<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/NCT02183571</url>
  </required_header>
  <id_info>
    <org_study_id>1218.57</org_study_id>
    <nct_id>NCT02183571</nct_id>
  </id_info>
  <brief_title>Bioequivalence Study of Two Strengths of Two Different Metformin Tablets Administered to Healthy Male and Female Subjects</brief_title>
  <official_title>Bioequivalence of Two Strengths (1000 mg and 500 mg) of Two Different Metformin Tablets Administered to Healthy Male and Female Subjects in an Open, Randomised, Single-dose, Two-period Crossover, Phase I Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      Investigation of bioequivalence of BMS Glucophage® tablets and Merck Glucophage® tablets in&#xD;
      the strengths of 1000 mg (part I) and 500 mg (part II)&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>February 2009</start_date>
  <primary_completion_date type="Actual">April 2009</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>AUC0-infinity (area under the concentration-time curve of metformin in plasma over the time interval from 0 extrapolated to infinity)</measure>
    <time_frame>up to 48 h after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax (maximum measured concentration of metformin in plasma)</measure>
    <time_frame>up to 48 hours after drug administration</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>AUC0-tz (area under the concentration-time curve of metformin in plasma over the time interval from 0 to the time of the last quantifiable data point)</measure>
    <time_frame>up to 48 h after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUCt1-t2 (Area under the concentration time curve of metformin in plasma over the time interval t1 to t2)</measure>
    <time_frame>up to 48 h after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tmax (time from dosing to the maximum concentration of metformin in plasma)</measure>
    <time_frame>up to 48 h after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>λz (terminal rate constant in plasma)</measure>
    <time_frame>up to 48 h after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2 (terminal half-life of metformin in plasma)</measure>
    <time_frame>up to 48 h after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRTpo (mean residence time of metformin in the body after po administration)</measure>
    <time_frame>up to 48 h after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL/F (apparent clearance of metformin in the plasma after extravascular administration)</measure>
    <time_frame>up to 48 h after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)</measure>
    <time_frame>up to 48 h after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically relevant differences in physical examination</measure>
    <time_frame>Baseline, day 1 prior, within 2-10 days following the last study drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically relevant differences in vital signs (BP (Blood pressure), PR (Pulse rate))</measure>
    <time_frame>Baseline, day 1 prior, within 2-10 days following the last study drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically relevant differences in 12-lead ECG (electrocardiogram)</measure>
    <time_frame>Baseline, day 1 prior, within 2-10 days following the last study drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically relevant differences in clinical laboratory tests</measure>
    <time_frame>Baseline, day 1 prior, within 2-10 days following the last study drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>within 2- 10 after last study drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of tolerability by investigator on a 4 point scale</measure>
    <time_frame>within 2- 10 after last study drug administration</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">56</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Glucophage® high dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part I: Treatment A + B</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Glucophage® low dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part II: Treatment C+ D</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Merck Glucophage® high dose</intervention_name>
    <description>Part I: Treatment A</description>
    <arm_group_label>Glucophage® high dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BMS Glucophage® high dose</intervention_name>
    <description>Part I: Treatment B</description>
    <arm_group_label>Glucophage® high dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Merck Glucophage® low dose</intervention_name>
    <description>Part II: Treatment C</description>
    <arm_group_label>Glucophage® low dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BMS Glucophage® low dose</intervention_name>
    <description>Part II: Treatment D</description>
    <arm_group_label>Glucophage® low dose</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy males and females according to the following criteria: a complete medical&#xD;
             history, including the physical examination, vital signs (Blood Pressure (BP), Pulse&#xD;
             Rate (PR)), 12-lead electrocardiogram (ECG) and clinical laboratory tests&#xD;
&#xD;
          -  Age ≥ 18 and Age ≤ 55 years&#xD;
&#xD;
          -  BMI ≥ 18.5 and ≤ 29.9 kg/m2 (Body Mass Index)&#xD;
&#xD;
          -  Signed and dated written informed consent prior to admission to the study in&#xD;
             accordance with Good clinical practice (GCP) and the local legislation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any finding of the medical examination deviating from normal and of clinical&#xD;
             relevance. Repeated measurement of a systolic blood pressure greater than 140 mm Hg or&#xD;
             diastolic blood pressure greater than 90 mm Hg&#xD;
&#xD;
          -  Any evidence of a clinically relevant concomitant disease&#xD;
&#xD;
          -  Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic,&#xD;
             immunological or hormonal disorders&#xD;
&#xD;
          -  Surgery of the gastrointestinal tract (except appendectomy)&#xD;
&#xD;
          -  Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or&#xD;
             neurological disorders&#xD;
&#xD;
          -  History of relevant orthostatic hypotension, fainting spells or blackouts&#xD;
&#xD;
          -  Chronic or relevant acute infections&#xD;
&#xD;
          -  History of relevant allergy/hypersensitivity (including allergy to drug or its&#xD;
             excipients)&#xD;
&#xD;
          -  Intake of drugs within one month or less than 10 half-lives of the respective drug&#xD;
             prior to first study drug administration except if a relevant interaction can be ruled&#xD;
             out&#xD;
&#xD;
          -  Participation in another trial with an investigational drug within two months prior to&#xD;
             first study drug administration&#xD;
&#xD;
          -  Smoker (&gt; 10 cigarettes or &gt; 3 cigars or &gt; 3 pipes/day)&#xD;
&#xD;
          -  Inability to refrain from smoking on trial days&#xD;
&#xD;
          -  Alcohol abuse (average consumption of more than 20 g/day in females and 30 g/day in&#xD;
             males)&#xD;
&#xD;
          -  Drug abuse&#xD;
&#xD;
          -  Blood donation (more than 100 mL within four weeks prior to the start of study)&#xD;
&#xD;
          -  Any laboratory value outside the reference range that is of clinical relevance&#xD;
&#xD;
          -  Inability to comply with dietary regimen of trial site&#xD;
&#xD;
          -  A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a&#xD;
             QTc interval &gt;450 ms)&#xD;
&#xD;
          -  A history of additional risk factors for Torsade de pointes (TdP) (e.g., heart&#xD;
             failure, hypokalemia, family history of Long QT Syndrome)&#xD;
&#xD;
        For female subjects:&#xD;
&#xD;
          -  Positive pregnancy test, pregnancy or planning to become pregnant during the study or&#xD;
             within 1 month after study completion&#xD;
&#xD;
          -  No adequate contraception during the study and until 1 month after study completion,&#xD;
             i.e. not any of the following: implants, injectables, combined oral contraceptives,&#xD;
             IUD (intrauterine device), sexual abstinence for at least 1 month prior to enrolment,&#xD;
             vasectomised partner (vasectomy performed at least 1 year prior to enrolment), or&#xD;
             surgical sterilisation (including hysterectomy). Females, who do not have a&#xD;
             vasectomised partner, are not sexually abstinent or surgically sterile will be asked&#xD;
             to use an additional barrier method (e.g. condom, diaphragm with spermicide)&#xD;
&#xD;
          -  Lactation&#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>
  <link>
    <url>http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/1218/1218.57_U09-2155-01.pdf</url>
    <description>Related Info</description>
  </link>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>July 7, 2014</study_first_submitted>
  <study_first_submitted_qc>July 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 8, 2014</study_first_posted>
  <last_update_submitted>July 7, 2014</last_update_submitted>
  <last_update_submitted_qc>July 7, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 8, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</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/NCT02183571
org study id: 1218.57
nct id: NCT02183571
lead sponsor: 
Investigation of bioequivalence of BMS Glucophage® tablets and Merck Glucophage® tablets in
      the strengths of 1000 mg (part I) and 500 mg (part II)
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: AUC0-infinity (area under the concentration-time curve of metformin in plasma over the time interval from 0 extrapolated to infinity)
time frame: up to 48 h after drug administration
measure: Cmax (maximum measured concentration of metformin in plasma)
time frame: up to 48 hours after drug administration
measure: AUC0-tz (area under the concentration-time curve of metformin in plasma over the time interval from 0 to the time of the last quantifiable data point)
time frame: up to 48 h after drug administration
measure: AUCt1-t2 (Area under the concentration time curve of metformin in plasma over the time interval t1 to t2)
time frame: up to 48 h after drug administration
measure: tmax (time from dosing to the maximum concentration of metformin in plasma)
time frame: up to 48 h after drug administration
measure: λz (terminal rate constant in plasma)
time frame: up to 48 h after drug administration
measure: t1/2 (terminal half-life of metformin in plasma)
time frame: up to 48 h after drug administration
measure: MRTpo (mean residence time of metformin in the body after po administration)
time frame: up to 48 h after drug administration
measure: CL/F (apparent clearance of metformin in the plasma after extravascular administration)
time frame: up to 48 h after drug administration
measure: Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)
time frame: up to 48 h after drug administration
measure: Number of patients with clinically relevant differences in physical examination
time frame: Baseline, day 1 prior, within 2-10 days following the last study drug administration
measure: Number of patients with clinically relevant differences in vital signs (BP (Blood pressure), PR (Pulse rate))
time frame: Baseline, day 1 prior, within 2-10 days following the last study drug administration
measure: Number of patients with clinically relevant differences in 12-lead ECG (electrocardiogram)
time frame: Baseline, day 1 prior, within 2-10 days following the last study drug administration
measure: Number of patients with clinically relevant differences in clinical laboratory tests
time frame: Baseline, day 1 prior, within 2-10 days following the last study drug administration
measure: Number of patients with adverse events
time frame: within 2- 10 after last study drug administration
measure: Assessment of tolerability by investigator on a 4 point scale
time frame: within 2- 10 after last study drug administration
arm group label: Glucophage® high dose
arm group type: Experimental
description: Part I: Treatment A + B
arm group label: Glucophage® low dose
arm group type: Experimental
description: Part II: Treatment C+ D
intervention type: Drug
intervention name: Merck Glucophage® high dose
description: Part I: Treatment A
arm group label: Glucophage® high dose
intervention type: Drug
intervention name: BMS Glucophage® high dose
description: Part I: Treatment B
arm group label: Glucophage® high dose
intervention type: Drug
intervention name: Merck Glucophage® low dose
description: Part II: Treatment C
arm group label: Glucophage® low dose
intervention type: Drug
intervention name: BMS Glucophage® low dose
description: Part II: Treatment D
arm group label: Glucophage® low dose
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
url: http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/1218/1218.57_U09-2155-01.pdf
description: Related Info
responsible party type: Sponsor
mesh term: Metformin