<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/NCT02183415</url>
  </required_header>
  <id_info>
    <org_study_id>1218.3</org_study_id>
    <nct_id>NCT02183415</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BI 1356 BS as Tablet in Patients With Type 2 Diabetes</brief_title>
  <official_title>Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Oral Doses (2.5, 5, and 10 mg q.d. for 28 Days) of BI 1356 BS as Tablet in Patients With Type 2 Diabetes (Randomised, Double-blind, Placebo-controlled Within the Dose Groups)</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 investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of BI&#xD;
      1356 BS during 4 week treatment duration&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2005</start_date>
  <primary_completion_date type="Actual">January 2006</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Assessment of tolerability by investigator on a 4-point scale</measure>
    <time_frame>Day 50</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of adverse events</measure>
    <time_frame>up to 50 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with abnormal changes in clinical laboratory parameters</measure>
    <time_frame>Baseline, up to day 50</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cmax (maximum concentration of the analyte in plasma)</measure>
    <time_frame>before and up to 43 days after first study drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tmax (time from dosing to maximum concentration)</measure>
    <time_frame>before and up to 43 days after first study drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC (area under the concentration-time curve of the analyte in plasma) for several time points</measure>
    <time_frame>before and up to 43 days after first study drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax,ss (maximum concentration of the analyte in plasma at steady state over a uniform dosing interval)</measure>
    <time_frame>before and 0:30 h, 1 h, 1:30 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 hours after last study drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmin,ss (minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval)</measure>
    <time_frame>before and 0:30 h, 1 h, 1:30 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 hours after last study drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cpre,N (predose concentration of the analyte in plasma at steady state immediately before administration of the next dose N)</measure>
    <time_frame>pre-dose on day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tmax,ss (time from dosing to maximum concentration at steady state)</measure>
    <time_frame>before and 0:30 h, 1 h, 1:30 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 hours after last study drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUCτ,ss (area under the concentration time curve of the analyte in plasma at steady state over a uniform dosing interval)</measure>
    <time_frame>before and 0:30 h, 1 h, 1:30 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 hours after last study drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>λz,ss (terminal rate constant in plasma at steady state)</measure>
    <time_frame>before and 0:30 h, 1 h, 1:30 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 hours after last study drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2,ss (terminal half-life of the analyte in plasma at steady state)</measure>
    <time_frame>before and 0:30 h, 1 h, 1:30 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 hours after last study drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRTpo,ss (mean residence time of the analyte in the body after 12 administrations at steady state)</measure>
    <time_frame>before and 0:30 h, 1 h, 1:30 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 hours after last study drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL/F,ss (apparent clearance of the analyte in the plasma after extravascular administration at steady state)</measure>
    <time_frame>before and 0:30 h, 1 h, 1:30 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 hours after last study drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vz/F,ss (apparent volume of distribution during the terminal phase λz following an extravascular dose at steady state)</measure>
    <time_frame>before and 0:30 h, 1 h, 1:30 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 hours after last study drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PTF (peak trough fluctuation)</measure>
    <time_frame>before and 0:30 h, 1 h, 1:30 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 hours after last study drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation ratio (RA) based on Cmax</measure>
    <time_frame>up to 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>RA,AUC based on AUCτ</measure>
    <time_frame>up to 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dipeptidyl-Peptidase IV (DPP-IV) activity for several time points</measure>
    <time_frame>up to day 43</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in fasting plasma glucose (AUEC0-3) after MTT (meal tolerance test )</measure>
    <time_frame>days -1, 1 and 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma glucose levels</measure>
    <time_frame>up to day 43</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">77</enrollment>
  <condition>Diabetes Mellitus, Type 2</condition>
  <arm_group>
    <arm_group_label>BI 1356 BS, low dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>BI 1356 BS, medium dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>BI 1356 BS, high dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 1356 BS, low dose</intervention_name>
    <arm_group_label>BI 1356 BS, low dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 1356 BS, medium dose</intervention_name>
    <arm_group_label>BI 1356 BS, medium dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 1356 BS, high dose</intervention_name>
    <arm_group_label>BI 1356 BS, high dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female postmenopausal patients with proven diagnose of type 2 diabetes&#xD;
             mellitus treated with diet and exercise only or with one (or two) oral hypoglycaemic&#xD;
             agents besides glitazones&#xD;
&#xD;
          -  Glycosylated haemoglobin A1 (HbA1c)&#xD;
&#xD;
               -  ≤ 8.5 % at screening for patients treated with diet and exercise and/or one oral&#xD;
                  hypoglycaemic agent or&#xD;
&#xD;
               -  ≤ 8.0 % at screening for patients treated with two oral hypoglycaemic agents&#xD;
&#xD;
          -  Male patients: Age ≥21 and Age ≤70 years&#xD;
&#xD;
          -  Female patients: Age ≥60 and Age ≤70 years&#xD;
&#xD;
          -  BMI ≥18.5 and BMI ≤35 kg/m2 (Body Mass Index)&#xD;
&#xD;
          -  Caucasian ethnicity&#xD;
&#xD;
          -  Signed and dated written informed consent prior to admission to the study in&#xD;
             accordance with Good Clinical Practice and the local legislation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any finding of the medical examination (including Blood Pressure, Pulse Rate and&#xD;
             Electrocardiogram) deviating from normal and of not acceptable clinical relevance&#xD;
&#xD;
          -  Clinically relevant concomitant diseases like renal insufficiency, cardiac&#xD;
             insufficiency NYHA (New York Heart Association) II-IV, known cardiovascular diseases&#xD;
             including hypertension &gt; 150/95mmHg, stroke and TIA (transient ischemic attack)&#xD;
&#xD;
          -  Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic,&#xD;
             immunological or hormonal disorders besides type 2 diabetes, hyperlipidaemia and&#xD;
             medically treated hypertension&#xD;
&#xD;
          -  Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or&#xD;
             relevant neurological disorders besides polyneuropathy&#xD;
&#xD;
          -  Chronic or relevant acute infections (e.g. HIV, Hepatitis)&#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 hours) within at least one month or less&#xD;
             than 10 half-lives of the respective drug prior to administration or during the trial&#xD;
             except allowed co-medication&#xD;
&#xD;
          -  Use of drugs which might reasonably influence the results of the trial 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 two 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 40 g/day = 5 units/day)&#xD;
&#xD;
          -  Drug abuse&#xD;
&#xD;
          -  Blood donation (more than 100 mL within four weeks prior to administration or during&#xD;
             the trial)&#xD;
&#xD;
          -  Excessive physical activities (within one week prior to administration or during the&#xD;
             trial)&#xD;
&#xD;
          -  Any laboratory value outside the reference range and the clinical relevance is not&#xD;
             acceptable (or the value is more than three times higher than the upper limit of the&#xD;
             normal range e.g. liver enzymes)&#xD;
&#xD;
          -  Change of drug dosing of allowed co-medication (anti-hypertensive agents, acetylic&#xD;
             salicylic acid and statins) within the last 3 months&#xD;
&#xD;
          -  Fasted blood glucose &gt; 240 mg/dl (=13.3 mmol/L) on two consecutive days during washout&#xD;
&#xD;
          -  Serum creatinine above upper limit of normal at screening&#xD;
&#xD;
        Male Patients:&#xD;
&#xD;
          -  Not willing to use adequate contraception (condom use plus another form of&#xD;
             contraception e.g. spermicide, oral contraceptive taken by female partner,&#xD;
             sterilisation, intrauterine device) during the whole study period from the time of the&#xD;
             first intake of study drug until one month after the last intake&#xD;
&#xD;
        Female patients:&#xD;
&#xD;
          -  Positive pregnancy test&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <link>
    <url>http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/1218/1218.3_U06-1822.pdf</url>
    <description>Related Info</description>
  </link>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>July 4, 2014</study_first_submitted>
  <study_first_submitted_qc>July 4, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 8, 2014</study_first_posted>
  <last_update_submitted>July 4, 2014</last_update_submitted>
  <last_update_submitted_qc>July 4, 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>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <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/NCT02183415
org study id: 1218.3
nct id: NCT02183415
lead sponsor: 
Study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of BI
      1356 BS during 4 week treatment duration
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: Assessment of tolerability by investigator on a 4-point scale
time frame: Day 50
measure: Incidence of adverse events
time frame: up to 50 days
measure: Number of patients with abnormal changes in clinical laboratory parameters
time frame: Baseline, up to day 50
measure: Cmax (maximum concentration of the analyte in plasma)
time frame: before and up to 43 days after first study drug administration
measure: tmax (time from dosing to maximum concentration)
time frame: before and up to 43 days after first study drug administration
measure: AUC (area under the concentration-time curve of the analyte in plasma) for several time points
time frame: before and up to 43 days after first study drug administration
measure: Cmax,ss (maximum concentration of the analyte in plasma at steady state over a uniform dosing interval)
time frame: before and 0:30 h, 1 h, 1:30 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 hours after last study drug administration
measure: Cmin,ss (minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval)
time frame: before and 0:30 h, 1 h, 1:30 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 hours after last study drug administration
measure: Cpre,N (predose concentration of the analyte in plasma at steady state immediately before administration of the next dose N)
time frame: pre-dose on day 28
measure: tmax,ss (time from dosing to maximum concentration at steady state)
time frame: before and 0:30 h, 1 h, 1:30 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 hours after last study drug administration
measure: AUCτ,ss (area under the concentration time curve of the analyte in plasma at steady state over a uniform dosing interval)
time frame: before and 0:30 h, 1 h, 1:30 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 hours after last study drug administration
measure: λz,ss (terminal rate constant in plasma at steady state)
time frame: before and 0:30 h, 1 h, 1:30 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 hours after last study drug administration
measure: t1/2,ss (terminal half-life of the analyte in plasma at steady state)
time frame: before and 0:30 h, 1 h, 1:30 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 hours after last study drug administration
measure: MRTpo,ss (mean residence time of the analyte in the body after 12 administrations at steady state)
time frame: before and 0:30 h, 1 h, 1:30 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 hours after last study drug administration
measure: CL/F,ss (apparent clearance of the analyte in the plasma after extravascular administration at steady state)
time frame: before and 0:30 h, 1 h, 1:30 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 hours after last study drug administration
measure: Vz/F,ss (apparent volume of distribution during the terminal phase λz following an extravascular dose at steady state)
time frame: before and 0:30 h, 1 h, 1:30 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 hours after last study drug administration
measure: PTF (peak trough fluctuation)
time frame: before and 0:30 h, 1 h, 1:30 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 hours after last study drug administration
measure: Accumulation ratio (RA) based on Cmax
time frame: up to 28 days
measure: RA,AUC based on AUCτ
time frame: up to 28 days
measure: Dipeptidyl-Peptidase IV (DPP-IV) activity for several time points
time frame: up to day 43
measure: Change in fasting plasma glucose (AUEC0-3) after MTT (meal tolerance test )
time frame: days -1, 1 and 29
measure: Plasma glucose levels
time frame: up to day 43
arm group label: BI 1356 BS, low dose
arm group type: Experimental
arm group label: BI 1356 BS, medium dose
arm group type: Experimental
arm group label: BI 1356 BS, high dose
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: BI 1356 BS, low dose
arm group label: BI 1356 BS, low dose
intervention type: Drug
intervention name: BI 1356 BS, medium dose
arm group label: BI 1356 BS, medium dose
intervention type: Drug
intervention name: BI 1356 BS, high dose
arm group label: BI 1356 BS, high dose
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 21 Years
maximum age: 70 Years
healthy volunteers: No
url: http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/1218/1218.3_U06-1822.pdf
description: Related Info
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Linagliptin