<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/NCT02183636</url>
  </required_header>
  <id_info>
    <org_study_id>1264.1</org_study_id>
    <nct_id>NCT02183636</nct_id>
  </id_info>
  <brief_title>Relative Bioavailability of Two Fixed Dose Combination Tablets of Linagliptin/Pioglitazone Compared With Single Linagliptin and Pioglitazone Tablets Administered Together to Healthy Male and Female Subjects</brief_title>
  <official_title>Relative Bioavailability of Two Fixed Dose Combination Tablets of Linagliptin 5 mg/Pioglitazone 45 mg Compared With Single Linagliptin 5 mg and Pioglitazone 45 mg Tablets Administered Together to Healthy Male and Female Subjects (Open, Randomised, Single Dose, Three-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>
      Determination of the relative bioavailability of 2 different formulations of a 5 mg&#xD;
      linagliptin (BI 1356)/45 mg pioglitazone fixed dose combination (FDC) tablet, formulation C5&#xD;
      and formulation C8, compared with the mono-components linagliptin and pioglitazone&#xD;
      administered together&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2009</start_date>
  <primary_completion_date type="Actual">December 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>AUC0-72 (area under the concentration-time curve of linagliptin in plasma over the time interval from 0 to 72 h)</measure>
    <time_frame>1 hour prior drug administration and up to 120 h after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax (maximum measured concentration of linagliptin in plasma)</measure>
    <time_frame>1 hour prior drug administration and up to 120 h after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC0-infinity (area under the concentration-time curve of pioglitazone in plasma over the time interval from 0 extrapolated to infinity)</measure>
    <time_frame>1 hour prior drug administration and up to 72 h after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax (maximum measured concentration of pioglitazone in plasma)</measure>
    <time_frame>1 hour prior drug administration and up to 72 h after drug administration</time_frame>
  </primary_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>1 hour prior drug administration and up to 120 h after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-infinity (area under the concentration-time curve of linagliptin in plasma over the time interval from 0 extrapolated to infinity)</measure>
    <time_frame>1 hour prior drug administration and up to 120 h after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-72 (area under the concentration-time curve of pioglitazone in plasma over the time interval from 0 to 72 h)</measure>
    <time_frame>1 hour prior drug administration and up to 72 after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in vital signs (blood pressure (BP) and pulse rate (PR))</measure>
    <time_frame>21 to 1 day prior start of treatment, at study visits 2 to 4 (prior to treatment administration and 24 h following treatment administration), and 7 days after last treatment administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of adverse events (AEs)</measure>
    <time_frame>until 7 days after last treatment administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of tolerability by the investigator</measure>
    <time_frame>on day 6 of each treatment and 7 days after last treatment administration</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">39</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Treatment 1 (T1)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Linagliptin/pioglitazone, FDC formulation C5</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment 2 (T2)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Linagliptin/pioglitazone, FDC formulation C8</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Reference (R)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Linagliptin tablet and pioglitazone tablet (Actos®)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Linagliptin/pioglitazone, FDC formulation C5</intervention_name>
    <description>film coated tablet (5 mg/45 mg)</description>
    <arm_group_label>Treatment 1 (T1)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Linagliptin/pioglitazone, FDC formulation C8</intervention_name>
    <description>film coated tablet (5 mg/45 mg)</description>
    <arm_group_label>Treatment 2 (T2)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Linagliptin tablet</intervention_name>
    <description>5 mg</description>
    <arm_group_label>Reference (R)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>pioglitazone tablet (Actos®)</intervention_name>
    <description>45 mg</description>
    <arm_group_label>Reference (R)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male and female subjects according to the following criteria: based upon a&#xD;
             complete medical history, including physical examination, vital signs (BP, PR),&#xD;
             12-lead ECG, and clinical laboratory tests&#xD;
&#xD;
          -  Age ≥18 and ≤55 years&#xD;
&#xD;
          -  Body mass index (BMI) ≥18.5 and ≤29.9 kg/m2&#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), 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 with a long half-life (&gt;24 h) within at least 1 month or less than 10&#xD;
             halflives of the respective drug prior to administration or during the trial&#xD;
&#xD;
          -  Use of drugs which might reasonably influence the results of the trial or based on the&#xD;
             knowledge at the time of protocol preparation within 10 days prior to administration&#xD;
             or during the trial&#xD;
&#xD;
          -  Participation in another trial with an investigational drug within 2 months prior to&#xD;
             administration or during the trial&#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 (more than 30 g/day for males and 20 g/day for females)&#xD;
&#xD;
          -  Drug abuse&#xD;
&#xD;
          -  Blood donation (more than 100 mL within 4 weeks prior to administration or during the&#xD;
             trial)&#xD;
&#xD;
          -  Excessive physical activities (within 1 week prior to administration or during the&#xD;
             trial)&#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;
        For female subjects:&#xD;
&#xD;
          -  Pregnancy or a positive pregnancy test, planning to become pregnant during the study,&#xD;
             or within 1 month of study completion or lactation period&#xD;
&#xD;
          -  No adequate contraception during the study and until 1 month after study completion,&#xD;
             i.e. implants, injectables, combined oral contraceptives, intrauterine device, sexual&#xD;
             abstinence (for at least 1 month before enrolment), vasectomised partner (vasectomy&#xD;
             performed at least 1 year prior to enrolment), or surgical sterilisation (including&#xD;
             hysterectomy). Females who did not have a vasectomised partner, were not sexually&#xD;
             abstinent, or were not surgically sterile were asked to additionally use barrier&#xD;
             contraception methods (i.e. condom, diaphragm with spermicide)&#xD;
&#xD;
        For male subjects:&#xD;
&#xD;
          -  Male subjects who did not agree to minimise the risk of female partners becoming&#xD;
             pregnant from the first dosing day until the completion of the post study medical&#xD;
             examination. Acceptable methods of contraception included barrier contraception and a&#xD;
             medically accepted contraceptive method for the female partner (intra-uterine device&#xD;
             with spermicide, hormonal contraceptive for at least 2 months)&#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/1264/1264.1_U10-1804-01.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>Pioglitazone</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/NCT02183636
org study id: 1264.1
nct id: NCT02183636
lead sponsor: 
Determination of the relative bioavailability of 2 different formulations of a 5 mg
      linagliptin (BI 1356)/45 mg pioglitazone fixed dose combination (FDC) tablet, formulation C5
      and formulation C8, compared with the mono-components linagliptin and pioglitazone
      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: 1 hour prior drug administration and up to 120 h after drug administration
measure: Cmax (maximum measured concentration of linagliptin in plasma)
time frame: 1 hour prior drug administration and up to 120 h after drug administration
measure: AUC0-infinity (area under the concentration-time curve of pioglitazone in plasma over the time interval from 0 extrapolated to infinity)
time frame: 1 hour prior drug administration and up to 72 h after drug administration
measure: Cmax (maximum measured concentration of pioglitazone in plasma)
time frame: 1 hour prior drug administration and up to 72 h after drug administration
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: 1 hour prior drug administration and up to 120 h after drug administration
measure: AUC0-infinity (area under the concentration-time curve of linagliptin in plasma over the time interval from 0 extrapolated to infinity)
time frame: 1 hour prior drug administration and up to 120 h after drug administration
measure: AUC0-72 (area under the concentration-time curve of pioglitazone in plasma over the time interval from 0 to 72 h)
time frame: 1 hour prior drug administration and up to 72 after drug administration
measure: Changes from baseline in vital signs (blood pressure (BP) and pulse rate (PR))
time frame: 21 to 1 day prior start of treatment, at study visits 2 to 4 (prior to treatment administration and 24 h following treatment administration), and 7 days after last treatment administration
measure: Occurrence of adverse events (AEs)
time frame: until 7 days after last treatment administration
measure: Assessment of tolerability by the investigator
time frame: on day 6 of each treatment and 7 days after last treatment administration
arm group label: Treatment 1 (T1)
arm group type: Experimental
description: Linagliptin/pioglitazone, FDC formulation C5
arm group label: Treatment 2 (T2)
arm group type: Experimental
description: Linagliptin/pioglitazone, FDC formulation C8
arm group label: Reference (R)
arm group type: Active Comparator
description: Linagliptin tablet and pioglitazone tablet (Actos®)
intervention type: Drug
intervention name: Linagliptin/pioglitazone, FDC formulation C5
description: film coated tablet (5 mg/45 mg)
arm group label: Treatment 1 (T1)
intervention type: Drug
intervention name: Linagliptin/pioglitazone, FDC formulation C8
description: film coated tablet (5 mg/45 mg)
arm group label: Treatment 2 (T2)
intervention type: Drug
intervention name: Linagliptin tablet
description: 5 mg
arm group label: Reference (R)
intervention type: Drug
intervention name: pioglitazone tablet (Actos®)
description: 45 mg
arm group label: Reference (R)
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/1264/1264.1_U10-1804-01.pdf
description: Related Info
responsible party type: Sponsor
mesh term: Pioglitazone
mesh term: Linagliptin