<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/NCT02221388</url>
  </required_header>
  <id_info>
    <org_study_id>1268.56</org_study_id>
    <nct_id>NCT02221388</nct_id>
  </id_info>
  <brief_title>Relative Bioavailability of Different Formulations of BI 671800 in Healthy Male and Female Volunteers</brief_title>
  <official_title>Relative Bioavailability of Different Salt Forms and Formulations of Single Doses Either 50 or 200 mg BI 671800 in the Fasted or Fed State. An Open-label, Randomised, Phase I Study With a 3-period Crossover Followed by Two Treatment Periods in Fixed Sequence in Healthy Male and Female Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      To compare the oral bioavailability and rate of absorption of two different formulations of&#xD;
      BI 671800 HEA (choline salt) tablets 200 mg, one with enteric coating (EC) and one without&#xD;
      EC, versus 2 x 100 mg BI 671800 ED (ethylenediamine salt) capsules. Both BI 671800 HEA&#xD;
      formulations were further investigated concerning food effect and one of the two BI 671800&#xD;
      HEA formulations identified by interim pharmacokinetic analysis was further investigated&#xD;
      concerning dose proportionality with 50 mg.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>February 2010</start_date>
  <primary_completion_date type="Actual">July 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>Cmax (maximum measured concentration of BI 671800 in plasma)</measure>
    <time_frame>Up to 24 hours after last drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC0-∞ (area under the concentration time curve of BI 671800 in plasma over the time interval from 0 extrapolated to infinity)</measure>
    <time_frame>Up to 24 hours after last drug administration</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>tmax (time from dosing to the maximum concentration of BI 671800 in plasma)</measure>
    <time_frame>Up to 24 hours after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-tz (area under the concentration-time curve of BI 671800 in plasma over the time interval from 0 to the time of the last quantifiable data point)</measure>
    <time_frame>Up to 24 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>λz (terminal rate constant in plasma)</measure>
    <time_frame>Up to 24 hours after drug adminnistration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t½ (terminal half-life of BI 671800 in plasma)</measure>
    <time_frame>Up to 24 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRTpo (mean residence time of BI 671800 in the body after po administration)</measure>
    <time_frame>Up to 24 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL/F (apparent clearance of BI 671800 in the plasma after extravascular administration)</measure>
    <time_frame>Up to 24 hours 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 24 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinical significant findings in physical examinations</measure>
    <time_frame>Up to 10 days after last drug admininstration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinical significant findings in vital signs</measure>
    <time_frame>Up to 10 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinical significant findings in ECG</measure>
    <time_frame>Up to 10 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinical significant findings in laboratory tests</measure>
    <time_frame>Up to 10 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>Up to 10 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Investigator assessed tolerability on a 4 point scale</measure>
    <time_frame>Up to 10 days after last drug administration</time_frame>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>BI 671800 ED capsules</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>BI 671800 HEA tablet in fasted state</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>BI 671800 HEA EC tablet in fasted state</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>BI 671800 HEA tablet in fed state</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>BI 671800 HEA EC tablet in fed state</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>BI 671800 HEA, 50 mg tablet in fasted state</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 671800 HEA, 200 mg tablets</intervention_name>
    <arm_group_label>BI 671800 HEA tablet in fasted state</arm_group_label>
    <arm_group_label>BI 671800 HEA tablet in fed state</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 671800 HEA EC, 200 mg tablets</intervention_name>
    <arm_group_label>BI 671800 HEA EC tablet in fasted state</arm_group_label>
    <arm_group_label>BI 671800 HEA EC tablet in fed state</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 671800 HEA, 50 mg tablets</intervention_name>
    <arm_group_label>BI 671800 HEA, 50 mg tablet in fasted state</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 671800 ED, 100 mg capsules</intervention_name>
    <arm_group_label>BI 671800 ED capsules</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard meal</intervention_name>
    <arm_group_label>BI 671800 HEA EC tablet in fed state</arm_group_label>
    <arm_group_label>BI 671800 HEA tablet in fed state</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy males and females according to the following criteria: Based upon a complete&#xD;
             medical history, including physical examination, vital signs (BP, PR), 12-lead ECG,&#xD;
             clinical laboratory tests&#xD;
&#xD;
          -  Age 21 to 50 years (incl.)&#xD;
&#xD;
          -  BMI 18.5 to 29.9 kg/m2 (incl.)&#xD;
&#xD;
          -  Signed and dated written informed consent prior to admission to the study in&#xD;
             accordance with GCP and the local legislation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any finding of the medical examination (including BP, PR and ECG) deviating from&#xD;
             normal and of clinical relevance&#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 or 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&#xD;
&#xD;
          -  Participation in another trial with an investigational drug within 2 months prior to&#xD;
             administration or during the trial&#xD;
&#xD;
          -  Smoker (more than 10 cigarettes or 3 cigars or 3 pipes daily)&#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 day 1 of visit 2)&#xD;
&#xD;
          -  Any laboratory value outside the reference range that is of clinical relevance,&#xD;
             especially repeated alanine aminotransferase (ALT), aspartate aminotransferase (AST),&#xD;
             gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP) or total bilirubin above&#xD;
             upper limit of normal (ULN) at screening and not resolved before dosing.&#xD;
&#xD;
          -  Inability to comply with dietary regimen of trial site&#xD;
&#xD;
          -  Unwilling to avoid excessive sunlight exposure&#xD;
&#xD;
          -  Use of drugs which might reasonably influence the results of the trial or that prolong&#xD;
             the QT/QTc interval within 10 days prior to administration or during the trial, and&#xD;
             CYP2C8 substrates such as amiodarone, amodiaquine, paclitaxel, rosiglitazone,&#xD;
             pioglitazone and repaglinide or CYP2C9 such as warfarin, tolbutamide, phenytoin,&#xD;
             losartan, acenocoumarol within 1 month or six half lives (whichever is greater).&#xD;
&#xD;
          -  A marked baseline prolongation of the 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 (e.g., heart failure,&#xD;
             hypokalaemia, family history of Long QT Syndrome)&#xD;
&#xD;
        For female subjects of childbearing potential only:&#xD;
&#xD;
          -  Positive pregnancy test, pregnancy or planning to become pregnant during the study or&#xD;
             within 2 months after study completion&#xD;
&#xD;
          -  No adequate contraception during the study including three months before first dosing&#xD;
             until 2 month after study completion, e.g. not any of the following: implants,&#xD;
             injectables, combined hormonal contraceptives, intrauterine device, or surgical&#xD;
             sterilisation (including hysterectomy). In addition to this, also a barrier method&#xD;
             (e.g. condom) will be required, if the female is not surgically sterilised.&#xD;
&#xD;
          -  Lactation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>50 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>
  <!-- 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/NCT02221388
org study id: 1268.56
nct id: NCT02221388
lead sponsor: 
To compare the oral bioavailability and rate of absorption of two different formulations of
      BI 671800 HEA (choline salt) tablets 200 mg, one with enteric coating (EC) and one without
      EC, versus 2 x 100 mg BI 671800 ED (ethylenediamine salt) capsules. Both BI 671800 HEA
      formulations were further investigated concerning food effect and one of the two BI 671800
      HEA formulations identified by interim pharmacokinetic analysis was further investigated
      concerning dose proportionality with 50 mg.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Cmax (maximum measured concentration of BI 671800 in plasma)
time frame: Up to 24 hours after last drug administration
measure: AUC0-∞ (area under the concentration time curve of BI 671800 in plasma over the time interval from 0 extrapolated to infinity)
time frame: Up to 24 hours after last drug administration
measure: tmax (time from dosing to the maximum concentration of BI 671800 in plasma)
time frame: Up to 24 hours after last drug administration
measure: AUC0-tz (area under the concentration-time curve of BI 671800 in plasma over the time interval from 0 to the time of the last quantifiable data point)
time frame: Up to 24 hours after drug administration
measure: λz (terminal rate constant in plasma)
time frame: Up to 24 hours after drug adminnistration
measure: t½ (terminal half-life of BI 671800 in plasma)
time frame: Up to 24 hours after drug administration
measure: MRTpo (mean residence time of BI 671800 in the body after po administration)
time frame: Up to 24 hours after drug administration
measure: CL/F (apparent clearance of BI 671800 in the plasma after extravascular administration)
time frame: Up to 24 hours after drug administration
measure: Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)
time frame: Up to 24 hours after drug administration
measure: Number of patients with clinical significant findings in physical examinations
time frame: Up to 10 days after last drug admininstration
measure: Number of patients with clinical significant findings in vital signs
time frame: Up to 10 days after last drug administration
measure: Number of patients with clinical significant findings in ECG
time frame: Up to 10 days after last drug administration
measure: Number of patients with clinical significant findings in laboratory tests
time frame: Up to 10 days after last drug administration
measure: Number of patients with adverse events
time frame: Up to 10 days after last drug administration
measure: Investigator assessed tolerability on a 4 point scale
time frame: Up to 10 days after last drug administration
arm group label: BI 671800 ED capsules
arm group type: Active Comparator
arm group label: BI 671800 HEA tablet in fasted state
arm group type: Experimental
arm group label: BI 671800 HEA EC tablet in fasted state
arm group type: Experimental
arm group label: BI 671800 HEA tablet in fed state
arm group type: Experimental
arm group label: BI 671800 HEA EC tablet in fed state
arm group type: Experimental
arm group label: BI 671800 HEA, 50 mg tablet in fasted state
arm group type: Experimental
intervention type: Drug
intervention name: BI 671800 HEA, 200 mg tablets
arm group label: BI 671800 HEA tablet in fasted state
arm group label: BI 671800 HEA tablet in fed state
intervention type: Drug
intervention name: BI 671800 HEA EC, 200 mg tablets
arm group label: BI 671800 HEA EC tablet in fasted state
arm group label: BI 671800 HEA EC tablet in fed state
intervention type: Drug
intervention name: BI 671800 HEA, 50 mg tablets
arm group label: BI 671800 HEA, 50 mg tablet in fasted state
intervention type: Drug
intervention name: BI 671800 ED, 100 mg capsules
arm group label: BI 671800 ED capsules
intervention type: Other
intervention name: Standard meal
arm group label: BI 671800 HEA EC tablet in fed state
arm group label: BI 671800 HEA tablet in fed state
criteria: 
gender: All
minimum age: 21 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor