<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/NCT02216097</url>
  </required_header>
  <id_info>
    <org_study_id>B0541013</org_study_id>
    <nct_id>NCT02216097</nct_id>
  </id_info>
  <brief_title>A Study To Assess the Effects Of PF-04457845 On BOLD fMRI In Subjects With Post Traumatic Stress Disorder</brief_title>
  <official_title>A Randomized, Double Blind, Placebo Controlled, Parallel Group Phase 2 Study To Assess Effects Of Pf 04457845 On Bold Functional Mri In Subjects With Ptsd</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>
      The purpose of the study is to evaluate proof of mechanism of PF-04457845, using a&#xD;
      well-established neuroimaging paradigm including behavioral tasks selected to activate&#xD;
      neuro-circuitry relevant to Post Traumatic Stress Disorder. It is hypothesized that&#xD;
      PF-04457845 will modulate the Blood-oxygen-level dependent Functional Magnetic Resonance&#xD;
      Imaging signal from the relevant neuro-circuits in patients with Post Traumatic Stress&#xD;
      Disorder.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase II, randomized, placebo-controlled, parallel group design study in male and&#xD;
      female subjects with moderate-to-severe Post Traumatic Stress Disorder between the ages of 18&#xD;
      and 60 years old. During this study, a dose of 4 mg PF-04457845 will be administered in the&#xD;
      morning on Days 1-7. On Each subject will undergo a resting state fMRI (pre and post and day&#xD;
      8), a fearful vs. neutral faces fMRI task and a fear extinction fMRI paradigm. The Emotional&#xD;
      Faces Paradigm and resting state tasks will be performed on Day 1 (prior to drug or placebo)&#xD;
      and on Day 8. Acquisition of fear conditioning will be performed during the first imaging&#xD;
      session on Day 1. After the first imaging session on Day 1, subjects will complete behavioral&#xD;
      rating scales and then be dosed. Approximately six hours after dosing subjects will re-enter&#xD;
      the scanner and perform the fear extinction paradigm. On Day 2, subjects will perform the&#xD;
      fear extinction memory retention task within the scanner. Further physiological monitoring,&#xD;
      including skin conductance and heart rate, will take place during the fear extinction&#xD;
      paradigm. One safety follow-up visit will occur between Days 11-18.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The study stopped based on Pfizer portfolio prioritization and not due to safety and/or&#xD;
    efficacy concern or change in benefit:risk assessment of PF-04457845.&#xD;
  </why_stopped>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">March 2015</completion_date>
  <primary_completion_date type="Actual">March 2015</primary_completion_date>
  <phase>Phase 2</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>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline Blood-Oxygen-Level Dependent (BOLD) Functional Magnetic Resonance Imaging fMRI) Percent Signal Change in Fearful Versus Neutral Face Contrast in Bilateral Amygdala</measure>
    <time_frame>Baseline, Day 8</time_frame>
    <description>Baseline BOLD fMRI percent signal change measured from baseline in fearful versus neutral face contrast during the emotional face processing task in bilateral amygdala.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in BOLD fMRI Percent Activation in Bilateral Ventromedial Pre-Frontal Cortex (vmPFC)</measure>
    <time_frame>Baseline, Day 2</time_frame>
    <description>Difference measured in BOLD fMRI percent activation in the bilateral vmPFC during the fear extinction recall phase of the fear extinction paradigm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in BOLD fMRI Percent Signal Change in Fearful Versus Neutral Face Contrast in Right Amygdala</measure>
    <time_frame>Baseline, Day 8</time_frame>
    <description>Difference measured in BOLD fMRI percent signal change in the right amygdala in fear versus neutral faces during the emotional face processing task.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in BOLD fMRI Percent Signal Change in Fearful Versus Neutral Face Contrast in Left Amygdala</measure>
    <time_frame>Baseline, Day 8</time_frame>
    <description>Difference measured in BOLD fMRI percent signal change in the left amygdala in fearful versus neutral faces during face processing task.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Abnormal Physical Examination Findings</measure>
    <time_frame>Baseline to up to Day 18</time_frame>
    <description>The full physical examination included head, ears, eyes, nose, mouth, skin, heart, and lung examinations, lymph nodes, gastrointestinal, skeletal, and neurological systems.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Withdrawals Due to AEs</measure>
    <time_frame>Baseline up to 28 days after last study drug administration (Day 35)</time_frame>
    <description>An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last study drug administration that were absent before treatment or that worsened relative to pretreatment state. AEs included non-serious AEs and SAEs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Clinical Laboratory Values Meeting Criteria for Potential Clinical Concern</measure>
    <time_frame>Baseline up to Day 18</time_frame>
    <description>The following laboratory parameters were analyzed: hematology (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes; liver function (aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium, bicarbonate); chemistry (glucose); urinalysis (dipstick) (urine pH, urine glucose, urine protein, urine blood, urine ketones, urine bilirubin, urine nitrite, urine leukocyte esterase); urinalysis microscopy (urine red blood cell, urine white blood cell, urine bacteria). Only parameters with abnormal values were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern</measure>
    <time_frame>Baseline up to Day 18</time_frame>
    <description>Vital signs assessment included pulse rate and blood pressure. Criteria for vital sign values meeting potential clinical concern included: supine pulse rate &lt;40 or &gt;120 beats per minute (bpm), standing pulse rate &lt;40 or &gt;140 bpm; systolic blood pressure (SBP) of &gt;=30 millimeters of mercury (mmHg) change from baseline or SBP &lt;90 mmHg; diastolic blood pressure (DBP) &gt;=20 mmHg change from baseline or DBP &lt;50 mmHg.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Post-Baseline Electrocardiogram (ECG) Values Meeting Criteria of Potential Clinical Concern</measure>
    <time_frame>Baseline up to Day 18</time_frame>
    <description>ECG criteria of potential clinical concern were QTc absolute value &gt;=450 milliseconds (msec) or QTc absolute change &gt;=30 msec.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Post-Traumatic Stress Disorder</condition>
  <arm_group>
    <arm_group_label>Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PF-04457845</intervention_name>
    <description>4mg PF-04457845 tablet taken once daily for 7 days.</description>
    <arm_group_label>Treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Matching placebo tablet taken once daily for 7 days.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men and women 18-60 years of age with a primary psychiatric diagnosis of Post&#xD;
             Traumatic Stress Disorder&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Other psychiatric illness requiring current treatment with medication.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 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>Clinical and Translational Science Institute (CTSI)</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NYU CTSI Research Pharmacy (Drug Shipment Address)</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NYU School of Medicine</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</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=B0541013&amp;StudyName=A%20Study%20To%20Assess%20Effects%20Of%20PF-04457845%20On%20Blood-Oxygen-Level%20Dependent%20Functional%20Magnetic%20Resonance%20Imaging%20In%20Subjects%20With%20Post%20Traum</url>
    <description>To obtain contact information for a study center near you, click here.</description>
  </link>
  <verification_date>May 2016</verification_date>
  <study_first_submitted>August 12, 2014</study_first_submitted>
  <study_first_submitted_qc>August 12, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2014</study_first_posted>
  <results_first_submitted>March 10, 2016</results_first_submitted>
  <results_first_submitted_qc>March 10, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">April 8, 2016</results_first_posted>
  <last_update_submitted>May 26, 2016</last_update_submitted>
  <last_update_submitted_qc>May 26, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">June 29, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stress Disorders, Traumatic</mesh_term>
    <mesh_term>Stress Disorders, Post-Traumatic</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>PF-04457845</title>
          <description>PF-04457845 4 milligrams (mg) was orally administered once daily in the morning on Days 1 to 7.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo matched to PF-04457845 was orally administered once daily in the morning on Days 1 to 7.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="6"/>
              </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>PF-04457845</title>
          <description>PF-04457845 4 milligrams (mg) was orally administered once daily in the morning on Days 1 to 7.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo matched to PF-04457845 was orally administered once daily in the morning on Days 1 to 7.</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="8"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="14"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="35.6" spread="11.4"/>
                    <measurement group_id="B2" value="36.2" spread="15.1"/>
                    <measurement group_id="B3" value="35.9" spread="12.6"/>
                  </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="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline Blood-Oxygen-Level Dependent (BOLD) Functional Magnetic Resonance Imaging fMRI) Percent Signal Change in Fearful Versus Neutral Face Contrast in Bilateral Amygdala</title>
        <description>Baseline BOLD fMRI percent signal change measured from baseline in fearful versus neutral face contrast during the emotional face processing task in bilateral amygdala.</description>
        <time_frame>Baseline, Day 8</time_frame>
        <population>There were no efficacy evaluations done in this study because of a change in the planned analysis after the study was prematurely terminated due to Good Clinical Practice (GCP) non-compliance that resulted in data integrity and quality issues.</population>
        <group_list>
          <group group_id="O1">
            <title>PF-04457845</title>
            <description>PF-04457845 4 milligrams (mg) was orally administered once daily in the morning on Days 1 to 7.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to PF-04457845 was orally administered once daily in the morning on Days 1 to 7.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline Blood-Oxygen-Level Dependent (BOLD) Functional Magnetic Resonance Imaging fMRI) Percent Signal Change in Fearful Versus Neutral Face Contrast in Bilateral Amygdala</title>
          <description>Baseline BOLD fMRI percent signal change measured from baseline in fearful versus neutral face contrast during the emotional face processing task in bilateral amygdala.</description>
          <population>There were no efficacy evaluations done in this study because of a change in the planned analysis after the study was prematurely terminated due to Good Clinical Practice (GCP) non-compliance that resulted in data integrity and quality issues.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in BOLD fMRI Percent Activation in Bilateral Ventromedial Pre-Frontal Cortex (vmPFC)</title>
        <description>Difference measured in BOLD fMRI percent activation in the bilateral vmPFC during the fear extinction recall phase of the fear extinction paradigm.</description>
        <time_frame>Baseline, Day 2</time_frame>
        <population>There were no efficacy evaluations done in this study because of a change in the planned analysis after the study was prematurely terminated due to GCP non-compliance that resulted in data integrity and quality issues.</population>
        <group_list>
          <group group_id="O1">
            <title>PF-04457845</title>
            <description>PF-04457845 4 milligrams (mg) was orally administered once daily in the morning on Days 1 to 7.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to PF-04457845 was orally administered once daily in the morning on Days 1 to 7.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in BOLD fMRI Percent Activation in Bilateral Ventromedial Pre-Frontal Cortex (vmPFC)</title>
          <description>Difference measured in BOLD fMRI percent activation in the bilateral vmPFC during the fear extinction recall phase of the fear extinction paradigm.</description>
          <population>There were no efficacy evaluations done in this study because of a change in the planned analysis after the study was prematurely terminated due to GCP non-compliance that resulted in data integrity and quality issues.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in BOLD fMRI Percent Signal Change in Fearful Versus Neutral Face Contrast in Right Amygdala</title>
        <description>Difference measured in BOLD fMRI percent signal change in the right amygdala in fear versus neutral faces during the emotional face processing task.</description>
        <time_frame>Baseline, Day 8</time_frame>
        <population>There were no efficacy evaluations done in this study because of a change in the planned analysis after the study was prematurely terminated due to GCP non-compliance that resulted in data integrity and quality issues.</population>
        <group_list>
          <group group_id="O1">
            <title>PF-04457845</title>
            <description>PF-04457845 4 milligrams (mg) was orally administered once daily in the morning on Days 1 to 7.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to PF-04457845 was orally administered once daily in the morning on Days 1 to 7.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in BOLD fMRI Percent Signal Change in Fearful Versus Neutral Face Contrast in Right Amygdala</title>
          <description>Difference measured in BOLD fMRI percent signal change in the right amygdala in fear versus neutral faces during the emotional face processing task.</description>
          <population>There were no efficacy evaluations done in this study because of a change in the planned analysis after the study was prematurely terminated due to GCP non-compliance that resulted in data integrity and quality issues.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in BOLD fMRI Percent Signal Change in Fearful Versus Neutral Face Contrast in Left Amygdala</title>
        <description>Difference measured in BOLD fMRI percent signal change in the left amygdala in fearful versus neutral faces during face processing task.</description>
        <time_frame>Baseline, Day 8</time_frame>
        <population>There were no efficacy evaluations done in this study because of a change in the planned analysis after the study was prematurely terminated due to GCP non-compliance that resulted in data integrity and quality issues.</population>
        <group_list>
          <group group_id="O1">
            <title>PF-04457845</title>
            <description>PF-04457845 4 milligrams (mg) was orally administered once daily in the morning on Days 1 to 7.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to PF-04457845 was orally administered once daily in the morning on Days 1 to 7.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in BOLD fMRI Percent Signal Change in Fearful Versus Neutral Face Contrast in Left Amygdala</title>
          <description>Difference measured in BOLD fMRI percent signal change in the left amygdala in fearful versus neutral faces during face processing task.</description>
          <population>There were no efficacy evaluations done in this study because of a change in the planned analysis after the study was prematurely terminated due to GCP non-compliance that resulted in data integrity and quality issues.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Abnormal Physical Examination Findings</title>
        <description>The full physical examination included head, ears, eyes, nose, mouth, skin, heart, and lung examinations, lymph nodes, gastrointestinal, skeletal, and neurological systems.</description>
        <time_frame>Baseline to up to Day 18</time_frame>
        <population>The safety analysis population included all participants who received study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>PF-04457845</title>
            <description>PF-04457845 4 milligrams (mg) was orally administered once daily in the morning on Days 1 to 7.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to PF-04457845 was orally administered once daily in the morning on Days 1 to 7.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Abnormal Physical Examination Findings</title>
          <description>The full physical examination included head, ears, eyes, nose, mouth, skin, heart, and lung examinations, lymph nodes, gastrointestinal, skeletal, and neurological systems.</description>
          <population>The safety analysis population included all participants who received study medication.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Withdrawals Due to AEs</title>
        <description>An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last study drug administration that were absent before treatment or that worsened relative to pretreatment state. AEs included non-serious AEs and SAEs.</description>
        <time_frame>Baseline up to 28 days after last study drug administration (Day 35)</time_frame>
        <population>The safety analysis population included all participants who received study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>PF-04457845</title>
            <description>PF-04457845 4 milligrams (mg) was orally administered once daily in the morning on Days 1 to 7.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to PF-04457845 was orally administered once daily in the morning on Days 1 to 7.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Withdrawals Due to AEs</title>
          <description>An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last study drug administration that were absent before treatment or that worsened relative to pretreatment state. AEs included non-serious AEs and SAEs.</description>
          <population>The safety analysis population included all participants who received study medication.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Number of Participants with AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number of Participants with SAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number of Participants Discontinued Due to AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Clinical Laboratory Values Meeting Criteria for Potential Clinical Concern</title>
        <description>The following laboratory parameters were analyzed: hematology (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes; liver function (aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium, bicarbonate); chemistry (glucose); urinalysis (dipstick) (urine pH, urine glucose, urine protein, urine blood, urine ketones, urine bilirubin, urine nitrite, urine leukocyte esterase); urinalysis microscopy (urine red blood cell, urine white blood cell, urine bacteria). Only parameters with abnormal values were reported.</description>
        <time_frame>Baseline up to Day 18</time_frame>
        <population>The safety analysis population included all participants who received study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>PF-04457845</title>
            <description>PF-04457845 4 milligrams (mg) was orally administered once daily in the morning on Days 1 to 7.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to PF-04457845 was orally administered once daily in the morning on Days 1 to 7.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Clinical Laboratory Values Meeting Criteria for Potential Clinical Concern</title>
          <description>The following laboratory parameters were analyzed: hematology (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes; liver function (aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium, bicarbonate); chemistry (glucose); urinalysis (dipstick) (urine pH, urine glucose, urine protein, urine blood, urine ketones, urine bilirubin, urine nitrite, urine leukocyte esterase); urinalysis microscopy (urine red blood cell, urine white blood cell, urine bacteria). Only parameters with abnormal values were reported.</description>
          <population>The safety analysis population included all participants who received study medication.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Total neutrophils &lt;0.8 times lower limit of normal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Urine positive for nitrite</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Urine positive for leukocyte esterase</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern</title>
        <description>Vital signs assessment included pulse rate and blood pressure. Criteria for vital sign values meeting potential clinical concern included: supine pulse rate &lt;40 or &gt;120 beats per minute (bpm), standing pulse rate &lt;40 or &gt;140 bpm; systolic blood pressure (SBP) of &gt;=30 millimeters of mercury (mmHg) change from baseline or SBP &lt;90 mmHg; diastolic blood pressure (DBP) &gt;=20 mmHg change from baseline or DBP &lt;50 mmHg.</description>
        <time_frame>Baseline up to Day 18</time_frame>
        <population>The safety analysis population included all participants who received study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>PF-04457845</title>
            <description>PF-04457845 4 milligrams (mg) was orally administered once daily in the morning on Days 1 to 7.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to PF-04457845 was orally administered once daily in the morning on Days 1 to 7.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern</title>
          <description>Vital signs assessment included pulse rate and blood pressure. Criteria for vital sign values meeting potential clinical concern included: supine pulse rate &lt;40 or &gt;120 beats per minute (bpm), standing pulse rate &lt;40 or &gt;140 bpm; systolic blood pressure (SBP) of &gt;=30 millimeters of mercury (mmHg) change from baseline or SBP &lt;90 mmHg; diastolic blood pressure (DBP) &gt;=20 mmHg change from baseline or DBP &lt;50 mmHg.</description>
          <population>The safety analysis population included all participants who received study medication.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Supine SBP &lt;90 mmHg</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Standing SBP &lt;90 mmHg</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Supine DBP &lt;50 mmHg</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Standing DBP &lt;50 mmHg</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Supine Pulse Rate &lt;40 or &gt;120 bpm</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Standing Pulse Rate &lt;40 or &gt;140 bpm</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Supine SBP &gt;=30 mmHg Increase From Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Standing SBP &gt;=30 mmHg Increase From Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Supine DBP &gt;=20 mmHg Increase From Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Standing DBP &gt;=20 mmHg Increase From Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Supine SBP &gt;=30 mmHg Decrease From Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Standing SBP &gt;=30 mmHg Decrease From Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Supine DBP &gt;=20 mmHg Decrease From Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Standing DBP &gt;=20 mmHg Decrease From Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Post-Baseline Electrocardiogram (ECG) Values Meeting Criteria of Potential Clinical Concern</title>
        <description>ECG criteria of potential clinical concern were QTc absolute value &gt;=450 milliseconds (msec) or QTc absolute change &gt;=30 msec.</description>
        <time_frame>Baseline up to Day 18</time_frame>
        <population>The safety analysis population included all participants who received study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>PF-04457845</title>
            <description>PF-04457845 4 milligrams (mg) was orally administered once daily in the morning on Days 1 to 7.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to PF-04457845 was orally administered once daily in the morning on Days 1 to 7.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Post-Baseline Electrocardiogram (ECG) Values Meeting Criteria of Potential Clinical Concern</title>
          <description>ECG criteria of potential clinical concern were QTc absolute value &gt;=450 milliseconds (msec) or QTc absolute change &gt;=30 msec.</description>
          <population>The safety analysis population included all participants who received study medication.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>QTcF Interval 450-&lt;480 msec</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QTcF Interval 480-&lt;500 msec</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QTcF Interval &gt;=500 msec</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QTcF Interval &gt;=30 msec Increase From Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>PF-04457845</title>
          <description>PF-04457845 4 milligrams (mg) was orally administered once daily in the morning on Days 1 to 7.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo matched to PF-04457845 was orally administered once daily in the morning on Days 1 to 7.</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="0"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 18.1</default_vocab>
        <default_assessment>Non-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="6" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest discomfort</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Post procedural haematoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Migraine</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Sleep paralysis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Affect lability</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Flashback</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Post-traumatic stress disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>Restriction Description: Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>There were no efficacy evaluations done in this study because of a change in the planned analysis after the study was prematurely terminated due to GCP non-compliance that resulted in data integrity and quality issues.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Pfizer ClinicalTrials.gov Call Center</name_or_title>
      <organization>Pfizer, Inc.</organization>
      <phone>1-800-718-1021</phone>
      <email>ClinicalTrials.gov_Inquiries@pfizer.com</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/NCT02216097
org study id: B0541013
nct id: NCT02216097
lead sponsor: 
has dmc: No
The purpose of the study is to evaluate proof of mechanism of PF-04457845, using a
      well-established neuroimaging paradigm including behavioral tasks selected to activate
      neuro-circuitry relevant to Post Traumatic Stress Disorder. It is hypothesized that
      PF-04457845 will modulate the Blood-oxygen-level dependent Functional Magnetic Resonance
      Imaging signal from the relevant neuro-circuits in patients with Post Traumatic Stress
      Disorder.
This is a Phase II, randomized, placebo-controlled, parallel group design study in male and
      female subjects with moderate-to-severe Post Traumatic Stress Disorder between the ages of 18
      and 60 years old. During this study, a dose of 4 mg PF-04457845 will be administered in the
      morning on Days 1-7. On Each subject will undergo a resting state fMRI (pre and post and day
      8), a fearful vs. neutral faces fMRI task and a fear extinction fMRI paradigm. The Emotional
      Faces Paradigm and resting state tasks will be performed on Day 1 (prior to drug or placebo)
      and on Day 8. Acquisition of fear conditioning will be performed during the first imaging
      session on Day 1. After the first imaging session on Day 1, subjects will complete behavioral
      rating scales and then be dosed. Approximately six hours after dosing subjects will re-enter
      the scanner and perform the fear extinction paradigm. On Day 2, subjects will perform the
      fear extinction memory retention task within the scanner. Further physiological monitoring,
      including skin conductance and heart rate, will take place during the fear extinction
      paradigm. One safety follow-up visit will occur between Days 11-18.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change From Baseline Blood-Oxygen-Level Dependent (BOLD) Functional Magnetic Resonance Imaging fMRI) Percent Signal Change in Fearful Versus Neutral Face Contrast in Bilateral Amygdala
time frame: Baseline, Day 8
description: Baseline BOLD fMRI percent signal change measured from baseline in fearful versus neutral face contrast during the emotional face processing task in bilateral amygdala.
measure: Change From Baseline in BOLD fMRI Percent Activation in Bilateral Ventromedial Pre-Frontal Cortex (vmPFC)
time frame: Baseline, Day 2
description: Difference measured in BOLD fMRI percent activation in the bilateral vmPFC during the fear extinction recall phase of the fear extinction paradigm.
measure: Change From Baseline in BOLD fMRI Percent Signal Change in Fearful Versus Neutral Face Contrast in Right Amygdala
time frame: Baseline, Day 8
description: Difference measured in BOLD fMRI percent signal change in the right amygdala in fear versus neutral faces during the emotional face processing task.
measure: Change From Baseline in BOLD fMRI Percent Signal Change in Fearful Versus Neutral Face Contrast in Left Amygdala
time frame: Baseline, Day 8
description: Difference measured in BOLD fMRI percent signal change in the left amygdala in fearful versus neutral faces during face processing task.
measure: Number of Participants With Abnormal Physical Examination Findings
time frame: Baseline to up to Day 18
description: The full physical examination included head, ears, eyes, nose, mouth, skin, heart, and lung examinations, lymph nodes, gastrointestinal, skeletal, and neurological systems.
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Withdrawals Due to AEs
time frame: Baseline up to 28 days after last study drug administration (Day 35)
description: An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last study drug administration that were absent before treatment or that worsened relative to pretreatment state. AEs included non-serious AEs and SAEs.
measure: Number of Participants With Clinical Laboratory Values Meeting Criteria for Potential Clinical Concern
time frame: Baseline up to Day 18
description: The following laboratory parameters were analyzed: hematology (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes; liver function (aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium, bicarbonate); chemistry (glucose); urinalysis (dipstick) (urine pH, urine glucose, urine protein, urine blood, urine ketones, urine bilirubin, urine nitrite, urine leukocyte esterase); urinalysis microscopy (urine red blood cell, urine white blood cell, urine bacteria). Only parameters with abnormal values were reported.
measure: Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern
time frame: Baseline up to Day 18
description: Vital signs assessment included pulse rate and blood pressure. Criteria for vital sign values meeting potential clinical concern included: supine pulse rate <40 or >120 beats per minute (bpm), standing pulse rate <40 or >140 bpm; systolic blood pressure (SBP) of >=30 millimeters of mercury (mmHg) change from baseline or SBP <90 mmHg; diastolic blood pressure (DBP) >=20 mmHg change from baseline or DBP <50 mmHg.
measure: Number of Participants With Post-Baseline Electrocardiogram (ECG) Values Meeting Criteria of Potential Clinical Concern
time frame: Baseline up to Day 18
description: ECG criteria of potential clinical concern were QTc absolute value >=450 milliseconds (msec) or QTc absolute change >=30 msec.
arm group label: Treatment
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: PF-04457845
description: 4mg PF-04457845 tablet taken once daily for 7 days.
arm group label: Treatment
intervention type: Drug
intervention name: Placebo
description: Matching placebo tablet taken once daily for 7 days.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Pfizer CT.gov Call Center
role: Study Director
affiliation: Pfizer
facility: 
facility: 
facility: 
country: United States
url: https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B0541013&StudyName=A%20Study%20To%20Assess%20Effects%20Of%20PF-04457845%20On%20Blood-Oxygen-Level%20Dependent%20Functional%20Magnetic%20Resonance%20Imaging%20In%20Subjects%20With%20Post%20Traum
description: To obtain contact information for a study center near you, click here.
responsible party type: Sponsor
mesh term: Stress Disorders, Traumatic
mesh term: Stress Disorders, Post-Traumatic
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: There were no efficacy evaluations done in this study because of a change in the planned analysis after the study was prematurely terminated due to GCP non-compliance that resulted in data integrity and quality issues.
point of contact: 