<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/NCT03796182</url>
  </required_header>
  <id_info>
    <org_study_id>B7451034</org_study_id>
    <secondary_id>DDI</secondary_id>
    <secondary_id>2018-003683-31</secondary_id>
    <nct_id>NCT03796182</nct_id>
  </id_info>
  <brief_title>Study of PF 04965842 Effect on MATE1/2K Activity in Healthy Participants</brief_title>
  <official_title>A PHASE 1, RANDOMIZED, 2-WAY CROSSOVER, OPEN LABEL STUDY TO ESTIMATE THE EFFECT OF PF-04965842 ON MATE1/2K ACTIVITY, USING METFORMIN AS A PROBE, IN HEALTHY PARTICIPANTS</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>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase 1, randomized, 2 way crossover, open label study of the effect of PF-04965842&#xD;
      on metformin (a probe for MATE1/2K activity) PK in healthy adult participants. The effect of&#xD;
      PF-04965842 on N1-methylnicotinamide (NMN; an endogenous biomarker for MATE1/2K) PK and its&#xD;
      correlation to the effect on metformin PK will also be assessed. Participants will be&#xD;
      randomized to 1 of 2 treatment sequences as described below. A total of 12 healthy male&#xD;
      and/or female participants will be enrolled in the study so that 6 participants will be&#xD;
      enrolled in each treatment sequence. Each treatment sequence will consist of 2 periods.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 1, randomized, 2 way crossover, open label study of the effect of PF-04965842&#xD;
      on metformin (a probe for MATE1/2K activity) PK in healthy adult participants. The effect of&#xD;
      PF-04965842 on N1-methylnicotinamide (NMN; an endogenous biomarker for MATE1/2K) PK and its&#xD;
      correlation to the effect on metformin PK will also be assessed. Participants will be&#xD;
      randomized to 1 of 2 treatment sequences as described below. A total of 12 healthy male&#xD;
      and/or female participants will be enrolled in the study so that 6 participants will be&#xD;
      enrolled in each treatment sequence. Each treatment sequence will consist of 2 periods.&#xD;
      Participants who discontinue from the study may be replaced at the sponsor's discretion. The&#xD;
      replacement participant will receive the same treatment sequence as the participant who&#xD;
      discontinued.&#xD;
&#xD;
      Participants will be screened within 28 days of the first dose of investigational product.&#xD;
      Participants will report to the clinical research unit (CRU) the day prior to Day 1 (ie Day&#xD;
      -1) dosing in Period 1 for both treatment sequences. In both sequences, participants will&#xD;
      remain in the CRU for a total of 8 days and 7 nights (including Period 1 and Period 2). There&#xD;
      will be a minimum 4 day washout period between metformin dosing events. NMN and metformin PK&#xD;
      will be assessed in plasma and urine over 24 and 48 hours, respectively.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 10, 2019</start_date>
  <completion_date type="Actual">March 12, 2019</completion_date>
  <primary_completion_date type="Actual">February 13, 2019</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>
    <intervention_model_description>This is a Phase 1, randomized, 2 way crossover, open label study of the effect of PF 04965842 on metformin PK in healthy adult participants. The effect of PF 04965842 on N1 methylnicotinamide (NMN) PK and its correlation to the effect on metformin PK will also be assessed.&#xD;
A total of approximately 12 healthy male and/or female participants will be enrolled in the study so that approximately 6 participants will be enrolled in each treatment sequence. Each treatment sequence will consist of 2 periods. Participants who discontinue from the study may be replaced at the sponsor's discretion. The replacement participant will receive the same treatment sequence as the participant who discontinued.&#xD;
Participants will be screened within 28 days of the first dose of investigational product. Participants will report to the clinical research unit (CRU) the day prior to Day 1 (ie Day -1) dosing in Period 1 for both treatment sequences. In both sequences, participants will remain in the CRU for</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Renal Clearance (CLr) of Metformin</measure>
    <time_frame>For both Period 1 and Period 2 at intervals of 0-12, 12-24, 24-36, and 36-48 hours post metformin dose</time_frame>
    <description>CLr was calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Metformin</measure>
    <time_frame>Pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose of metformin on Day 1 for both Period 1 and Period 2</time_frame>
    <description>AUCinf is a measure of the serum concentration of the drug over time. It was used to characterize drug absorption.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Plasma Concentration (Cmax) of Metformin</measure>
    <time_frame>Pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose of metformin on Day 1 for both Period 1 and Period 2</time_frame>
    <description>Cmax is maximum observed plasma concentration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time for Cmax (Tmax) of Metformin</measure>
    <time_frame>Pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose of metformin on Day 1 for both Period 1 and Period 2</time_frame>
    <description>Tmax of metformin administrated with or without PF-04965842.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration Time Profile From Time 0 to the Time of Last Quantifiable Concentration (AUClast) of Metformin</measure>
    <time_frame>Pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose of metformin on Day 1 for both Period 1 and Period 2</time_frame>
    <description>AUClast of metformin administrated with or without PF-04965842.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Clearance (CL/F) of Metformin</measure>
    <time_frame>Pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose of metformin on Day 1 for both Period 1 and Period 2</time_frame>
    <description>CL/F is a quantitative measure of the rate at which drug was removed from the blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Volume of Distribution (Vz/F) of Metformin</measure>
    <time_frame>Pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose of metformin on Day 1 for both Period 1 and Period 2</time_frame>
    <description>Vz/F 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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal Half-life (t1/2) of Metformin</measure>
    <time_frame>Pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose of metformin on Day 1 for both Period 1 and Period 2</time_frame>
    <description>t1/2 is the time measured for the plasma concentration to decrease by one half.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative Amount of Drug Recovered Unchanged in Urine From 0 to 48 Hours (Ae) of Metformin</measure>
    <time_frame>For both Period 1 and Period 2 at intervals of 0-12, 12-24, 24-36, and 36-48 hours post metformin dose</time_frame>
    <description>Ae is the cumulative amount of drug recovered unchanged in urine during the dosing interval. Cumulative amount was calculated as sum of urine drug concentration in sample volume for each collection interval. Sample volume = (urine weight in gram [g]/1.020), where 1.020 g/mL is the approximate specific gravity of urine.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent of Dose Recovered Unchanged in Urine From 0 to 24 Hours (Ae%) of Metformin</measure>
    <time_frame>For both Period 1 and Period 2 at intervals of 0-12 and 12-24 hours post metformin dose</time_frame>
    <description>Ae% is percent of dose recovered unchanged in urine from 0 to 24 hours post-dose of metformin.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Laboratory Abnormalities</measure>
    <time_frame>Screening (within 28 days prior to Day 1) to Day 7</time_frame>
    <description>Laboratory parameters included: hematology (hemoglobin, hematocrit, erythrocytes, ery. mean corpuscular volume, ery. mean corpuscular hemoglobin, ery. mean corpuscular HGB concentration, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes, activated partial thromboplastin time, prothrombin time, prothrombin intl. normalized ratio, large unstained cells/leukocytes and large unstained cells), clinical chemistry (bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, protein, albumin, blood urea nitrogen, urea, creatinine, urate, sodium, potassium, chloride, calcium, bicarbonate, urobilinogen and glucose -FASTING), urinalysis (specific gravity, pH, urine glucose, ketones, urine protein, urine hemoglobin, urine bilirubin, nitrite and leukocytes). Clinical significance of laboratory parameters is determined at the investigator's discretion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Categorical Vital Signs Meeting Pre-defined Criteria</measure>
    <time_frame>Screening (within 28 days prior to Day 1) to Day 7</time_frame>
    <description>Criteria for change in vital signs: pulse rate value less than (&lt;) 40 beats per minute (bpm) or value over than (&gt;) 120 bpm, systolic blood pressure (SBP) value &lt; 90 millimeter of mercury (mmHg) or change from baseline (Chg) equal to or over than (≥) 30 mmHg increase or ≥ Chg 30 mmHg decrease, diastolic blood pressure (DBP) value &lt; 50 mmHg or Chg ≥ 20 mmHg increase or Chg ≥ 20 mmHg decrease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) (All Causalities and Treatment-related)</measure>
    <time_frame>Day 1 up to Day 40 (35 days after the last dose of metformin)</time_frame>
    <description>AEs with all causalities were any untoward medical occurrences in a study subject administered a product or medical device which did not necessarily had causal relationship with the treatment or usage. An SAE was an AE resulting in any of the following endpoints or deemed significant for any other reason: death; life threatening (immediate risk of death); inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or considered to be an important medical event. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent are events between first dose of study drug and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Treatment-Emergent AEs and SAEs (All Causalities and Treatment-related)</measure>
    <time_frame>Day 1 up to Day 40 (35 days after the last dose of metformin)</time_frame>
    <description>AEs with all causalities were any untoward medical occurrences in a study subject administered a product or medical device which did not necessarily had causal relationship with the treatment or usage. An SAE was an AE resulting in any of the following endpoints or deemed significant for any other reason: death; life threatening (immediate risk of death); inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or considered to be an important medical event. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent are events between first dose of study drug and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Sequence 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients in sequence 1 will received treatment A (metformin) in Period 1 then complete at least 4 days of washout and continue to period 2 where treatment B (PF-04965842 + metformin) will be administered.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sequence 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients in Sequence 2 will start treatment B (PF-04965842 + metformin) then go through a washout period of at least 4 days and continue to Period 2 where treatment A (metformin) will be administered.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>Commercially available metformin (GLUCOPHAGE®) as 500 mg tablets.</description>
    <arm_group_label>Sequence 1</arm_group_label>
    <arm_group_label>Sequence 2</arm_group_label>
    <other_name>Glucophage</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PF-04965842</intervention_name>
    <description>PF 04965842 100 mg tablets</description>
    <arm_group_label>Sequence 1</arm_group_label>
    <arm_group_label>Sequence 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female participants who are overtly healthy as determined by medical&#xD;
             evaluation including a detailed medical history, complete physical examination,&#xD;
             laboratory tests, and cardiovascular tests.&#xD;
&#xD;
          -  Participants who are willing and able to comply with all scheduled visits, treatment&#xD;
             plan, laboratory tests, lifestyle considerations, and other study procedures.&#xD;
&#xD;
          -  Female participants who are of child bearing potential must not be intending to become&#xD;
             pregnant, currently pregnant, or lactating.&#xD;
&#xD;
          -  Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight &gt;50 kg (110 lb).&#xD;
&#xD;
          -  Capable of giving signed informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Evidence or history of clinically significant hematological, renal, endocrine,&#xD;
             pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or&#xD;
             allergic disease.&#xD;
&#xD;
          -  Any condition possibly affecting drug absorption (eg, gastrectomy).&#xD;
&#xD;
          -  History of human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus&#xD;
             infection; positive testing for HIV, hepatitis B surface antigen (HepBsAg), hepatitis&#xD;
             B core antibody (HepBcAb), or hepatitis C virus antibody (HCVAb).&#xD;
&#xD;
          -  Other acute or chronic medical or psychiatric condition including recent (within the&#xD;
             past year).&#xD;
&#xD;
          -  Evidence or history of clinically significant dermatological condition (eg, atopic&#xD;
             dermatitis or psoriasis) or visible rash present during physical examination.&#xD;
&#xD;
          -  Clinically relevant history of lactic acidosis.&#xD;
&#xD;
          -  Use of prescription or nonprescription drugs and dietary and herbal supplements within&#xD;
             7 days or 5 half lives (whichever is longer) prior to the first dose of&#xD;
             investigational product.&#xD;
&#xD;
          -  A positive urine drug test.&#xD;
&#xD;
          -  Selected laboratory abnormalities.&#xD;
&#xD;
          -  History of regular alcohol consumption exceeding 14 drinks/week for female&#xD;
             participants or 21 drinks/week for male participants (1 drink = 5 ounces [150 mL] of&#xD;
             wine or 12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard liquor) within 6&#xD;
             months before screening.&#xD;
&#xD;
          -  Known relevant history of elevated liver function tests (LFTs).&#xD;
&#xD;
          -  History of tuberculosis (TB) (active or latent)&#xD;
&#xD;
          -  Any history of chronic infections, any history of recurrent infections, any history of&#xD;
             latent infections, or any acute infection within 2 weeks of baseline.&#xD;
&#xD;
          -  History of disseminated herpes zoster, or disseminated herpes simplex, or recurrent&#xD;
             localized dermatomal herpes zoster.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pfizer CT.gov Call Center</last_name>
    <role>Study Director</role>
    <affiliation>Pfizer</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Pfizer Clinical Research Unit</name>
      <address>
        <city>Brussels</city>
        <zip>B-1070</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <link>
    <url>https://pmiform.com/clinical-trial-info-request?StudyID=B7451034</url>
    <description>To obtain contact information for a study center near you, click here.</description>
  </link>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>January 4, 2019</study_first_submitted>
  <study_first_submitted_qc>January 4, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 8, 2019</study_first_posted>
  <results_first_submitted>January 22, 2020</results_first_submitted>
  <results_first_submitted_qc>January 22, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">February 5, 2020</results_first_posted>
  <last_update_submitted>January 22, 2020</last_update_submitted>
  <last_update_submitted_qc>January 22, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 5, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Phase 1</keyword>
  <keyword>Metformin</keyword>
  <keyword>Atopic dermatitis</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
    <mesh_term>Abrocitinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 14, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/82/NCT03796182/SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 1, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/82/NCT03796182/Prot_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>A total of 12 healthy participants were enrolled in the study and 6 participants were assigned in each of the 2 treatment sequences, all receiving study treatment.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Metformin Then Metformin + PF-04965842</title>
          <description>Participants were administered a single oral dose of metformin 500 mg on Day 1 in Period 1 followed by a washout period of at least 4 days. Then in Period 2 participants were administered a single oral dose of metformin 500 mg on Day 1 along with oral doses of PF-04965842 200 mg once daily (QD) for 2 days on Days 1-2.</description>
        </group>
        <group group_id="P2">
          <title>Metformin + PF-04965842 Then Metformin</title>
          <description>Participants were administered a single oral dose of metformin 500 mg on Day 1 along with oral doses of PF-04965842 200 mg QD for 2 days on Days 1-2 in Period 1 followed by a washout period of at least 4 days. Then in Period 2 participants were administered a single oral dose of metformin 500 mg on Day 1.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Period 1</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <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>
          <title>Washout Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <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>
          <title>Period 2</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <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>
      <population>All 12 participants who were randomized to study treatment.</population>
      <group_list>
        <group group_id="B1">
          <title>All Participants</title>
          <description>This reporting group refers to the total 12 participants who were enrolled in the study.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="12"/>
          </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="39.0" spread="8.42"/>
                  </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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Renal Clearance (CLr) of Metformin</title>
        <description>CLr was calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau).</description>
        <time_frame>For both Period 1 and Period 2 at intervals of 0-12, 12-24, 24-36, and 36-48 hours post metformin dose</time_frame>
        <population>This analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. Overall number of participants analyzed referred to participants evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Metformin + PF-04965842</title>
            <description>This reporting group refers to the participants who were randomized to the group of concomitantly single oral administration of metformin 500 mg QD on Day 1 and oral administration of PF-04965842 200 mg QD for 2 days on Days 1-2 in either of the periods.</description>
          </group>
          <group group_id="O2">
            <title>Metformin</title>
            <description>This reporting group refers to the participants who were randomized to the group of single oral administration of metformin 500 mg QD on Day 1 in either of the periods.</description>
          </group>
        </group_list>
        <measure>
          <title>Renal Clearance (CLr) of Metformin</title>
          <description>CLr was calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau).</description>
          <population>This analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. Overall number of participants analyzed referred to participants evaluable for this outcome measure.</population>
          <units>litre per hour (L/hr)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.18" spread="39"/>
                    <measurement group_id="O2" value="33.33" spread="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The corresponding 90% confidence intervals equivalence criteria was (80%, 125%) acceptance range.</non_inferiority_desc>
            <param_type>Ratio</param_type>
            <param_value>98.50</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>82.09</ci_lower_limit>
            <ci_upper_limit>118.20</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Metformin</title>
        <description>AUCinf is a measure of the serum concentration of the drug over time. It was used to characterize drug absorption.</description>
        <time_frame>Pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose of metformin on Day 1 for both Period 1 and Period 2</time_frame>
        <population>This analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. Overall number of participants analyzed referred to participants evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Metformin + PF-04965842</title>
            <description>This reporting group refers to the participants who were randomized to the group of concomitantly single oral administration of metformin 500 mg QD on Day 1 and oral administration of PF-04965842 200 mg QD for 2 days on Days 1-2 in either of the periods.</description>
          </group>
          <group group_id="O2">
            <title>Metformin</title>
            <description>This reporting group refers to the participants who were randomized to the group of single oral administration of metformin 500 mg QD on Day 1 in either of the periods.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Metformin</title>
          <description>AUCinf is a measure of the serum concentration of the drug over time. It was used to characterize drug absorption.</description>
          <population>This analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. Overall number of participants analyzed referred to participants evaluable for this outcome measure.</population>
          <units>nanogram*hour per milliliter (ng*hr/mL)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5050" spread="16"/>
                    <measurement group_id="O2" value="5202" spread="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The corresponding 90% confidence intervals equivalence criteria was (80%, 125%) acceptance range.</non_inferiority_desc>
            <param_type>Ratio</param_type>
            <param_value>93.49</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>85.15</ci_lower_limit>
            <ci_upper_limit>102.65</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Plasma Concentration (Cmax) of Metformin</title>
        <description>Cmax is maximum observed plasma concentration.</description>
        <time_frame>Pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose of metformin on Day 1 for both Period 1 and Period 2</time_frame>
        <population>This analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.</population>
        <group_list>
          <group group_id="O1">
            <title>Metformin + PF-04965842</title>
            <description>This reporting group refers to the participants who were randomized to the group of concomitantly single oral administration of metformin 500 mg QD on Day 1 and oral administration of PF-04965842 200 mg QD for 2 days on Days 1-2 in either of the periods.</description>
          </group>
          <group group_id="O2">
            <title>Metformin</title>
            <description>This reporting group refers to the participants who were randomized to the group of single oral administration of metformin 500 mg QD on Day 1 in either of the periods.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Plasma Concentration (Cmax) of Metformin</title>
          <description>Cmax is maximum observed plasma concentration.</description>
          <population>This analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.</population>
          <units>nanogram per milliliter (ng/mL)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="634.7" spread="14"/>
                    <measurement group_id="O2" value="720.7" spread="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The corresponding 90% confidence intervals equivalence criteria was (80%, 125%) acceptance range.</non_inferiority_desc>
            <param_type>Ratio</param_type>
            <param_value>88.07</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>80.99</ci_lower_limit>
            <ci_upper_limit>95.76</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time for Cmax (Tmax) of Metformin</title>
        <description>Tmax of metformin administrated with or without PF-04965842.</description>
        <time_frame>Pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose of metformin on Day 1 for both Period 1 and Period 2</time_frame>
        <population>This analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.</population>
        <group_list>
          <group group_id="O1">
            <title>Metformin + PF-04965842</title>
            <description>This reporting group refers to the participants who were randomized to the group of concomitantly single oral administration of metformin 500 mg QD on Day 1 and oral administration of PF-04965842 200 mg QD for 2 days on Days 1-2 in either of the periods.</description>
          </group>
          <group group_id="O2">
            <title>Metformin</title>
            <description>This reporting group refers to the participants who were randomized to the group of single oral administration of metformin 500 mg QD on Day 1 in either of the periods.</description>
          </group>
        </group_list>
        <measure>
          <title>Time for Cmax (Tmax) of Metformin</title>
          <description>Tmax of metformin administrated with or without PF-04965842.</description>
          <population>This analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.</population>
          <units>Hours (hrs)</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.00" lower_limit="2.00" upper_limit="4.00"/>
                    <measurement group_id="O2" value="4.00" lower_limit="1.00" upper_limit="4.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration Time Profile From Time 0 to the Time of Last Quantifiable Concentration (AUClast) of Metformin</title>
        <description>AUClast of metformin administrated with or without PF-04965842.</description>
        <time_frame>Pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose of metformin on Day 1 for both Period 1 and Period 2</time_frame>
        <population>This analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.</population>
        <group_list>
          <group group_id="O1">
            <title>Metformin + PF-04965842</title>
            <description>This reporting group refers to the participants who were randomized to the group of concomitantly single oral administration of metformin 500 mg QD on Day 1 and oral administration of PF-04965842 200 mg QD for 2 days on Days 1-2 in either of the periods.</description>
          </group>
          <group group_id="O2">
            <title>Metformin</title>
            <description>This reporting group refers to the participants who were randomized to the group of single oral administration of metformin 500 mg QD on Day 1 in either of the periods.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration Time Profile From Time 0 to the Time of Last Quantifiable Concentration (AUClast) of Metformin</title>
          <description>AUClast of metformin administrated with or without PF-04965842.</description>
          <population>This analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.</population>
          <units>ng*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4849" spread="18"/>
                    <measurement group_id="O2" value="5145" spread="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The corresponding 90% confidence intervals equivalence criteria was (80%, 125%) acceptance range.</non_inferiority_desc>
            <param_type>Ratio</param_type>
            <param_value>94.25</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>88.19</ci_lower_limit>
            <ci_upper_limit>100.73</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Clearance (CL/F) of Metformin</title>
        <description>CL/F is a quantitative measure of the rate at which drug was removed from the blood.</description>
        <time_frame>Pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose of metformin on Day 1 for both Period 1 and Period 2</time_frame>
        <population>This analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. Overall number of participants analyzed referred to participants evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Metformin + PF-04965842</title>
            <description>This reporting group refers to the participants who were randomized to the group of concomitantly single oral administration of metformin 500 mg QD on Day 1 and oral administration of PF-04965842 200 mg QD for 2 days on Days 1-2 in either of the periods.</description>
          </group>
          <group group_id="O2">
            <title>Metformin</title>
            <description>This reporting group refers to the participants who were randomized to the group of single oral administration of metformin 500 mg QD on Day 1 in either of the periods.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Clearance (CL/F) of Metformin</title>
          <description>CL/F is a quantitative measure of the rate at which drug was removed from the blood.</description>
          <population>This analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. Overall number of participants analyzed referred to participants evaluable for this outcome measure.</population>
          <units>L/hr</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="98.97" spread="16"/>
                    <measurement group_id="O2" value="96.13" spread="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Volume of Distribution (Vz/F) of Metformin</title>
        <description>Vz/F 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.</description>
        <time_frame>Pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose of metformin on Day 1 for both Period 1 and Period 2</time_frame>
        <population>This analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. Overall number of participants analyzed referred to participants evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Metformin + PF-04965842</title>
            <description>This reporting group refers to the participants who were randomized to the group of concomitantly single oral administration of metformin 500 mg QD on Day 1 and oral administration of PF-04965842 200 mg QD for 2 days on Days 1-2 in either of the periods.</description>
          </group>
          <group group_id="O2">
            <title>Metformin</title>
            <description>This reporting group refers to the participants who were randomized to the group of single oral administration of metformin 500 mg QD on Day 1 in either of the periods.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Volume of Distribution (Vz/F) of Metformin</title>
          <description>Vz/F 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.</description>
          <population>This analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. Overall number of participants analyzed referred to participants evaluable for this outcome measure.</population>
          <units>liter (L)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1087" spread="42"/>
                    <measurement group_id="O2" value="1211" spread="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Terminal Half-life (t1/2) of Metformin</title>
        <description>t1/2 is the time measured for the plasma concentration to decrease by one half.</description>
        <time_frame>Pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose of metformin on Day 1 for both Period 1 and Period 2</time_frame>
        <population>This analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. Overall number of participants analyzed referred to participants evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Metformin + PF-04965842</title>
            <description>This reporting group refers to the participants who were randomized to the group of concomitantly single oral administration of metformin 500 mg QD on Day 1 and oral administration of PF-04965842 200 mg QD for 2 days on Days 1-2 in either of the periods.</description>
          </group>
          <group group_id="O2">
            <title>Metformin</title>
            <description>This reporting group refers to the participants who were randomized to the group of single oral administration of metformin 500 mg QD on Day 1 in either of the periods.</description>
          </group>
        </group_list>
        <measure>
          <title>Terminal Half-life (t1/2) of Metformin</title>
          <description>t1/2 is the time measured for the plasma concentration to decrease by one half.</description>
          <population>This analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. Overall number of participants analyzed referred to participants evaluable for this outcome measure.</population>
          <units>hrs</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.318" spread="4.2508"/>
                    <measurement group_id="O2" value="9.261" spread="3.5165"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cumulative Amount of Drug Recovered Unchanged in Urine From 0 to 48 Hours (Ae) of Metformin</title>
        <description>Ae is the cumulative amount of drug recovered unchanged in urine during the dosing interval. Cumulative amount was calculated as sum of urine drug concentration in sample volume for each collection interval. Sample volume = (urine weight in gram [g]/1.020), where 1.020 g/mL is the approximate specific gravity of urine.</description>
        <time_frame>For both Period 1 and Period 2 at intervals of 0-12, 12-24, 24-36, and 36-48 hours post metformin dose</time_frame>
        <population>This analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. Overall number of participants analyzed referred to participants evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Metformin + PF-04965842</title>
            <description>This reporting group refers to the participants who were randomized to the group of concomitantly single oral administration of metformin 500 mg QD on Day 1 and oral administration of PF-04965842 200 mg QD for 2 days on Days 1-2 in either of the periods.</description>
          </group>
          <group group_id="O2">
            <title>Metformin</title>
            <description>This reporting group refers to the participants who were randomized to the group of single oral administration of metformin 500 mg QD on Day 1 in either of the periods.</description>
          </group>
        </group_list>
        <measure>
          <title>Cumulative Amount of Drug Recovered Unchanged in Urine From 0 to 48 Hours (Ae) of Metformin</title>
          <description>Ae is the cumulative amount of drug recovered unchanged in urine during the dosing interval. Cumulative amount was calculated as sum of urine drug concentration in sample volume for each collection interval. Sample volume = (urine weight in gram [g]/1.020), where 1.020 g/mL is the approximate specific gravity of urine.</description>
          <population>This analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. Overall number of participants analyzed referred to participants evaluable for this outcome measure.</population>
          <units>milligram (mg)</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="168.0" lower_limit="70.7" upper_limit="210"/>
                    <measurement group_id="O2" value="170.5" lower_limit="114" upper_limit="248"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent of Dose Recovered Unchanged in Urine From 0 to 24 Hours (Ae%) of Metformin</title>
        <description>Ae% is percent of dose recovered unchanged in urine from 0 to 24 hours post-dose of metformin.</description>
        <time_frame>For both Period 1 and Period 2 at intervals of 0-12 and 12-24 hours post metformin dose</time_frame>
        <population>This analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. Overall number of participants analyzed referred to participants evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Metformin + PF-04965842</title>
            <description>This reporting group refers to the participants who were randomized to the group of concomitantly single oral administration of metformin 500 mg QD on Day 1 and oral administration of PF-04965842 200 mg QD for 2 days on Days 1-2 in either of the periods.</description>
          </group>
          <group group_id="O2">
            <title>Metformin</title>
            <description>This reporting group refers to the participants who were randomized to the group of single oral administration of metformin 500 mg QD on Day 1 in either of the periods.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent of Dose Recovered Unchanged in Urine From 0 to 24 Hours (Ae%) of Metformin</title>
          <description>Ae% is percent of dose recovered unchanged in urine from 0 to 24 hours post-dose of metformin.</description>
          <population>This analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. Overall number of participants analyzed referred to participants evaluable for this outcome measure.</population>
          <units>percentage of dose</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.60" lower_limit="14.1" upper_limit="42.0"/>
                    <measurement group_id="O2" value="34.05" lower_limit="22.7" upper_limit="49.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Laboratory Abnormalities</title>
        <description>Laboratory parameters included: hematology (hemoglobin, hematocrit, erythrocytes, ery. mean corpuscular volume, ery. mean corpuscular hemoglobin, ery. mean corpuscular HGB concentration, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes, activated partial thromboplastin time, prothrombin time, prothrombin intl. normalized ratio, large unstained cells/leukocytes and large unstained cells), clinical chemistry (bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, protein, albumin, blood urea nitrogen, urea, creatinine, urate, sodium, potassium, chloride, calcium, bicarbonate, urobilinogen and glucose -FASTING), urinalysis (specific gravity, pH, urine glucose, ketones, urine protein, urine hemoglobin, urine bilirubin, nitrite and leukocytes). Clinical significance of laboratory parameters is determined at the investigator's discretion.</description>
        <time_frame>Screening (within 28 days prior to Day 1) to Day 7</time_frame>
        <population>This analysis population was defined as all participants randomly assigned to investigational product and who took at least 1 dose of investigational product.</population>
        <group_list>
          <group group_id="O1">
            <title>Metformin + PF-04965842</title>
            <description>This reporting group refers to the participants who were randomized to the group of concomitantly single oral administration of metformin 500 mg QD on Day 1 and oral administration of PF-04965842 200 mg QD for 2 days on Days 1-2 in either of the periods.</description>
          </group>
          <group group_id="O2">
            <title>Metformin</title>
            <description>This reporting group refers to the participants who were randomized to the group of single oral administration of metformin 500 mg QD on Day 1 in either of the periods.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Laboratory Abnormalities</title>
          <description>Laboratory parameters included: hematology (hemoglobin, hematocrit, erythrocytes, ery. mean corpuscular volume, ery. mean corpuscular hemoglobin, ery. mean corpuscular HGB concentration, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes, activated partial thromboplastin time, prothrombin time, prothrombin intl. normalized ratio, large unstained cells/leukocytes and large unstained cells), clinical chemistry (bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, protein, albumin, blood urea nitrogen, urea, creatinine, urate, sodium, potassium, chloride, calcium, bicarbonate, urobilinogen and glucose -FASTING), urinalysis (specific gravity, pH, urine glucose, ketones, urine protein, urine hemoglobin, urine bilirubin, nitrite and leukocytes). Clinical significance of laboratory parameters is determined at the investigator's discretion.</description>
          <population>This analysis population was defined as all participants randomly assigned to investigational product and who took at least 1 dose of investigational product.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
              </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 Categorical Vital Signs Meeting Pre-defined Criteria</title>
        <description>Criteria for change in vital signs: pulse rate value less than (&lt;) 40 beats per minute (bpm) or value over than (&gt;) 120 bpm, systolic blood pressure (SBP) value &lt; 90 millimeter of mercury (mmHg) or change from baseline (Chg) equal to or over than (≥) 30 mmHg increase or ≥ Chg 30 mmHg decrease, diastolic blood pressure (DBP) value &lt; 50 mmHg or Chg ≥ 20 mmHg increase or Chg ≥ 20 mmHg decrease.</description>
        <time_frame>Screening (within 28 days prior to Day 1) to Day 7</time_frame>
        <population>This analysis population was defined as all participants randomly assigned to investigational product and who took at least 1 dose of investigational product.</population>
        <group_list>
          <group group_id="O1">
            <title>Metformin + PF-04965842</title>
            <description>This reporting group refers to the participants who were randomized to the group of concomitantly single oral administration of metformin 500 mg QD on Day 1 and oral administration of PF-04965842 200 mg QD for 2 days on Days 1-2 in either of the periods.</description>
          </group>
          <group group_id="O2">
            <title>Metformin</title>
            <description>This reporting group refers to the participants who were randomized to the group of single oral administration of metformin 500 mg QD on Day 1 in either of the periods.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Categorical Vital Signs Meeting Pre-defined Criteria</title>
          <description>Criteria for change in vital signs: pulse rate value less than (&lt;) 40 beats per minute (bpm) or value over than (&gt;) 120 bpm, systolic blood pressure (SBP) value &lt; 90 millimeter of mercury (mmHg) or change from baseline (Chg) equal to or over than (≥) 30 mmHg increase or ≥ Chg 30 mmHg decrease, diastolic blood pressure (DBP) value &lt; 50 mmHg or Chg ≥ 20 mmHg increase or Chg ≥ 20 mmHg decrease.</description>
          <population>This analysis population was defined as all participants randomly assigned to investigational product and who took at least 1 dose of investigational product.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Supine DBP Value &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 DBP Chg ≥ 20 mmHg increase</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 Chg ≥ 20 mmHg decrease</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 Value &lt; 40 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 pulse rate Value &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>Supine SBP Value &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 SBP Chg ≥ 30 mmHg increase</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 Chg ≥ 30 mmHg decrease</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 Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) (All Causalities and Treatment-related)</title>
        <description>AEs with all causalities were any untoward medical occurrences in a study subject administered a product or medical device which did not necessarily had causal relationship with the treatment or usage. An SAE was an AE resulting in any of the following endpoints or deemed significant for any other reason: death; life threatening (immediate risk of death); inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or considered to be an important medical event. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent are events between first dose of study drug and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state.</description>
        <time_frame>Day 1 up to Day 40 (35 days after the last dose of metformin)</time_frame>
        <population>This analysis population was defined as all participants randomly assigned to investigational product and who took at least 1 dose of investigational product.</population>
        <group_list>
          <group group_id="O1">
            <title>Metformin + PF-04965842</title>
            <description>This reporting group refers to the participants who were randomized to the group of concomitantly single oral administration of metformin 500 mg QD on Day 1 and oral administration of PF-04965842 200 mg QD for 2 days on Days 1-2 in either of the periods.</description>
          </group>
          <group group_id="O2">
            <title>Metformin</title>
            <description>This reporting group refers to the participants who were randomized to the group of single oral administration of metformin 500 mg QD on Day 1 in either of the periods.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) (All Causalities and Treatment-related)</title>
          <description>AEs with all causalities were any untoward medical occurrences in a study subject administered a product or medical device which did not necessarily had causal relationship with the treatment or usage. An SAE was an AE resulting in any of the following endpoints or deemed significant for any other reason: death; life threatening (immediate risk of death); inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or considered to be an important medical event. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent are events between first dose of study drug and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state.</description>
          <population>This analysis population was defined as all participants randomly assigned to investigational product and who took at least 1 dose of investigational product.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AEs (all causalities)</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>AEs (treatment-related)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SAEs (all causalities)</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>SAEs (treatment-related)</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>Percentage of Participants With Treatment-Emergent AEs and SAEs (All Causalities and Treatment-related)</title>
        <description>AEs with all causalities were any untoward medical occurrences in a study subject administered a product or medical device which did not necessarily had causal relationship with the treatment or usage. An SAE was an AE resulting in any of the following endpoints or deemed significant for any other reason: death; life threatening (immediate risk of death); inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or considered to be an important medical event. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent are events between first dose of study drug and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state.</description>
        <time_frame>Day 1 up to Day 40 (35 days after the last dose of metformin)</time_frame>
        <population>This analysis population was defined as all participants randomly assigned to investigational product and who took at least 1 dose of investigational product.</population>
        <group_list>
          <group group_id="O1">
            <title>Metformin + PF-04965842</title>
            <description>This reporting group refers to the participants who were randomized to the group of concomitantly single oral administration of metformin 500 mg QD on Day 1 and oral administration of PF-04965842 200 mg QD for 2 days on Days 1-2 in either of the periods.</description>
          </group>
          <group group_id="O2">
            <title>Metformin</title>
            <description>This reporting group refers to the participants who were randomized to the group of single oral administration of metformin 500 mg QD on Day 1 in either of the periods.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Treatment-Emergent AEs and SAEs (All Causalities and Treatment-related)</title>
          <description>AEs with all causalities were any untoward medical occurrences in a study subject administered a product or medical device which did not necessarily had causal relationship with the treatment or usage. An SAE was an AE resulting in any of the following endpoints or deemed significant for any other reason: death; life threatening (immediate risk of death); inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or considered to be an important medical event. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent are events between first dose of study drug and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state.</description>
          <population>This analysis population was defined as all participants randomly assigned to investigational product and who took at least 1 dose of investigational product.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AEs (all causalities)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50.0"/>
                    <measurement group_id="O2" value="33.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AEs (treatment-related)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.7"/>
                    <measurement group_id="O2" value="33.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SAEs (all causalities)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SAEs (treatment-related)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Day 1 up to Day 40 (35 days after the last dose of metformin)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Metformin + PF-04965842</title>
          <description>This reporting group refers to the participants who were randomized to the group of concomitantly single oral administration of metformin 500 mg QD on Day 1 and oral administration of PF-04965842 200 mg QD for 2 days on Days 1-2 in either of the periods.</description>
        </group>
        <group group_id="E2">
          <title>Metformin</title>
          <description>This reporting group refers to the participants who were randomized to the group of single oral administration of metformin 500 mg QD on Day 1 in either of the periods.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA v21.1</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="12"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="12"/>
              </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="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Anorectal discomfort</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="12"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>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>
    <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_Inquires@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/NCT03796182
org study id: B7451034
secondary id: DDI
secondary id: 2018-003683-31
nct id: NCT03796182
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase 1, randomized, 2 way crossover, open label study of the effect of PF-04965842
      on metformin (a probe for MATE1/2K activity) PK in healthy adult participants. The effect of
      PF-04965842 on N1-methylnicotinamide (NMN; an endogenous biomarker for MATE1/2K) PK and its
      correlation to the effect on metformin PK will also be assessed. Participants will be
      randomized to 1 of 2 treatment sequences as described below. A total of 12 healthy male
      and/or female participants will be enrolled in the study so that 6 participants will be
      enrolled in each treatment sequence. Each treatment sequence will consist of 2 periods.
This is a Phase 1, randomized, 2 way crossover, open label study of the effect of PF-04965842
      on metformin (a probe for MATE1/2K activity) PK in healthy adult participants. The effect of
      PF-04965842 on N1-methylnicotinamide (NMN; an endogenous biomarker for MATE1/2K) PK and its
      correlation to the effect on metformin PK will also be assessed. Participants will be
      randomized to 1 of 2 treatment sequences as described below. A total of 12 healthy male
      and/or female participants will be enrolled in the study so that 6 participants will be
      enrolled in each treatment sequence. Each treatment sequence will consist of 2 periods.
      Participants who discontinue from the study may be replaced at the sponsor's discretion. The
      replacement participant will receive the same treatment sequence as the participant who
      discontinued.

      Participants will be screened within 28 days of the first dose of investigational product.
      Participants will report to the clinical research unit (CRU) the day prior to Day 1 (ie Day
      -1) dosing in Period 1 for both treatment sequences. In both sequences, participants will
      remain in the CRU for a total of 8 days and 7 nights (including Period 1 and Period 2). There
      will be a minimum 4 day washout period between metformin dosing events. NMN and metformin PK
      will be assessed in plasma and urine over 24 and 48 hours, respectively.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: This is a Phase 1, randomized, 2 way crossover, open label study of the effect of PF 04965842 on metformin PK in healthy adult participants. The effect of PF 04965842 on N1 methylnicotinamide (NMN) PK and its correlation to the effect on metformin PK will also be assessed.
A total of approximately 12 healthy male and/or female participants will be enrolled in the study so that approximately 6 participants will be enrolled in each treatment sequence. Each treatment sequence will consist of 2 periods. Participants who discontinue from the study may be replaced at the sponsor's discretion. The replacement participant will receive the same treatment sequence as the participant who discontinued.
Participants will be screened within 28 days of the first dose of investigational product. Participants will report to the clinical research unit (CRU) the day prior to Day 1 (ie Day -1) dosing in Period 1 for both treatment sequences. In both sequences, participants will remain in the CRU for
primary purpose: Treatment
masking: None (Open Label)
measure: Renal Clearance (CLr) of Metformin
time frame: For both Period 1 and Period 2 at intervals of 0-12, 12-24, 24-36, and 36-48 hours post metformin dose
description: CLr was calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau).
measure: Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Metformin
time frame: Pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose of metformin on Day 1 for both Period 1 and Period 2
description: AUCinf is a measure of the serum concentration of the drug over time. It was used to characterize drug absorption.
measure: Maximum Plasma Concentration (Cmax) of Metformin
time frame: Pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose of metformin on Day 1 for both Period 1 and Period 2
description: Cmax is maximum observed plasma concentration.
measure: Time for Cmax (Tmax) of Metformin
time frame: Pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose of metformin on Day 1 for both Period 1 and Period 2
description: Tmax of metformin administrated with or without PF-04965842.
measure: Area Under the Plasma Concentration Time Profile From Time 0 to the Time of Last Quantifiable Concentration (AUClast) of Metformin
time frame: Pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose of metformin on Day 1 for both Period 1 and Period 2
description: AUClast of metformin administrated with or without PF-04965842.
measure: Apparent Clearance (CL/F) of Metformin
time frame: Pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose of metformin on Day 1 for both Period 1 and Period 2
description: CL/F is a quantitative measure of the rate at which drug was removed from the blood.
measure: Apparent Volume of Distribution (Vz/F) of Metformin
time frame: Pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose of metformin on Day 1 for both Period 1 and Period 2
description: Vz/F 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.
measure: Terminal Half-life (t1/2) of Metformin
time frame: Pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose of metformin on Day 1 for both Period 1 and Period 2
description: t1/2 is the time measured for the plasma concentration to decrease by one half.
measure: Cumulative Amount of Drug Recovered Unchanged in Urine From 0 to 48 Hours (Ae) of Metformin
time frame: For both Period 1 and Period 2 at intervals of 0-12, 12-24, 24-36, and 36-48 hours post metformin dose
description: Ae is the cumulative amount of drug recovered unchanged in urine during the dosing interval. Cumulative amount was calculated as sum of urine drug concentration in sample volume for each collection interval. Sample volume = (urine weight in gram [g]/1.020), where 1.020 g/mL is the approximate specific gravity of urine.
measure: Percent of Dose Recovered Unchanged in Urine From 0 to 24 Hours (Ae%) of Metformin
time frame: For both Period 1 and Period 2 at intervals of 0-12 and 12-24 hours post metformin dose
description: Ae% is percent of dose recovered unchanged in urine from 0 to 24 hours post-dose of metformin.
measure: Number of Participants With Laboratory Abnormalities
time frame: Screening (within 28 days prior to Day 1) to Day 7
description: Laboratory parameters included: hematology (hemoglobin, hematocrit, erythrocytes, ery. mean corpuscular volume, ery. mean corpuscular hemoglobin, ery. mean corpuscular HGB concentration, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes, activated partial thromboplastin time, prothrombin time, prothrombin intl. normalized ratio, large unstained cells/leukocytes and large unstained cells), clinical chemistry (bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, protein, albumin, blood urea nitrogen, urea, creatinine, urate, sodium, potassium, chloride, calcium, bicarbonate, urobilinogen and glucose -FASTING), urinalysis (specific gravity, pH, urine glucose, ketones, urine protein, urine hemoglobin, urine bilirubin, nitrite and leukocytes). Clinical significance of laboratory parameters is determined at the investigator's discretion.
measure: Number of Participants With Categorical Vital Signs Meeting Pre-defined Criteria
time frame: Screening (within 28 days prior to Day 1) to Day 7
description: Criteria for change in vital signs: pulse rate value less than (<) 40 beats per minute (bpm) or value over than (>) 120 bpm, systolic blood pressure (SBP) value < 90 millimeter of mercury (mmHg) or change from baseline (Chg) equal to or over than (≥) 30 mmHg increase or ≥ Chg 30 mmHg decrease, diastolic blood pressure (DBP) value < 50 mmHg or Chg ≥ 20 mmHg increase or Chg ≥ 20 mmHg decrease.
measure: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) (All Causalities and Treatment-related)
time frame: Day 1 up to Day 40 (35 days after the last dose of metformin)
description: AEs with all causalities were any untoward medical occurrences in a study subject administered a product or medical device which did not necessarily had causal relationship with the treatment or usage. An SAE was an AE resulting in any of the following endpoints or deemed significant for any other reason: death; life threatening (immediate risk of death); inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or considered to be an important medical event. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent are events between first dose of study drug and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
measure: Percentage of Participants With Treatment-Emergent AEs and SAEs (All Causalities and Treatment-related)
time frame: Day 1 up to Day 40 (35 days after the last dose of metformin)
description: AEs with all causalities were any untoward medical occurrences in a study subject administered a product or medical device which did not necessarily had causal relationship with the treatment or usage. An SAE was an AE resulting in any of the following endpoints or deemed significant for any other reason: death; life threatening (immediate risk of death); inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or considered to be an important medical event. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent are events between first dose of study drug and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
arm group label: Sequence 1
arm group type: Experimental
description: Patients in sequence 1 will received treatment A (metformin) in Period 1 then complete at least 4 days of washout and continue to period 2 where treatment B (PF-04965842 + metformin) will be administered.
arm group label: Sequence 2
arm group type: Experimental
description: Patients in Sequence 2 will start treatment B (PF-04965842 + metformin) then go through a washout period of at least 4 days and continue to Period 2 where treatment A (metformin) will be administered.
intervention type: Drug
intervention name: Metformin
description: Commercially available metformin (GLUCOPHAGE®) as 500 mg tablets.
arm group label: Sequence 1
arm group label: Sequence 2
other name: Glucophage
intervention type: Drug
intervention name: PF-04965842
description: PF 04965842 100 mg tablets
arm group label: Sequence 1
arm group label: Sequence 2
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Pfizer CT.gov Call Center
role: Study Director
affiliation: Pfizer
facility: 
country: Belgium
url: https://pmiform.com/clinical-trial-info-request?StudyID=B7451034
description: To obtain contact information for a study center near you, click here.
responsible party type: Sponsor
mesh term: Metformin
mesh term: Abrocitinib
sharing ipd: No
ipd description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 