<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/NCT01720537</url>
  </required_header>
  <id_info>
    <org_study_id>B3091001</org_study_id>
    <nct_id>NCT01720537</nct_id>
  </id_info>
  <brief_title>A Study To Assess The Safety Of PF-05335810 In Hypercholesterolemic Subjects</brief_title>
  <official_title>A Phase I, Placebo-Controlled, Randomized Study To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Following Single, Ascending Doses Of PF-05335810 In Hypercholesterolemic Subjects, With One, Open-Label, Multiple Fixed Dosage Cohort</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pfizer</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is to evaluate the safety, tolerability and immunogenicity of single, ascending or&#xD;
      multiple fixed subcutaneous and intravenous administrations of PF 05335810 to&#xD;
      hypercholesterolemic subjects when added on to a daily statin dose.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>July 2012</start_date>
  <completion_date type="Actual">October 2013</completion_date>
  <primary_completion_date type="Actual">October 2013</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>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)</measure>
    <time_frame>Baseline up to Day 85/169 or Early Termination (ET)</time_frame>
    <description>Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Relatedness to [study drug] was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Laboratory Test Values of Potential Clinical Importance</measure>
    <time_frame>Baseline up to Day 85/169 or Early Termination (ET)</time_frame>
    <description>Pre-defined criteria were established for each laboratory test to define the values that would be identified as of potential clinical importance.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Heart Rate</measure>
    <time_frame>Baseline, Day 1 to 85/169 or ET</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Diastolic Blood Pressure</measure>
    <time_frame>Baseline, Day 1 to 85/169 or ET</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Electrocardiogram (ECG) Parameters</measure>
    <time_frame>Baseline, Day 1 to 85/169 or ET</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Laboratory Test Values of Potential Clinical Importance</measure>
    <time_frame>Baseline, Day 1 to 85/169 or ET</time_frame>
    <description>Pre-defined criteria were established for each laboratory test to define the values that would be identified as of potential clinical importance.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)]</measure>
    <time_frame>Day1 pre-dose to Day 85/169 or ET</time_frame>
    <description>AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]</measure>
    <time_frame>Day1 pre-dose to Day 85/169 or ET</time_frame>
    <description>AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax)</measure>
    <time_frame>Day1 pre-dose to Day 85/169 or ET</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach Maximum Observed Plasma Concentration (Tmax)</measure>
    <time_frame>Day1 pre-dose to Day 85/169 or ET</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Volume of Distribution (Vz/F)</measure>
    <time_frame>Day1 pre-dose to Day 85/169 or ET</time_frame>
    <description>Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Oral Clearance (CL/F)</measure>
    <time_frame>Day1 pre-dose to Day 85/169 or ET</time_frame>
    <description>Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Decay Half-Life (t1/2)</measure>
    <time_frame>Day1 pre-dose to Day 85/169 or ET</time_frame>
    <description>Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute Bioavailability (%F)</measure>
    <time_frame>Day1 pre-dose to Day 85/169 or ET</time_frame>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">133</enrollment>
  <condition>Hypercholesterolemia</condition>
  <arm_group>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 6</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>PF-05335810 Dose A</intervention_name>
    <description>Single SC Injection</description>
    <arm_group_label>Cohort 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>PF-05335810 Dose B</intervention_name>
    <description>Single Subcutaneous Injection(s)</description>
    <arm_group_label>Cohort 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Single Subcutaneous Injection(s)</description>
    <arm_group_label>Cohort 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>PF-05335810 Dose B</intervention_name>
    <description>Single Intravenous Infusion</description>
    <arm_group_label>Cohort 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Single Intravenous Infusion</description>
    <arm_group_label>Cohort 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>PF-04950615 Dose A</intervention_name>
    <description>Single Subcutaneous Injection(s)</description>
    <arm_group_label>Cohort 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>PF-04950615 Dose A</intervention_name>
    <description>Single Intravenous Infusion</description>
    <arm_group_label>Cohort 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>PF-05335810 Dose C</intervention_name>
    <description>Single Subcutaneous Injection(s)</description>
    <arm_group_label>Cohort 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Single Subcutaneous Injection(s)</description>
    <arm_group_label>Cohort 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>PF-05335810 Dose C</intervention_name>
    <description>Single Intravenous Infusion</description>
    <arm_group_label>Cohort 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Single Intravenous Infusion</description>
    <arm_group_label>Cohort 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>PF-04950615</intervention_name>
    <description>Single Subcutaneous Injection(s)</description>
    <arm_group_label>Cohort 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>PF-05335810 Dose D</intervention_name>
    <description>Single Subcutaneous Injection(s)</description>
    <arm_group_label>Cohort 4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Single Subcutaneous Injection(s)</description>
    <arm_group_label>Cohort 4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>PF-05335810 Dose E</intervention_name>
    <description>Multiple fixed dosages administered in subcutaneous injections, monthly for 3 months.</description>
    <arm_group_label>Cohort 5</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>PF-05335810 Dose D</intervention_name>
    <description>Single Intravenous Infusion</description>
    <arm_group_label>Cohort 6</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Single Intravenous Infusion</description>
    <arm_group_label>Cohort 6</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  On stable daily doses of a statin for 45 days prior to receiving study treatment.&#xD;
&#xD;
          -  Fasting LDL C equal or greater than 80 mg/dL at screening and visit approximately 1&#xD;
             week prior to randomization.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of a cardiovascular or cerebrovascular event or procedure within one year of&#xD;
             randomization.&#xD;
&#xD;
          -  Poorly controlled type 1 or type 2 diabetes mellitus (defined as HbA1c &gt;9%).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</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 Investigational Site</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06511</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pfizer Investigational Site</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33169</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pfizer Investigational Site</name>
      <address>
        <city>South Miami</city>
        <state>Florida</state>
        <zip>33143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pfizer Investigational Site</name>
      <address>
        <city>Overland Park</city>
        <state>Kansas</state>
        <zip>66212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pfizer Investigational Site</name>
      <address>
        <city>Kalamazoo</city>
        <state>Michigan</state>
        <zip>49007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pfizer Investigational Site</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45227</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pfizer Investigational Site</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B3091001&amp;StudyName=A%20Study%20To%20Assess%20The%20Safety%20Of%20PF-05335810%20In%20Hypercholesterolemic%20Subjects</url>
    <description>To obtain contact information for a study center near you, click here.</description>
  </link>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>August 3, 2012</study_first_submitted>
  <study_first_submitted_qc>October 31, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 2, 2012</study_first_posted>
  <last_update_submitted>November 30, 2018</last_update_submitted>
  <last_update_submitted_qc>November 30, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 4, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>High Cholesterol</keyword>
  <keyword>Dyslipidemia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypercholesterolemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bococizumab</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01720537
org study id: B3091001
nct id: NCT01720537
lead sponsor: 
has dmc: No
This study is to evaluate the safety, tolerability and immunogenicity of single, ascending or
      multiple fixed subcutaneous and intravenous administrations of PF 05335810 to
      hypercholesterolemic subjects when added on to a daily statin dose.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
time frame: Baseline up to Day 85/169 or Early Termination (ET)
description: Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Relatedness to [study drug] was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category.
measure: Number of Participants With Laboratory Test Values of Potential Clinical Importance
time frame: Baseline up to Day 85/169 or Early Termination (ET)
description: Pre-defined criteria were established for each laboratory test to define the values that would be identified as of potential clinical importance.
measure: Change From Baseline in Heart Rate
time frame: Baseline, Day 1 to 85/169 or ET
measure: Diastolic Blood Pressure
time frame: Baseline, Day 1 to 85/169 or ET
measure: Change From Baseline in Electrocardiogram (ECG) Parameters
time frame: Baseline, Day 1 to 85/169 or ET
measure: Number of Participants With Laboratory Test Values of Potential Clinical Importance
time frame: Baseline, Day 1 to 85/169 or ET
description: Pre-defined criteria were established for each laboratory test to define the values that would be identified as of potential clinical importance.
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)]
time frame: Day1 pre-dose to Day 85/169 or ET
description: AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8).
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]
time frame: Day1 pre-dose to Day 85/169 or ET
description: AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t)
measure: Maximum Observed Plasma Concentration (Cmax)
time frame: Day1 pre-dose to Day 85/169 or ET
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
time frame: Day1 pre-dose to Day 85/169 or ET
measure: Apparent Volume of Distribution (Vz/F)
time frame: Day1 pre-dose to Day 85/169 or ET
description: Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
measure: Apparent Oral Clearance (CL/F)
time frame: Day1 pre-dose to Day 85/169 or ET
description: Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
measure: Plasma Decay Half-Life (t1/2)
time frame: Day1 pre-dose to Day 85/169 or ET
description: Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
measure: Absolute Bioavailability (%F)
time frame: Day1 pre-dose to Day 85/169 or ET
arm group label: Cohort 1
arm group type: Experimental
arm group label: Cohort 2
arm group type: Experimental
arm group label: Cohort 3
arm group type: Experimental
arm group label: Cohort 4
arm group type: Experimental
arm group label: Cohort 5
arm group type: Experimental
arm group label: Cohort 6
arm group type: Experimental
intervention type: Biological
intervention name: PF-05335810 Dose A
description: Single SC Injection
arm group label: Cohort 1
intervention type: Biological
intervention name: PF-05335810 Dose B
description: Single Subcutaneous Injection(s)
arm group label: Cohort 2
intervention type: Biological
intervention name: Placebo
description: Single Subcutaneous Injection(s)
arm group label: Cohort 2
intervention type: Biological
intervention name: PF-05335810 Dose B
description: Single Intravenous Infusion
arm group label: Cohort 2
intervention type: Biological
intervention name: Placebo
description: Single Intravenous Infusion
arm group label: Cohort 2
intervention type: Biological
intervention name: PF-04950615 Dose A
description: Single Subcutaneous Injection(s)
arm group label: Cohort 2
intervention type: Biological
intervention name: PF-04950615 Dose A
description: Single Intravenous Infusion
arm group label: Cohort 2
intervention type: Biological
intervention name: PF-05335810 Dose C
description: Single Subcutaneous Injection(s)
arm group label: Cohort 3
intervention type: Biological
intervention name: Placebo
description: Single Subcutaneous Injection(s)
arm group label: Cohort 3
intervention type: Biological
intervention name: PF-05335810 Dose C
description: Single Intravenous Infusion
arm group label: Cohort 3
intervention type: Biological
intervention name: Placebo
description: Single Intravenous Infusion
arm group label: Cohort 3
intervention type: Biological
intervention name: PF-04950615
description: Single Subcutaneous Injection(s)
arm group label: Cohort 3
intervention type: Biological
intervention name: PF-05335810 Dose D
description: Single Subcutaneous Injection(s)
arm group label: Cohort 4
intervention type: Biological
intervention name: Placebo
description: Single Subcutaneous Injection(s)
arm group label: Cohort 4
intervention type: Biological
intervention name: PF-05335810 Dose E
description: Multiple fixed dosages administered in subcutaneous injections, monthly for 3 months.
arm group label: Cohort 5
intervention type: Biological
intervention name: PF-05335810 Dose D
description: Single Intravenous Infusion
arm group label: Cohort 6
intervention type: Biological
intervention name: Placebo
description: Single Intravenous Infusion
arm group label: Cohort 6
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Pfizer CT.gov Call Center
role: Study Director
affiliation: Pfizer
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B3091001&StudyName=A%20Study%20To%20Assess%20The%20Safety%20Of%20PF-05335810%20In%20Hypercholesterolemic%20Subjects
description: To obtain contact information for a study center near you, click here.
responsible party type: Sponsor
mesh term: Hypercholesterolemia
mesh term: Bococizumab
mesh term: Antibodies, Monoclonal