<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/NCT02217917</url>
  </required_header>
  <id_info>
    <org_study_id>B5201007</org_study_id>
    <secondary_id>2014-002748-41</secondary_id>
    <nct_id>NCT02217917</nct_id>
  </id_info>
  <brief_title>Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Subcutaneous Rivipansel With rHuPH20 in Healthy Subjects</brief_title>
  <official_title>A Phase 1, Randomized, Double Blind, Sponsor Open, Placebo Controlled, Single And Multiple Ascending Dose Study To Evaluate The Safety, Tolerability, And Pharmacokinetics Of Rivipansel (pf 06460031) Following Subcutaneous Administration With Rhuph20 (pf 06744547) In Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GlycoMimetics Incorporated</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>GlycoMimetics Incorporated</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a 2 part study designed to provide an initial assessment on the safety, tolerability,&#xD;
      and PK of rivipansel, following single ascending (Part 1) and multiple ascending dosing (Part&#xD;
      2) given subcutaneously with rHuPH20, in healthy subjects. Part 1 of the study will be&#xD;
      conducted using a cross-over design while Part 2 of the study will be conducted using a&#xD;
      parallel design.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2015</start_date>
  <completion_date type="Actual">April 2016</completion_date>
  <primary_completion_date type="Actual">April 2016</primary_completion_date>
  <phase>Phase 1</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>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Assessment of adverse events (AEs)</measure>
    <time_frame>Baseline up to 7 days of dosing</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessment of cardiac conduction intervals as assessed via 12-lead electrocardiogram (ECG)</measure>
    <time_frame>Baseline up to 7 days of dosing</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessment of vital signs (including blood pressure and pulse rate)</measure>
    <time_frame>Baseline up to 7 days of dosing</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessment of clinical laboratory tests</measure>
    <time_frame>Baseline up to 7 days of dosing</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax) for rivipansel following single dose</measure>
    <time_frame>Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach Maximum Observed Plasma Concentration (Tmax) for rivipansel following single dose</measure>
    <time_frame>Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for rivipansel following single dose</measure>
    <time_frame>Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for rivipansel following single dose</measure>
    <time_frame>Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose-Normalized Cmax for rivipansel following single dose</measure>
    <time_frame>Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose-Normalized AUClast for rivipansel</measure>
    <time_frame>Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose-Normalized AUCinf for rivipansel</measure>
    <time_frame>Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Decay Half-Life (t1/2) for rivipansel following single dose</measure>
    <time_frame>Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Clearance (CL/F) for rivipansel following single dose</measure>
    <time_frame>Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Volume of Distribution (Vz/F) for rivipansel following single dose</measure>
    <time_frame>Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax) for rivipansel following multiple dose</measure>
    <time_frame>Days 1, 7</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach Maximum Observed Plasma Concentration (Tmax) for rivipansel following multiple dose</measure>
    <time_frame>Days 1, 7</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Curve from Time Zero to end of dosing interval (AUCtau) for rivipansel following multiple dose administration, where tau is 12 hours</measure>
    <time_frame>Days 1, 7</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose-Normalized Cmax for rivipansel following multiple dose administration</measure>
    <time_frame>Days 1, 7</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose-Normalized AUCtau for rivipansel following multiple dose administration</measure>
    <time_frame>Days 1, 7</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Decay Half-Life (t1/2) for rivipansel following multiple dose</measure>
    <time_frame>Day 7</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimum Observed Plasma Concentration (Cmin) for rivipansel following multiple dose</measure>
    <time_frame>Day 7</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Clearance (CL/F) for rivipansel following multiple dose</measure>
    <time_frame>Day 7</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak to Trough Ratio (PTR) of plasma concentration for rivipanselmultiple dose administration</measure>
    <time_frame>Day 7</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation ratio for Area Under the Curve during the dosing interval (Rac) for rivipansel</measure>
    <time_frame>Day 7</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">27</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single ascending dose in 3 period cross-over design (with optional 4th period)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Multiple ascending dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Multiple ascending dose</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rivipansel</intervention_name>
    <description>Rivipansel administered as a single dose subcutaneously with rHuPH20 in cross-over fashion. Each subject may receive up to 4 study treatments (placebo and up to 3 doses of rivipansel). The planned dose levels are 350 mg, 1210 mg, and 4200 mg (these are subject to change based on emerging data).</description>
    <arm_group_label>Cohort 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Matched Placebo administered as single dose subcutaneously with rHuPH20.</description>
    <arm_group_label>Cohort 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rivipansel</intervention_name>
    <description>Rivipansel administered q12h for 7 days (a total of 13 doses) subcutaneously with rHuPH20. Planned doses are 1400 mg loading and 700 mg maintenance for 12 doses (these are subject to change based on emerging data).</description>
    <arm_group_label>Cohort 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rivipansel</intervention_name>
    <description>Rivipansel administered q12h for 7 days (a total of 13 doses) subcutaneously with rHuPH20. Planned doses are 2800 mg loading and 1400 mg maintenance for 12 doses (these are subject to change based on emerging data).</description>
    <arm_group_label>Cohort 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Matched Placebo administered q12h for 7 days (a total of 13 doses) subcutaneously with rHuPH20.</description>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_label>Cohort 3</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male and/or female subjects of non-childbearing potential between the ages of&#xD;
             18 and 55 years, inclusive.&#xD;
&#xD;
          -  Body Mass Index 17.5 - 30.5 kg/m2 and body weight &gt;50 kg at Screening.&#xD;
&#xD;
          -  Normal skin without potentially obscuring features in the area intended for infusion.&#xD;
&#xD;
          -  Subjects willing to defer receiving prophylactic immunizations (eg, influenza or&#xD;
             pneumococcal vaccines) during the study.&#xD;
&#xD;
          -  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 pertinent&#xD;
             aspects of the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Evidence or history of clinically significant hematological, renal, endocrine,&#xD;
             pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or&#xD;
             allergic disease (including drug allergies, but excluding untreated, asymptomatic,&#xD;
             seasonal allergies at time of dosing).&#xD;
&#xD;
          -  History of a recent major surgery (within 3 months of screening).&#xD;
&#xD;
          -  Serious infection within 1 month of screening.&#xD;
&#xD;
          -  Subjects with chronic skin condition that may interfere in the assessment of emergent&#xD;
             safety data.&#xD;
&#xD;
          -  A positive urine drug screen.&#xD;
&#xD;
          -  Known sensitivity to hyaluronidases.&#xD;
&#xD;
          -  History of hepatitis or positive testing for human immunodeficiency virus (HIV),&#xD;
             hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or hepatitis C&#xD;
             antibodies (HCV).&#xD;
&#xD;
          -  Unwilling or unable to comply with the Lifestyle Guidelines described in this&#xD;
             protocol.&#xD;
&#xD;
          -  Subjects who are investigational site staff members directly involved in the conduct&#xD;
             of the study and their family members, site staff members otherwise supervised by the&#xD;
             Investigator, or subjects who are Pfizer employees directly involved in the conduct of&#xD;
             the study.&#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>Pfizer CT.gov Call Center</last_name>
    <role>Study Director</role>
    <affiliation>Pfizer</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Pfizer Clinical Research Unit</name>
      <address>
        <city>Brussels</city>
        <zip>B-1070</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>August 13, 2014</study_first_submitted>
  <study_first_submitted_qc>August 13, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 15, 2014</study_first_posted>
  <last_update_submitted>June 16, 2020</last_update_submitted>
  <last_update_submitted_qc>June 16, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 18, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Healthy subjects</keyword>
  <keyword>Randomized</keyword>
  <keyword>Double-blind</keyword>
  <keyword>Single ascending dose</keyword>
  <keyword>Multiple ascending dose</keyword>
  <!-- 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/NCT02217917
org study id: B5201007
secondary id: 2014-002748-41
nct id: NCT02217917
lead sponsor: 
has dmc: No
This is a 2 part study designed to provide an initial assessment on the safety, tolerability,
      and PK of rivipansel, following single ascending (Part 1) and multiple ascending dosing (Part
      2) given subcutaneously with rHuPH20, in healthy subjects. Part 1 of the study will be
      conducted using a cross-over design while Part 2 of the study will be conducted using a
      parallel design.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Assessment of adverse events (AEs)
time frame: Baseline up to 7 days of dosing
measure: Assessment of cardiac conduction intervals as assessed via 12-lead electrocardiogram (ECG)
time frame: Baseline up to 7 days of dosing
measure: Assessment of vital signs (including blood pressure and pulse rate)
time frame: Baseline up to 7 days of dosing
measure: Assessment of clinical laboratory tests
time frame: Baseline up to 7 days of dosing
measure: Maximum Observed Plasma Concentration (Cmax) for rivipansel following single dose
time frame: Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) for rivipansel following single dose
time frame: Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for rivipansel following single dose
time frame: Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for rivipansel following single dose
time frame: Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
measure: Dose-Normalized Cmax for rivipansel following single dose
time frame: Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
measure: Dose-Normalized AUClast for rivipansel
time frame: Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
measure: Dose-Normalized AUCinf for rivipansel
time frame: Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
measure: Plasma Decay Half-Life (t1/2) for rivipansel following single dose
time frame: Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
measure: Apparent Clearance (CL/F) for rivipansel following single dose
time frame: Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
measure: Apparent Volume of Distribution (Vz/F) for rivipansel following single dose
time frame: Samples are collected pre-dose and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 H following single dose administration
measure: Maximum Observed Plasma Concentration (Cmax) for rivipansel following multiple dose
time frame: Days 1, 7
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) for rivipansel following multiple dose
time frame: Days 1, 7
measure: Area Under the Curve from Time Zero to end of dosing interval (AUCtau) for rivipansel following multiple dose administration, where tau is 12 hours
time frame: Days 1, 7
measure: Dose-Normalized Cmax for rivipansel following multiple dose administration
time frame: Days 1, 7
measure: Dose-Normalized AUCtau for rivipansel following multiple dose administration
time frame: Days 1, 7
measure: Plasma Decay Half-Life (t1/2) for rivipansel following multiple dose
time frame: Day 7
measure: Minimum Observed Plasma Concentration (Cmin) for rivipansel following multiple dose
time frame: Day 7
measure: Apparent Clearance (CL/F) for rivipansel following multiple dose
time frame: Day 7
measure: Peak to Trough Ratio (PTR) of plasma concentration for rivipanselmultiple dose administration
time frame: Day 7
measure: Accumulation ratio for Area Under the Curve during the dosing interval (Rac) for rivipansel
time frame: Day 7
arm group label: Cohort 1
arm group type: Experimental
description: Single ascending dose in 3 period cross-over design (with optional 4th period)
arm group label: Cohort 2
arm group type: Experimental
description: Multiple ascending dose
arm group label: Cohort 3
arm group type: Experimental
description: Multiple ascending dose
intervention type: Drug
intervention name: Rivipansel
description: Rivipansel administered as a single dose subcutaneously with rHuPH20 in cross-over fashion. Each subject may receive up to 4 study treatments (placebo and up to 3 doses of rivipansel). The planned dose levels are 350 mg, 1210 mg, and 4200 mg (these are subject to change based on emerging data).
arm group label: Cohort 1
intervention type: Drug
intervention name: Placebo
description: Matched Placebo administered as single dose subcutaneously with rHuPH20.
arm group label: Cohort 1
intervention type: Drug
intervention name: Rivipansel
description: Rivipansel administered q12h for 7 days (a total of 13 doses) subcutaneously with rHuPH20. Planned doses are 1400 mg loading and 700 mg maintenance for 12 doses (these are subject to change based on emerging data).
arm group label: Cohort 2
intervention type: Drug
intervention name: Rivipansel
description: Rivipansel administered q12h for 7 days (a total of 13 doses) subcutaneously with rHuPH20. Planned doses are 2800 mg loading and 1400 mg maintenance for 12 doses (these are subject to change based on emerging data).
arm group label: Cohort 3
intervention type: Drug
intervention name: Placebo
description: Matched Placebo administered q12h for 7 days (a total of 13 doses) subcutaneously with rHuPH20.
arm group label: Cohort 2
arm group label: Cohort 3
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Pfizer CT.gov Call Center
role: Study Director
affiliation: Pfizer
facility: 
country: Belgium
responsible party type: Sponsor