
NHP544-C 81 mg: Subjects will take NHP544C 81 mg per day for five days.&#xD;
NHP544C 162 mg: Subjects will take NHP544C 162 mg once a day for five days.&#xD;
Placebo: Subjects will take matching placebo for five days.</description>
          </group>
        </group_list>
        <measure>
          <title>Urine Thromboxane Concentrations at 81mg ASA or NHP-544C Dose</title>
          <units>ng/mg creatinine</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0685" lower_limit="0.0585" upper_limit="0.0717"/>
                    <measurement group_id="O2" value="0.115" lower_limit="0.095" upper_limit="0.155"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Urine Thromboxane Concentrations at 162.5 mg ASA or NHP-544C Dose</title>
        <time_frame>24 hour collection</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Group 1:Aspirin/Placebo</title>
            <description>Group 1 will be randomized to receive rapid release aspirin (ASA, 81 mg), ASA 162.5 mg, or identical-appearing placebo for 5 days. Bradykinin will be given intravenously in graded doses on the fifth day of study.&#xD;
Bradykinin: Bradykinin will be given intravenously in graded doses. Each dose will be given for 15 minutes.&#xD;
Aspirin 81 mg: Subjects will take Aspirin 81 mg per day for five days.&#xD;
Aspirin 162 mg: Subjects will take aspirin 162 mg per day for 5 days.&#xD;
Placebo: Subjects will take matching placebo for five days.</description>
          </group>
          <group group_id="O2">
            <title>Group 2:NHP-544C/Placebo</title>
            <description>Group 2 will be randomized to receive NHP-544C 81 mg, NPH-544C 162.5 mg or placebo. Bradykinin will be given intravenously in graded doses on the fifth day of study drug.&#xD;
Bradykinin: Bradykinin will be given intravenously in graded doses. Each dose will be given for 15 minutes.&#xD;
NHP544-C 81 mg: Subjects will take NHP544C 81 mg per day for five days.&#xD;
NHP544C 162 mg: Subjects will take NHP544C 162 mg once a day for five days.&#xD;
Placebo: Subjects will take matching placebo for five days.</description>
          </group>
        </group_list>
        <measure>
          <title>Urine Thromboxane Concentrations at 162.5 mg ASA or NHP-544C Dose</title>
          <units>ng/mg creatinine</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.054" lower_limit="0.043" upper_limit="0.077"/>
                    <measurement group_id="O2" value="0.071" lower_limit="0.056" upper_limit="0.115"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Urine Prostacyclin Concentrations at Placebo ASA or Placebo NHP-544C Dose</title>
        <time_frame>24 hour collection</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Group 1:Aspirin/Placebo</title>
            <description>Group 1 will be randomized to the order in which they receive rapid-release aspirin (ASA), 81 mg), ASA 162.5 mg, and identical-appearing placebo for 5 days. Bradykinin will be given intravenously in graded doses on the fifth day of each treatment period.&#xD;
Bradykinin: Bradykinin will be given intravenously in graded doses. Each dose will be given for 15 minutes.&#xD;
Aspirin 81 mg: Subjects will take Aspirin 81 mg per day for five days.&#xD;
Aspirin 162 mg: Subjects will take aspirin 162 mg per day for 5 days.&#xD;
Placebo: Subjects will take matching placebo for five days.</description>
          </group>
          <group group_id="O2">
            <title>Group 2:NHP-544C/Placebo</title>
            <description>Group 2 will be randomized to the order in which they receive NHP-544C 81 mg, NPH-544C 162.5 mg and identical-appearing placebo for five days. Bradykinin will be given intravenously in graded doses on the fifth day of each treatment period.&#xD;
Bradykinin: Bradykinin will be given intravenously in graded doses. Each dose will be given for 15 minutes.&#xD;
NHP544-C 81 mg: Subjects will take NHP544C 81 mg per day for five days.&#xD;
NHP544C 162 mg: Subjects will take NHP544C 162 mg once a day for five days.&#xD;
Placebo: Subjects will take matching placebo for five days.</description>
          </group>
        </group_list>
        <measure>
          <title>Urine Prostacyclin Concentrations at Placebo ASA or Placebo NHP-544C Dose</title>
          <units>ng/mg creatinine</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.102" lower_limit="0.083" upper_limit="0.116"/>
                    <measurement group_id="O2" value="0.144" lower_limit="0.128" upper_limit="0.194"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Urine Prostacyclin Concentrations at 81 mg ASA or NHP-544C Dose</title>
        <time_frame>24 hour collection</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Group 1:Aspirin/Placebo</title>
            <description>Group 1 will be randomized to the order in which they receive rapid-release aspirin (ASA), 81 mg), ASA 162.5 mg, and identical-appearing placebo for 5 days. Bradykinin will be given intravenously in graded doses on the fifth day of each treatment period.&#xD;
Bradykinin: Bradykinin will be given intravenously in graded doses. Each dose will be given for 15 minutes.&#xD;
Aspirin 81 mg: Subjects will take Aspirin 81 mg per day for five days.&#xD;
Aspirin 162 mg: Subjects will take aspirin 162 mg per day for 5 days.&#xD;
Placebo: Subjects will take matching placebo for five days.</description>
          </group>
          <group group_id="O2">
            <title>Group 2:NHP-544C/Placebo</title>
            <description>Group 2 will be randomized to the order in which they receive NHP-544C 81 mg, NPH-544C 162.5 mg and identical-appearing placebo for five days. Bradykinin will be given intravenously in graded doses on the fifth day of each treatment period.&#xD;
Bradykinin: Bradykinin will be given intravenously in graded doses. Each dose will be given for 15 minutes.&#xD;
NHP544-C 81 mg: Subjects will take NHP544C 81 mg per day for five days.&#xD;
NHP544C 162 mg: Subjects will take NHP544C 162 mg once a day for five days.&#xD;
Placebo: Subjects will take matching placebo for five days.</description>
          </group>
        </group_list>
        <measure>
          <title>Urine Prostacyclin Concentrations at 81 mg ASA or NHP-544C Dose</title>
          <units>ng/mg creatinine</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.069" lower_limit="0.049" upper_limit="0.116"/>
                    <measurement group_id="O2" value="0.128" lower_limit="0.105" upper_limit="0.161"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Urine Prostacyclin Concentrations at 162.5 mg ASA or NHP-544C Dose</title>
        <time_frame>24 hour collection</time_frame>
        <population>Data are given for 162.5 mg study day</population>
        <group_list>
          <group group_id="O1">
            <title>Group 1:Aspirin/Placebo</title>
            <description>Group 1 will be randomized to receive rapid release aspirin (ASA, 81 mg), ASA 162.5 mg, or identical-appearing placebo for 5 days. Bradykinin will be given intravenously in graded doses on the fifth day of study.&#xD;
Bradykinin: Bradykinin will be given intravenously in graded doses. Each dose will be given for 15 minutes.&#xD;
Aspirin 81 mg: Subjects will take Aspirin 81 mg per day for five days.&#xD;
Aspirin 162 mg: Subjects will take aspirin 162 mg per day for 5 days.&#xD;
Placebo: Subjects will take matching placebo for five days.</description>
          </group>
          <group group_id="O2">
            <title>Group 2:NHP-544C/Placebo</title>
            <description>Group 2 will be randomized to receive NHP-544C 81 mg, NPH-544C 162.5 mg or placebo. Bradykinin will be given intravenously in graded doses on the fifth day of study drug.&#xD;
Bradykinin: Bradykinin will be given intravenously in graded doses. Each dose will be given for 15 minutes.&#xD;
NHP544-C 81 mg: Subjects will take NHP544C 81 mg per day for five days.&#xD;
NHP544C 162 mg: Subjects will take NHP544C 162 mg once a day for five days.&#xD;
Placebo: Subjects will take matching placebo for five days.</description>
          </group>
        </group_list>
        <measure>
          <title>Urine Prostacyclin Concentrations at 162.5 mg ASA or NHP-544C Dose</title>
          <population>Data are given for 162.5 mg study day</population>
          <units>ng/mg creatinine</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.067" lower_limit="0.045" upper_limit="0.104"/>
                    <measurement group_id="O2" value="0.108" lower_limit="0.084" upper_limit="0.160"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Group 1:Aspirin/Placebo</title>
          <description>Group 1 will be randomized to receive rapid release aspirin (ASA, 81 mg), ASA 162.5 mg, or identical-appearing placebo for 5 days. Bradykinin will be given intravenously in graded doses on the fifth day of study.&#xD;
Bradykinin: Bradykinin will be given intravenously in graded doses. Each dose will be given for 15 minutes.&#xD;
Aspirin 81 mg: Subjects will take Aspirin 81 mg per day for five days.&#xD;
Aspirin 162 mg: Subjects will take aspirin 162 mg per day for 5 days.&#xD;
Placebo: Subjects will take matching placebo for five days.</description>
        </group>
        <group group_id="E2">
          <title>Group 2:NHP-544C/Placebo</title>
          <description>Group 2 will be randomized to receive NHP-544C 81 mg, NPH-544C 162.5 mg or placebo. Bradykinin will be given intravenously in graded doses on the fifth day of study drug.&#xD;
Bradykinin: Bradykinin will be given intravenously in graded doses. Each dose will be given for 15 minutes.&#xD;
NHP544-C 81 mg: Subjects will take NHP544C 81 mg per day for five days.&#xD;
NHP544C 162 mg: Subjects will take NHP544C 162 mg once a day for five days.&#xD;
Placebo: Subjects will take matching placebo for five days.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>ST T wave changes following bradykinin infusion</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>low albumin</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus or nasal congestion</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Nancy J. Brown, M.D.</name_or_title>
      <organization>VANDERBILT UNIVERSITY MEDICAL CENTER</organization>
      <phone>6153438701</phone>
      <email>nancy.j.brown@vanderbilt.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02189122
org study id: 140707
nct id: NCT02189122
lead sponsor: 
has dmc: Yes
The investigators will compare the effects of rapid release aspirin and NHP-544C on the
      prostacyclin response to intravenous bradykinin.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Urine Thromboxane Concentrations at Placebo ASA or Placebo NHP-544C Dose
time frame: 24 hour collection
measure: Urine Thromboxane Concentrations at 81mg ASA or NHP-544C Dose
time frame: 24 hour collection
measure: Urine Thromboxane Concentrations at 162.5 mg ASA or NHP-544C Dose
time frame: 24 hour collection
measure: Urine Prostacyclin Concentrations at Placebo ASA or Placebo NHP-544C Dose
time frame: 24 hour collection
measure: Urine Prostacyclin Concentrations at 81 mg ASA or NHP-544C Dose
time frame: 24 hour collection
measure: Urine Prostacyclin Concentrations at 162.5 mg ASA or NHP-544C Dose
time frame: 24 hour collection
arm group label: Group 1:Aspirin/placebo
arm group type: Active Comparator
description: Group 1 will be randomized to the order in which they receive rapid-release aspirin (ASA), 81 mg), ASA 162.5 mg, and identical-appearing placebo for 5 days. Bradykinin will be given intravenously in graded doses on the fifth day of each treatment period.
arm group label: Group 2:NHP-544C/placebo
arm group type: Active Comparator
description: Group 2 will be randomized to the order in which they receive NHP-544C 81 mg, NPH-544C 162.5 mg and identical-appearing placebo for five days. Bradykinin will be given intravenously in graded doses on the fifth day of each treatment period.
intervention type: Drug
intervention name: Bradykinin
description: Bradykinin will be given intravenously in graded doses. Each dose will be given for 15 minutes.
arm group label: Group 1:Aspirin/placebo
arm group label: Group 2:NHP-544C/placebo
other name: BK
intervention type: Drug
intervention name: Aspirin 81 mg
description: Subjects will take Aspirin 81 mg per day for five days.
arm group label: Group 1:Aspirin/placebo
other name: ASA 81 mg
intervention type: Drug
intervention name: Aspirin 162 mg
description: Subjects will take aspirin 162 mg per day for 5 days.
arm group label: Group 1:Aspirin/placebo
other name: ASA 162 mg
intervention type: Drug
intervention name: NHP544-C 81 mg
description: Subjects will take NHP544C 81 mg per day for five days.
arm group label: Group 2:NHP-544C/placebo
intervention type: Drug
intervention name: NHP544C 162 mg
description: Subjects will take NHP544C 162 mg once a day for five days.
arm group label: Group 2:NHP-544C/placebo
intervention type: Drug
intervention name: Placebo
description: Subjects will take matching placebo for five days.
arm group label: Group 1:Aspirin/placebo
arm group label: Group 2:NHP-544C/placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Nancy J Brown, MD
role: Principal Investigator
affiliation: Vanderbilt University Medical Center
facility: 
country: United States
citation: Gamboa JL, Devin JK, Ramirez CE, Yu C, Nian H, Lee RH, Brown NJ. Comparative effects of immediate-release and extended-release aspirin on basal and bradykinin-stimulated excretion of thromboxane and prostacyclin metabolites. Pharmacol Res Perspect. 2016 Feb 23;4(2):e00221. doi: 10.1002/prp2.221. eCollection 2016 Apr.
PMID: 27069632
responsible party type: Principal Investigator
investigator affiliation: Vanderbilt University
investigator full name: Nancy J. Brown
investigator title: M.D.; Professor of Medicine and Pharmacology
mesh term: Aspirin
mesh term: Bradykinin
mesh term: Kininogens
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 