<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/NCT02221180</url>
  </required_header>
  <id_info>
    <org_study_id>CR104980</org_study_id>
    <secondary_id>28431754DIA1071</secondary_id>
    <nct_id>NCT02221180</nct_id>
  </id_info>
  <brief_title>Bioequivalence Study of Metformin Component of Fixed Dose Combination (FDC) Immediate Release (IR) Tablet of Canagliflozin and Metformin Compared to Metformin IR Tablet Co-administered With Canagliflozin in Healthy Fed and Fasted Participants</brief_title>
  <official_title>A Single-Dose, Open-Label, Randomized, 4-Way Crossover Pivotal Study to Assess the Bioequivalence of the Metformin Component of the Fixed Dose Combination Tablet of Canagliflozin and Metformin Immediate Release (IR) 1 x (150 mg/500 mg) With Respect to the Metformin IR Tablet (Locally Sourced From Canada [Glucophage, 1 x 500 mg]) Coadministered With Canagliflozin (1 x 50 mg and 1 x 100 mg) in Healthy Fed and Fasted Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Janssen Research &amp; Development, LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Janssen Research &amp; Development, LLC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the bioequivalence of metformin component of the&#xD;
      canagliflozin and metformin immediate release (IR) fixed dose combination (FDC) tablet&#xD;
      compared with the metformin IR tablet co-administered with canagliflozin in healthy fed and&#xD;
      fasted participants.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized (study medication assigned to participants by chance), open-label&#xD;
      (identity of study drug will be known to volunteer and study staff), single-center,&#xD;
      single-dose, 4-treatment, 4-way crossover (method used to switch participants from one study&#xD;
      group to another in a clinical trial, like the flip of a coin) study in healthy adult&#xD;
      participants. The study will have 3 phases: Screening Phase (approximately 3 weeks, Day -22&#xD;
      to Day -2), Open-Label Treatment Phase (consisting of 4 single-dose treatment periods of 3&#xD;
      days each [Day -1 to Day 2], each separated by a washout period of 7 days) and Follow-up&#xD;
      Phase (5 to 7 days after last study-related procedure on Day 2 of treatment period 4). All&#xD;
      the eligible participants will be randomly assigned to 1 of 4 treatment sequences and will&#xD;
      receive 2 treatments under fasting and 2 treatments under fed conditions. Blood samples will&#xD;
      be collected for evaluation of pharmacokinetics (how the drug is absorbed in the body,&#xD;
      distributed within the body, and how it is removed from the body over time) at pre-dose and&#xD;
      post-dose of study treatment. Participants' safety will be monitored throughout the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">November 2014</completion_date>
  <primary_completion_date type="Actual">November 2014</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Plasma Concentration of Metformin</measure>
    <time_frame>Pre-dose, up to 24 hours afterdose</time_frame>
    <description>Plasma concentrations of metformin are used to evaluate how much metformin is in the blood over time.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma Concentration of Canagliflozin</measure>
    <time_frame>2 hours after dosing</time_frame>
    <description>Plasma concentrations of canagliflozin are used to evaluate how much canagliflozin is in the blood, 2 hours after dosing.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse Events</measure>
    <time_frame>Up to approximately 58 days</time_frame>
    <description>The number and type of adverse events will be reported from Day 1 of treatment period 1 through 5-7 days after treatment period 4 including a 7+/- 1 day washout period between treatment periods (total time is approximately 58 days).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Laboratory Test</measure>
    <time_frame>Up to approximately 58 days</time_frame>
    <description>Clinically relevant changes occurring in laboratory safety parameters will be evaluated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vital Signs</measure>
    <time_frame>Up to approximately 58 days</time_frame>
    <description>Blood pressure, pulse, and oral body temperature will be evaluated.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">2</enrollment>
  <condition>Bioequivalence</condition>
  <arm_group>
    <arm_group_label>Treatment Sequence ABDC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment A (1 immediate release (IR) fixed dose combination [FDC] tablet containing canagliflozin 150 milligram [mg] and metformin 500 mg orally under fed condition) on Day 1 of treatment period 1, followed by Treatment B (1 canagliflozin tablet 50 mg and 1 canagliflozin tablet 100 mg along with 1 IR tablet of metformin 500 mg orally under fed condition) on Day 1 of treatment period 2, followed by Treatment D (1 canagliflozin tablet 50 mg and 1 canagliflozin tablet 100 mg along with 1 IR tablet of metformin 500 mg orally under fasted condition) on Day 1 of treatment period 3, then Treatment C (1 IR FDC tablet containing canagliflozin 150 mg and metformin 500 mg orally under fasted condition) on Day 1 of treatment period 4. A washout period of 7 days will be maintained between each treatment period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment Sequence BCAD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment B (1 canagliflozin tablet 50 mg and 1 canagliflozin tablet 100 mg along with 1 IR tablet of metformin 500 mg orally under fed condition) on Day 1 of treatment period 1, followed by Treatment C (1 IR FDC tablet containing canagliflozin 150 mg and metformin 500 mg orally under fasted condition) on Day 1 of treatment period 2, followed by Treatment A (1 IR FDC tablet containing canagliflozin 150 mg and metformin 500 mg orally under fed condition) on Day 1 of treatment period 3, then Treatment D (1 canagliflozin tablet 50 mg and 1 canagliflozin tablet 100 mg along with 1 IR tablet of metformin 500 mg orally under fasted condition) on Day 1 of treatment period 4. A washout period of 7 days will be maintained between each treatment period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment Sequence CDBA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment C (1 IR FDC tablet containing canagliflozin 150 mg and metformin 500 mg orally under fasted condition) on Day 1 of treatment period 1, followed by Treatment D (1 canagliflozin tablet 50 mg and 1 canagliflozin tablet 100 mg along with 1 IR tablet of metformin 500 mg orally under fasted condition) on Day 1 of treatment period 2, followed by Treatment B (1 canagliflozin tablet 50 mg and 1 canagliflozin tablet 100 mg along with 1 IR tablet of metformin 500 mg orally under fed condition) on Day 1 of treatment period 3, then Treatment A (1 IR FDC tablet containing canagliflozin 150 mg and metformin 500 mg orally under fed condition) on Day 1 of treatment period 4. A washout period of 7 days will be maintained between each treatment period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment Sequence DACB</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment D (1 canagliflozin tablet 50 mg and 1 canagliflozin tablet 100 mg along with 1 IR tablet of metformin 500 mg orally under fasted condition) on Day 1 of treatment period 1, followed by Treatment A (1 IR FDC tablet containing canagliflozin 150 mg and metformin 500 mg orally under fed condition) on Day 1 of treatment period 2, followed by Treatment C (1 IR FDC tablet containing canagliflozin 150 mg and metformin 500 mg orally under fasted condition) on Day 1 of treatment period 3, then Treatment B (1 canagliflozin tablet 50 mg and 1 canagliflozin tablet 100 mg along with 1 IR tablet of metformin 500 mg orally under fed condition) on Day 1 of treatment period 4. A washout period of 7 days will be maintained between each treatment period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Canagliflozin and Metformin Immediate Release (IR) Fixed Dose Combination [FDC]</intervention_name>
    <description>Participants will receive 1 IR FDC tablet containing canagliflozin 150 mg and metformin 500 mg orally under fed or fasted condition in each treatment period as per treatment sequence.</description>
    <arm_group_label>Treatment Sequence ABDC</arm_group_label>
    <arm_group_label>Treatment Sequence BCAD</arm_group_label>
    <arm_group_label>Treatment Sequence CDBA</arm_group_label>
    <arm_group_label>Treatment Sequence DACB</arm_group_label>
    <other_name>CANA/MET IR FDC</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Canagliflozin</intervention_name>
    <description>Participants will receive canagliflozin 150 mg (50 mg+100 mg oral tablet) under fed or fasted condition in each treatment period as per treatment sequence.</description>
    <arm_group_label>Treatment Sequence ABDC</arm_group_label>
    <arm_group_label>Treatment Sequence BCAD</arm_group_label>
    <arm_group_label>Treatment Sequence CDBA</arm_group_label>
    <arm_group_label>Treatment Sequence DACB</arm_group_label>
    <other_name>CANA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>Participants will receive metformin 500 mg tablet orally under fed or fasted condition in each treatment period as per treatment sequence.</description>
    <arm_group_label>Treatment Sequence ABDC</arm_group_label>
    <arm_group_label>Treatment Sequence BCAD</arm_group_label>
    <arm_group_label>Treatment Sequence CDBA</arm_group_label>
    <arm_group_label>Treatment Sequence DACB</arm_group_label>
    <other_name>MET</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Body mass index (BMI) between 18.5 and 30 kilogram per square meter (kg/m^2)&#xD;
             (inclusive) and a body weight of not less than 50 kg&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of or current medical illness, abnormal values for hematology or clinical&#xD;
             chemistry laboratory tests, or abnormal physical examination, vital signs or 12-lead&#xD;
             electrocardiogram (ECG) deemed to be clinically significant by the Investigator&#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>Janssen Research &amp; Development, LLC Clinical Trial</last_name>
    <role>Study Director</role>
    <affiliation>Janssen Research &amp; Development, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Lincoln</city>
        <state>Nebraska</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2014</verification_date>
  <study_first_submitted>August 18, 2014</study_first_submitted>
  <study_first_submitted_qc>August 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2014</study_first_posted>
  <last_update_submitted>November 24, 2014</last_update_submitted>
  <last_update_submitted_qc>November 24, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 25, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Bioequivalence</keyword>
  <keyword>Metformin</keyword>
  <keyword>Canagliflozin</keyword>
  <keyword>Healthy</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
    <mesh_term>Canagliflozin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02221180
org study id: CR104980
secondary id: 28431754DIA1071
nct id: NCT02221180
lead sponsor: 
has dmc: No
The purpose of this study is to evaluate the bioequivalence of metformin component of the
      canagliflozin and metformin immediate release (IR) fixed dose combination (FDC) tablet
      compared with the metformin IR tablet co-administered with canagliflozin in healthy fed and
      fasted participants.
This is a randomized (study medication assigned to participants by chance), open-label
      (identity of study drug will be known to volunteer and study staff), single-center,
      single-dose, 4-treatment, 4-way crossover (method used to switch participants from one study
      group to another in a clinical trial, like the flip of a coin) study in healthy adult
      participants. The study will have 3 phases: Screening Phase (approximately 3 weeks, Day -22
      to Day -2), Open-Label Treatment Phase (consisting of 4 single-dose treatment periods of 3
      days each [Day -1 to Day 2], each separated by a washout period of 7 days) and Follow-up
      Phase (5 to 7 days after last study-related procedure on Day 2 of treatment period 4). All
      the eligible participants will be randomly assigned to 1 of 4 treatment sequences and will
      receive 2 treatments under fasting and 2 treatments under fed conditions. Blood samples will
      be collected for evaluation of pharmacokinetics (how the drug is absorbed in the body,
      distributed within the body, and how it is removed from the body over time) at pre-dose and
      post-dose of study treatment. Participants' safety will be monitored throughout the study.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Plasma Concentration of Metformin
time frame: Pre-dose, up to 24 hours afterdose
description: Plasma concentrations of metformin are used to evaluate how much metformin is in the blood over time.
measure: Plasma Concentration of Canagliflozin
time frame: 2 hours after dosing
description: Plasma concentrations of canagliflozin are used to evaluate how much canagliflozin is in the blood, 2 hours after dosing.
measure: Adverse Events
time frame: Up to approximately 58 days
description: The number and type of adverse events will be reported from Day 1 of treatment period 1 through 5-7 days after treatment period 4 including a 7+/- 1 day washout period between treatment periods (total time is approximately 58 days).
measure: Clinical Laboratory Test
time frame: Up to approximately 58 days
description: Clinically relevant changes occurring in laboratory safety parameters will be evaluated.
measure: Vital Signs
time frame: Up to approximately 58 days
description: Blood pressure, pulse, and oral body temperature will be evaluated.
arm group label: Treatment Sequence ABDC
arm group type: Experimental
description: Treatment A (1 immediate release (IR) fixed dose combination [FDC] tablet containing canagliflozin 150 milligram [mg] and metformin 500 mg orally under fed condition) on Day 1 of treatment period 1, followed by Treatment B (1 canagliflozin tablet 50 mg and 1 canagliflozin tablet 100 mg along with 1 IR tablet of metformin 500 mg orally under fed condition) on Day 1 of treatment period 2, followed by Treatment D (1 canagliflozin tablet 50 mg and 1 canagliflozin tablet 100 mg along with 1 IR tablet of metformin 500 mg orally under fasted condition) on Day 1 of treatment period 3, then Treatment C (1 IR FDC tablet containing canagliflozin 150 mg and metformin 500 mg orally under fasted condition) on Day 1 of treatment period 4. A washout period of 7 days will be maintained between each treatment period.
arm group label: Treatment Sequence BCAD
arm group type: Experimental
description: Treatment B (1 canagliflozin tablet 50 mg and 1 canagliflozin tablet 100 mg along with 1 IR tablet of metformin 500 mg orally under fed condition) on Day 1 of treatment period 1, followed by Treatment C (1 IR FDC tablet containing canagliflozin 150 mg and metformin 500 mg orally under fasted condition) on Day 1 of treatment period 2, followed by Treatment A (1 IR FDC tablet containing canagliflozin 150 mg and metformin 500 mg orally under fed condition) on Day 1 of treatment period 3, then Treatment D (1 canagliflozin tablet 50 mg and 1 canagliflozin tablet 100 mg along with 1 IR tablet of metformin 500 mg orally under fasted condition) on Day 1 of treatment period 4. A washout period of 7 days will be maintained between each treatment period.
arm group label: Treatment Sequence CDBA
arm group type: Experimental
description: Treatment C (1 IR FDC tablet containing canagliflozin 150 mg and metformin 500 mg orally under fasted condition) on Day 1 of treatment period 1, followed by Treatment D (1 canagliflozin tablet 50 mg and 1 canagliflozin tablet 100 mg along with 1 IR tablet of metformin 500 mg orally under fasted condition) on Day 1 of treatment period 2, followed by Treatment B (1 canagliflozin tablet 50 mg and 1 canagliflozin tablet 100 mg along with 1 IR tablet of metformin 500 mg orally under fed condition) on Day 1 of treatment period 3, then Treatment A (1 IR FDC tablet containing canagliflozin 150 mg and metformin 500 mg orally under fed condition) on Day 1 of treatment period 4. A washout period of 7 days will be maintained between each treatment period.
arm group label: Treatment Sequence DACB
arm group type: Experimental
description: Treatment D (1 canagliflozin tablet 50 mg and 1 canagliflozin tablet 100 mg along with 1 IR tablet of metformin 500 mg orally under fasted condition) on Day 1 of treatment period 1, followed by Treatment A (1 IR FDC tablet containing canagliflozin 150 mg and metformin 500 mg orally under fed condition) on Day 1 of treatment period 2, followed by Treatment C (1 IR FDC tablet containing canagliflozin 150 mg and metformin 500 mg orally under fasted condition) on Day 1 of treatment period 3, then Treatment B (1 canagliflozin tablet 50 mg and 1 canagliflozin tablet 100 mg along with 1 IR tablet of metformin 500 mg orally under fed condition) on Day 1 of treatment period 4. A washout period of 7 days will be maintained between each treatment period.
intervention type: Drug
intervention name: Canagliflozin and Metformin Immediate Release (IR) Fixed Dose Combination [FDC]
description: Participants will receive 1 IR FDC tablet containing canagliflozin 150 mg and metformin 500 mg orally under fed or fasted condition in each treatment period as per treatment sequence.
arm group label: Treatment Sequence ABDC
arm group label: Treatment Sequence BCAD
arm group label: Treatment Sequence CDBA
arm group label: Treatment Sequence DACB
other name: CANA/MET IR FDC
intervention type: Drug
intervention name: Canagliflozin
description: Participants will receive canagliflozin 150 mg (50 mg+100 mg oral tablet) under fed or fasted condition in each treatment period as per treatment sequence.
arm group label: Treatment Sequence ABDC
arm group label: Treatment Sequence BCAD
arm group label: Treatment Sequence CDBA
arm group label: Treatment Sequence DACB
other name: CANA
intervention type: Drug
intervention name: Metformin
description: Participants will receive metformin 500 mg tablet orally under fed or fasted condition in each treatment period as per treatment sequence.
arm group label: Treatment Sequence ABDC
arm group label: Treatment Sequence BCAD
arm group label: Treatment Sequence CDBA
arm group label: Treatment Sequence DACB
other name: MET
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Janssen Research & Development, LLC Clinical Trial
role: Study Director
affiliation: Janssen Research & Development, LLC
facility: 
country: United States
responsible party type: Sponsor
mesh term: Metformin
mesh term: Canagliflozin