<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/NCT02262767</url>
  </required_header>
  <id_info>
    <org_study_id>B7601007</org_study_id>
    <secondary_id>2014-003631-19</secondary_id>
    <nct_id>NCT02262767</nct_id>
  </id_info>
  <brief_title>A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of PF-06649751 Co-administered With Trimethobenzamide Hydrochloride in Healthy Subjects</brief_title>
  <official_title>A Phase 1, Double Blind, Sponsor Open, Randomized, Placebo Controlled, Single Ascending Dose Study To Investigate The Safety, Tolerability, And Pharmacokinetics Of Pf 06649751 Co-administered With Trimethobenzamide Hydrochloride In Healthy Volunteers</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 will test the hypothesis that PF-06649751 with continuous co-administration of&#xD;
      trimethobenzamide hydrochloride (TMB) with will be safe and well tolerated. Single doses of&#xD;
      PF-06649751 will be tested in this study, starting at a low dose and escalating to a dose&#xD;
      projected to be under the current limits for drug concentration.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2014</start_date>
  <completion_date type="Actual">December 2014</completion_date>
  <primary_completion_date type="Actual">December 2014</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>Crossover 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>0 - 4 weeks</time_frame>
    <description>Counts of participants who have treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Relatedness to PF-06649751 will be assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category will be counted once within the category.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Supine and standing vital sign measurements</measure>
    <time_frame>0 - 4 weeks</time_frame>
    <description>Measurement of blood pressure and pulse rate.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Electrocardiogram (ECG)</measure>
    <time_frame>0 - 4 weeks</time_frame>
    <description>Measurement of standard 12-lead ECG, single or triplicate</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Laboratory Test Values of Potential Clinical Importance</measure>
    <time_frame>0 - 4 weeks</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>Maximum Observed Plasma Concentration (Cmax)</measure>
    <time_frame>Day 1</time_frame>
    <description>Maximum plasma concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)</measure>
    <time_frame>Day 1 - 5</time_frame>
    <description>Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Curve From Time Zero to Extrapolated Infinite Time AUCinf</measure>
    <time_frame>Day 1 - 5</time_frame>
    <description>AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time. It is obtained from AUC (0 - t) plus AUC (t - inf).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach Maximum Observed Plasma Concentration (Tmax)</measure>
    <time_frame>Day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Decay Half-Life (t1/2)</measure>
    <time_frame>Day 1 - 5</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>Apparent Oral Clearance (CL/F)</measure>
    <time_frame>Day 1 - 5</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>Apparent Volume of Distribution (Vz/F)</measure>
    <time_frame>Day 1 - 5</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>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Single Ascending Doses Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single doses, given by oral solution, starting at 0.75 mg up to a possible maximum of 3.0 mg. The subject will have been fasted for 10 hours prior to the single dose. For each dosing period, 3 subjects will be given a placebo as a comparator while 6 are given active dose. The subjects will be given concomitant trimethobenzamide hydrochloride for the 3 weeks that the subject is in the CRU. For each of the three periods, subjects will be crossed-over from placebo or PF-06649751. Each PF-06649751 dose is separated by one week.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Single Ascending Doses Cohort 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single doses, given by oral solution, starting at 4.5 mg up to a possible maximum of 9.0 mg. The subject will have been fasted for 10 hours prior to the single dose. For each dosing period, 3 subjects will be given a placebo as a comparator while 6 are given active dose. The subjects will be given concomitant trimethobenzamide hydrochloride for the 3 weeks that the subject is in the CRU. For each of the three periods, subjects will be crossed-over from placebo or PF-06649751. Each PF-06649751 dose is separated by one week.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PF-06649751</intervention_name>
    <description>Experimental Pfizer compound.</description>
    <arm_group_label>Single Ascending Doses Cohort 1</arm_group_label>
    <arm_group_label>Single Ascending Doses Cohort 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trimethobenzamide Hydrochloride</intervention_name>
    <description>Trimethobenzamide Hydrochloride is indicated for the treatment of postoperative nausea and vomiting and for nausea associated with gastroenteritis.</description>
    <arm_group_label>Single Ascending Doses Cohort 1</arm_group_label>
    <arm_group_label>Single Ascending Doses Cohort 2</arm_group_label>
    <other_name>Tigan</other_name>
  </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 (BMI) of 17.5 to 30.5 kg/m2; and a total body weight &gt;50 kg (110 lbs).&#xD;
&#xD;
          -  Evidence of a personally signed and dated informed consent document indicating that&#xD;
             the subject has been informed of all pertinent 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 the time of dosing).&#xD;
&#xD;
          -  Treatment with an investigational drug within 30 days (or as determined by the local&#xD;
             requirement) or 5 half lives preceding the first dose of study medication (whichever&#xD;
             is longer).&#xD;
&#xD;
          -  Other severe acute or chronic medical or psychiatric condition or laboratory&#xD;
             abnormality that may increase the risk associated with study participation or&#xD;
             investigational product administration or may interfere with the interpretation of&#xD;
             study results and, in the judgment of the investigator, would make the subject&#xD;
             inappropriate for entry into this 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>
  <overall_official>
    <last_name>Constantino Kantaridis, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Pfizer</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Belgium Pfizer Clinical Research Unit</name>
      <address>
        <city>Brussels</city>
        <zip>1070</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <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>January 2015</verification_date>
  <study_first_submitted>October 9, 2014</study_first_submitted>
  <study_first_submitted_qc>October 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 13, 2014</study_first_posted>
  <last_update_submitted>January 13, 2015</last_update_submitted>
  <last_update_submitted_qc>January 13, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 14, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Phase 1, Randomized, Double Blind, Placebo-Controlled, Single-Dose Escalation, Safety, Tolerability, Pharmacokinetic, PF-06649751, Trimethobenzamide</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Trimethobenzamide</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/NCT02262767
org study id: B7601007
secondary id: 2014-003631-19
nct id: NCT02262767
lead sponsor: 
has dmc: No
This study will test the hypothesis that PF-06649751 with continuous co-administration of
      trimethobenzamide hydrochloride (TMB) with will be safe and well tolerated. Single doses of
      PF-06649751 will be tested in this study, starting at a low dose and escalating to a dose
      projected to be under the current limits for drug concentration.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
time frame: 0 - 4 weeks
description: Counts of participants who have treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Relatedness to PF-06649751 will be assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category will be counted once within the category.
measure: Supine and standing vital sign measurements
time frame: 0 - 4 weeks
description: Measurement of blood pressure and pulse rate.
measure: Electrocardiogram (ECG)
time frame: 0 - 4 weeks
description: Measurement of standard 12-lead ECG, single or triplicate
measure: Number of Participants With Laboratory Test Values of Potential Clinical Importance
time frame: 0 - 4 weeks
description: Pre-defined criteria were established for each laboratory test to define the values that would be identified as of potential clinical importance.
measure: Maximum Observed Plasma Concentration (Cmax)
time frame: Day 1
description: Maximum plasma concentration
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
time frame: Day 1 - 5
description: Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time AUCinf
time frame: Day 1 - 5
description: AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time. It is obtained from AUC (0 - t) plus AUC (t - inf).
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
time frame: Day 1
measure: Plasma Decay Half-Life (t1/2)
time frame: Day 1 - 5
description: Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
measure: Apparent Oral Clearance (CL/F)
time frame: Day 1 - 5
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: Apparent Volume of Distribution (Vz/F)
time frame: Day 1 - 5
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.
arm group label: Single Ascending Doses Cohort 1
arm group type: Experimental
description: Single doses, given by oral solution, starting at 0.75 mg up to a possible maximum of 3.0 mg. The subject will have been fasted for 10 hours prior to the single dose. For each dosing period, 3 subjects will be given a placebo as a comparator while 6 are given active dose. The subjects will be given concomitant trimethobenzamide hydrochloride for the 3 weeks that the subject is in the CRU. For each of the three periods, subjects will be crossed-over from placebo or PF-06649751. Each PF-06649751 dose is separated by one week.
arm group label: Single Ascending Doses Cohort 2
arm group type: Experimental
description: Single doses, given by oral solution, starting at 4.5 mg up to a possible maximum of 9.0 mg. The subject will have been fasted for 10 hours prior to the single dose. For each dosing period, 3 subjects will be given a placebo as a comparator while 6 are given active dose. The subjects will be given concomitant trimethobenzamide hydrochloride for the 3 weeks that the subject is in the CRU. For each of the three periods, subjects will be crossed-over from placebo or PF-06649751. Each PF-06649751 dose is separated by one week.
intervention type: Drug
intervention name: PF-06649751
description: Experimental Pfizer compound.
arm group label: Single Ascending Doses Cohort 1
arm group label: Single Ascending Doses Cohort 2
intervention type: Drug
intervention name: Trimethobenzamide Hydrochloride
description: Trimethobenzamide Hydrochloride is indicated for the treatment of postoperative nausea and vomiting and for nausea associated with gastroenteritis.
arm group label: Single Ascending Doses Cohort 1
arm group label: Single Ascending Doses Cohort 2
other name: Tigan
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
last name: Constantino Kantaridis, MD
role: Principal Investigator
affiliation: Pfizer
facility: 
facility: 
country: Belgium
responsible party type: Sponsor
mesh term: Trimethobenzamide