<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/NCT02221401</url>
  </required_header>
  <id_info>
    <org_study_id>1288.1</org_study_id>
    <nct_id>NCT02221401</nct_id>
  </id_info>
  <brief_title>Bioequivalence of a Linagliptin / Metformin Fixed-dose Combination (FDC) Tablet Compared With Single Linagliptin and Metformin Tablets Administered Together in Healthy Volunteers</brief_title>
  <official_title>Bioequivalence of a 2.5 mg Linagliptin / 1000 mg Metformin Fixed-dose Combination Tablet Compared With Single Linagliptin 2.5 mg and Metformin 1000 mg Tablets Administered Together in Healthy Male and Female Volunteers (an Open-label, Randomised, Single Dose, Two-way 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>
      Study to demonstrate bioequivalence of a 2.5 mg linagliptin/1000 mg metformin fixed-dose&#xD;
      combination (FDC) tablet compared with single tablets of linagliptin 2.5 mg and metformin&#xD;
      1000 mg administered together.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 2010</start_date>
  <primary_completion_date type="Actual">April 2010</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>AUC0-72 (area under the concentration-time curve of linagliptin in plasma over the time interval from 0 to 72 h)</measure>
    <time_frame>up to 72 hours</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax (maximum measured concentration of the analyte in plasma)</measure>
    <time_frame>up to 72 hours</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC0-∞ (area under the concentration-time curve of metformin in plasma over the time interval from 0 extrapolated to infinity)</measure>
    <time_frame>up to 72 hours</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>AUC0-∞ (area under the concentration-time curve of linagliptin in plasma over the time interval from 0 extrapolated to infinity)</measure>
    <time_frame>up to 72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point)</measure>
    <time_frame>up to 72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>%AUCtz-∞ (percentage of AUCtz-∞ obtained by extrapolation)</measure>
    <time_frame>up to 72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUCt1-t2 (area under the concentration-time curve of the analyte in plasma over the time interval t1 to t2)</measure>
    <time_frame>up to 72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tmax (time from dosing until maximum concentration of the analyte in plasma)</measure>
    <time_frame>up to 72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>λz (terminal elimination rate constant in plasma)</measure>
    <time_frame>up to 72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2 (terminal half-life of the analyte in plasma)</measure>
    <time_frame>up to 72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRTpo (mean residence time of the analyte in the body after peroral administration)</measure>
    <time_frame>up to 72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL/F (apparent clearance of the analyte in the plasma after extravascular administration)</measure>
    <time_frame>up to 72 hours</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 72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with clinically significant findings in vital signs</measure>
    <time_frame>up to 7 days after last drug administration</time_frame>
    <description>blood pressure, pulse rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with clinically significant findings in 12-lead electrocardiogram (ECG)</measure>
    <time_frame>up to 7 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with clinically significant findings in laboratory tests</measure>
    <time_frame>up to 7 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with adverse events</measure>
    <time_frame>up to 7 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of tolerability by investigator on a 4-point scale</measure>
    <time_frame>up to 7 days after last drug administration</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">96</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Treatment A (FDC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment B (single agents)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Linagliptin/Metformin FDC</intervention_name>
    <arm_group_label>Treatment A (FDC)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Linagliptin</intervention_name>
    <arm_group_label>Treatment B (single agents)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <arm_group_label>Treatment B (single agents)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy men and women according to the following criteria: based upon a complete&#xD;
             medical history, including physical examination, vital signs (Blood pressure (BP),&#xD;
             Pulse Rate (PR)), 12-lead ECG, clinical laboratory tests&#xD;
&#xD;
          2. Age 18 to 55 years (inclusive)&#xD;
&#xD;
          3. Body mass index (BMI) of 18.5 to 29.9 kg/m2 (inclusive)&#xD;
&#xD;
          4. Signed and dated written informed consent prior to admission to the study in&#xD;
             accordance with Good Clinical Practice (GCP) and local legislation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any finding of the medical examination (including BP, PR and ECG) deviating from&#xD;
             normal and of clinical relevance&#xD;
&#xD;
          2. Any evidence of a clinically relevant concomitant disease&#xD;
&#xD;
          3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic,&#xD;
             immunological or hormonal disorders&#xD;
&#xD;
          4. Surgery of the gastrointestinal tract (except appendectomy)&#xD;
&#xD;
          5. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or&#xD;
             neurological disorders&#xD;
&#xD;
          6. History of relevant orthostatic hypotension, fainting spells or blackouts&#xD;
&#xD;
          7. Chronic or relevant acute infections&#xD;
&#xD;
          8. History of relevant allergy or hypersensitivity (including allergy to drug or its&#xD;
             excipients)&#xD;
&#xD;
          9. Intake of drugs within 1 month or less than 10 half-lives of the respective drug prior&#xD;
             to first study drug administration&#xD;
&#xD;
         10. Participation in another trial with an investigational drug within 2 months prior to&#xD;
             administration or during the trial&#xD;
&#xD;
         11. Smoker (more than 10 cigarettes or 3 cigars or 3 pipes daily)&#xD;
&#xD;
         12. Alcohol abuse (average consumption of more than 20 g/day in women and 30 g/day in men)&#xD;
&#xD;
         13. Drug abuse&#xD;
&#xD;
         14. Blood donation (more than 100 mL within 4 weeks before Day 1 of Visit 2)&#xD;
&#xD;
         15. Any laboratory value outside the reference range of clinical relevance&#xD;
&#xD;
         16. Inability to comply with dietary regimen of trial site&#xD;
&#xD;
             For female subjects of childbearing potential only:&#xD;
&#xD;
         17. Positive pregnancy test, pregnancy or planning to become pregnant during the study or&#xD;
             within 2 months after study completion&#xD;
&#xD;
         18. No adequate contraception during the study and until 1 month after study completion,&#xD;
             e.g. not any of the following: implants, injectables, combined hormonal&#xD;
             contraceptives, hormonal intrauterine device, sexual abstinence for at least 1 month&#xD;
             prior to first study drug administration, vasectomised partner (vasectomy performed at&#xD;
             least 1 year prior to enrolment), or surgical sterilization (including hysterectomy).&#xD;
             Women who did not have a vasectomised partner, were not sexually abstinent or&#xD;
             surgically sterile were asked to use an additional barrier method (e.g. condom).&#xD;
&#xD;
         19. 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</url>
    <description>Related Info</description>
  </link>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>August 19, 2014</study_first_submitted>
  <study_first_submitted_qc>August 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2014</study_first_posted>
  <last_update_submitted>August 19, 2014</last_update_submitted>
  <last_update_submitted_qc>August 19, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 20, 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>
    <mesh_term>Linagliptin</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/NCT02221401
org study id: 1288.1
nct id: NCT02221401
lead sponsor: 
Study to demonstrate bioequivalence of a 2.5 mg linagliptin/1000 mg metformin fixed-dose
      combination (FDC) tablet compared with single tablets of linagliptin 2.5 mg and metformin
      1000 mg administered together.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: AUC0-72 (area under the concentration-time curve of linagliptin in plasma over the time interval from 0 to 72 h)
time frame: up to 72 hours
measure: Cmax (maximum measured concentration of the analyte in plasma)
time frame: up to 72 hours
measure: AUC0-∞ (area under the concentration-time curve of metformin in plasma over the time interval from 0 extrapolated to infinity)
time frame: up to 72 hours
measure: AUC0-∞ (area under the concentration-time curve of linagliptin in plasma over the time interval from 0 extrapolated to infinity)
time frame: up to 72 hours
measure: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point)
time frame: up to 72 hours
measure: %AUCtz-∞ (percentage of AUCtz-∞ obtained by extrapolation)
time frame: up to 72 hours
measure: AUCt1-t2 (area under the concentration-time curve of the analyte in plasma over the time interval t1 to t2)
time frame: up to 72 hours
measure: tmax (time from dosing until maximum concentration of the analyte in plasma)
time frame: up to 72 hours
measure: λz (terminal elimination rate constant in plasma)
time frame: up to 72 hours
measure: t1/2 (terminal half-life of the analyte in plasma)
time frame: up to 72 hours
measure: MRTpo (mean residence time of the analyte in the body after peroral administration)
time frame: up to 72 hours
measure: CL/F (apparent clearance of the analyte in the plasma after extravascular administration)
time frame: up to 72 hours
measure: Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)
time frame: up to 72 hours
measure: Number of subjects with clinically significant findings in vital signs
time frame: up to 7 days after last drug administration
description: blood pressure, pulse rate
measure: Number of subjects with clinically significant findings in 12-lead electrocardiogram (ECG)
time frame: up to 7 days after last drug administration
measure: Number of subjects with clinically significant findings in laboratory tests
time frame: up to 7 days after last drug administration
measure: Number of subjects with adverse events
time frame: up to 7 days after last drug administration
measure: Assessment of tolerability by investigator on a 4-point scale
time frame: up to 7 days after last drug administration
arm group label: Treatment A (FDC)
arm group type: Experimental
arm group label: Treatment B (single agents)
arm group type: Active Comparator
intervention type: Drug
intervention name: Linagliptin/Metformin FDC
arm group label: Treatment A (FDC)
intervention type: Drug
intervention name: Linagliptin
arm group label: Treatment B (single agents)
intervention type: Drug
intervention name: Metformin
arm group label: Treatment B (single agents)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor
mesh term: Metformin
mesh term: Linagliptin