<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/NCT02206100</url>
  </required_header>
  <id_info>
    <org_study_id>PER977-01-003</org_study_id>
    <nct_id>NCT02206100</nct_id>
  </id_info>
  <brief_title>PK and PD of Single, Escalating Doses of PER977 Following Enoxaparin</brief_title>
  <acronym>PER977</acronym>
  <official_title>Phase I/II Evaluation of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects of Single, Hourly-Repeating, Escalating Doses of PER977 Following a Single Subcutaneous Dose of Enoxaparin</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Perosphere Pharmaceuticals Inc, a wholly owned subsidiary of AMAG Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AMAG Pharmaceuticals, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      PER977 administration following a single dose of enoxaparin&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Single escalating doses of PER977 from 100 to 300 mg, of 25 mg PER977 x 4 doses will be&#xD;
      administered following administration of enoxaparin. Serial pharmacokinetic and&#xD;
      pharmacodynamic assessments ( whole blood clotting time) will be performed. Adverse events&#xD;
      will be monitored.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>April 2014</start_date>
  <completion_date type="Actual">August 2014</completion_date>
  <primary_completion_date type="Actual">August 2014</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of adverse events</measure>
    <time_frame>1 day</time_frame>
    <description>Assessment of the number of subjects who experience adverse events and the number and type of adverse events</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Reversal of enoxaparin anticoagulation</measure>
    <time_frame>1 day</time_frame>
    <description>Measurement of the degree of change in whole blood clotting time and the proportion of subjects who achieve complete or partial reversal of anticoagulation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of enoxaparin</measure>
    <time_frame>1 day</time_frame>
    <description>Measurement of the pharmacokinetic characteristics of enoxaparin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of PER977 and its metabolite</measure>
    <time_frame>2 days</time_frame>
    <description>Measurement of the pharmacokinetic characteristics of PER977 and its metabolite</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>100 mg PER977 (10 subjects); the dose may be repeated two (2) times after an approximate one (1) hour interval for a maximum total of three (3) doses</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>200 mg PER977 (10 subjects); the dose may be repeated once at approximately one hour for a maximum total of two (2) doses</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>300 mg PER977 (10 subjects); the dose may be repeated once at approximately one hour after the initial dose for a maximum of total of two (2) doses</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 x 25 mg PER977 (10 subjects); study drug will be administered every 30 minutes for a total of 4 doses (cumulative dose of 100 mg PER977)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PER977</intervention_name>
    <description>reversal of edoxaban-induced anticoagulation</description>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_label>Cohort 4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Reversal of edoxaban-induced anticoagulation</description>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_label>Cohort 4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>enoxaparin</intervention_name>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_label>Cohort 4</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          1. Adults age 18 to 65 years, inclusive&#xD;
&#xD;
          2. Laboratory values have no clinically significant abnormalities&#xD;
&#xD;
          3. No clinically significant findings on 12-lead electrocardiogram&#xD;
&#xD;
          4. Body mass index (BMI) 18 to ≤ 27 kg/m2, inclusive&#xD;
&#xD;
          5. Male subjects agree to use appropriate contraception&#xD;
&#xD;
          6. Female subjects may be surgically sterile or post-menopausal or, if of child-bearing&#xD;
             potential, must have a negative serum pregnancy test prior to enrollment, and must&#xD;
             agree to use two forms of acceptable contraception for the duration of the study and&#xD;
             for a minimum of one complete menstrual cycles or 28 days following discharge from the&#xD;
             study.&#xD;
&#xD;
          7. Subjects must understand and agree to comply with the requirements of the study and&#xD;
             they must be willing to sign the informed consent form indicating voluntary consent to&#xD;
             participate in the study prior to initiation of screening or study related activities.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History or current evidence of clinically significant disease. Current evidence of&#xD;
             liver function tests or renal function tests greater than the upper limit of normal.&#xD;
             The presence of Gilbert's Syndrome is acceptable. Current evidence of QTcF &gt; normal&#xD;
             (450±10 msec for males or 470±10 msec for females).&#xD;
&#xD;
          2. History of unexplained syncope&#xD;
&#xD;
          3. Hypersensitivity to enoxaparin sodium, thrombocytopenia with a positive in vitro test&#xD;
             to anti-platelet antibody in the presence of enoxaparin sodium, hypersensitivity to&#xD;
             heparin or porcine products or any other contraindication to enoxaparin&#xD;
&#xD;
          4. History of major bleeding, trauma, surgical procedure of any type, or vaginal delivery&#xD;
             within six months prior to screening&#xD;
&#xD;
          5. History of peptic ulcer, gastrointestinal bleeding or bleeding from hemorrhoids within&#xD;
             six months prior to screening&#xD;
&#xD;
          6. History of minor bleeding episodes such as epistaxis, or gingival bleeding within 1&#xD;
             month prior to screening&#xD;
&#xD;
          7. Personal or family history of clotting disorder or abnormality, excessive bleeding,&#xD;
             thrombovascular disease or any hematologic disorder involving platelets or clotting&#xD;
             abnormalities or any condition requiring treatment with transfusions, or personal&#xD;
             history of heparin-induced thrombocytopenia&#xD;
&#xD;
          8. Females with a history of dysfunctional uterine bleeding who have not undergone&#xD;
             hysterectomy, including history of menorrhagia, metrorrhagia or polymenorrhea&#xD;
&#xD;
          9. Pregnant or breast-feeding&#xD;
&#xD;
         10. Males with a history of hormone therapy within 3 months prior to screening&#xD;
&#xD;
         11. Administration of any blood product or anticoagulant within 3 months prior to study&#xD;
             entry or any non-steroidal anti-inflammatory drug or cyclooxygenase inhibitor within 2&#xD;
             weeks prior to dosing.&#xD;
&#xD;
         12. Taking any type of medication for more than 14 consecutive days within the 4 weeks&#xD;
             prior to study entry&#xD;
&#xD;
         13. Positive serologic test for HIV, hepatitis C antibody, or hepatitis B surface antigen&#xD;
&#xD;
         14. Donation of blood or blood products within 56 days prior to screening&#xD;
&#xD;
         15. History of randomization in any prior study of PER977&#xD;
&#xD;
         16. Randomization in any study with an investigational compound or device within 30 days&#xD;
             prior to signing informed consent&#xD;
&#xD;
         17. Active drug or alcohol dependence within the prior 12 months or any condition that, in&#xD;
             the opinion of the Investigator, would interfere with adherence to study protocol&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Scott Rasmussen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Quintiles, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Quintiles</name>
      <address>
        <city>Overland Park</city>
        <state>Kansas</state>
        <zip>66211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2017</verification_date>
  <study_first_submitted>June 2, 2014</study_first_submitted>
  <study_first_submitted_qc>July 30, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 1, 2014</study_first_posted>
  <disposition_first_submitted>September 18, 2017</disposition_first_submitted>
  <disposition_first_submitted_qc>September 18, 2017</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">September 26, 2017</disposition_first_posted>
  <last_update_submitted>May 19, 2020</last_update_submitted>
  <last_update_submitted_qc>May 19, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 21, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PER977</keyword>
  <keyword>enoxaparin</keyword>
  <keyword>anticoagulation reversal</keyword>
  <keyword>whole blood clotting time</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Enoxaparin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT02206100
org study id: PER977-01-003
nct id: NCT02206100
lead sponsor: 
has dmc: No
PER977 administration following a single dose of enoxaparin
Single escalating doses of PER977 from 100 to 300 mg, of 25 mg PER977 x 4 doses will be
      administered following administration of enoxaparin. Serial pharmacokinetic and
      pharmacodynamic assessments ( whole blood clotting time) will be performed. Adverse events
      will be monitored.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Other
masking: Single (Participant)
measure: Number of adverse events
time frame: 1 day
description: Assessment of the number of subjects who experience adverse events and the number and type of adverse events
measure: Reversal of enoxaparin anticoagulation
time frame: 1 day
description: Measurement of the degree of change in whole blood clotting time and the proportion of subjects who achieve complete or partial reversal of anticoagulation
measure: Pharmacokinetics of enoxaparin
time frame: 1 day
description: Measurement of the pharmacokinetic characteristics of enoxaparin
measure: Pharmacokinetics of PER977 and its metabolite
time frame: 2 days
description: Measurement of the pharmacokinetic characteristics of PER977 and its metabolite
arm group label: Cohort 1
arm group type: Experimental
description: 100 mg PER977 (10 subjects); the dose may be repeated two (2) times after an approximate one (1) hour interval for a maximum total of three (3) doses
arm group label: Cohort 2
arm group type: Experimental
description: 200 mg PER977 (10 subjects); the dose may be repeated once at approximately one hour for a maximum total of two (2) doses
arm group label: Cohort 3
arm group type: Experimental
description: 300 mg PER977 (10 subjects); the dose may be repeated once at approximately one hour after the initial dose for a maximum of total of two (2) doses
arm group label: Cohort 4
arm group type: Experimental
description: 4 x 25 mg PER977 (10 subjects); study drug will be administered every 30 minutes for a total of 4 doses (cumulative dose of 100 mg PER977)
intervention type: Drug
intervention name: PER977
description: reversal of edoxaban-induced anticoagulation
arm group label: Cohort 1
arm group label: Cohort 2
arm group label: Cohort 3
arm group label: Cohort 4
intervention type: Drug
intervention name: Placebo
description: Reversal of edoxaban-induced anticoagulation
arm group label: Cohort 1
arm group label: Cohort 2
arm group label: Cohort 3
arm group label: Cohort 4
intervention type: Drug
intervention name: enoxaparin
arm group label: Cohort 1
arm group label: Cohort 2
arm group label: Cohort 3
arm group label: Cohort 4
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Scott Rasmussen, MD
role: Principal Investigator
affiliation: Quintiles, Inc.
facility: 
country: United States
responsible party type: Sponsor
mesh term: Enoxaparin