<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/NCT02183324</url>
  </required_header>
  <id_info>
    <org_study_id>1218.12</org_study_id>
    <nct_id>NCT02183324</nct_id>
  </id_info>
  <brief_title>BI 1356 BS in Japanese Patients With Type 2 Diabetes Mellitus</brief_title>
  <official_title>A Randomised, Double-blind, Placebo-controlled, Multiple Dose Phase II Study of BI 1356 BS (0.5 mg, 2.5 mg, and 10 mg in Tablet q.d. Administered Orally for 28 Days) to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics in Japanese Patients With Type 2 Diabetes Mellitus</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 evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of BI 1356&#xD;
      BS (0.5 mg, 2.5 mg, and 10 mg) administered orally once daily for 28 days in Japanese&#xD;
      patients with type 2 diabetes mellitus.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>February 2007</start_date>
  <primary_completion_date type="Actual">June 2007</primary_completion_date>
  <phase>Phase 2</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>Global assessment of tolerability by the investigator on a 4-point scale (good, satisfactory, not satisfactory and bad)</measure>
    <time_frame>Day 43</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>Up to day 50</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with clinically relevant changes in vital signs (blood pressure, pulse rate)</measure>
    <time_frame>Up to day 50</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with clinically relevant changes in clinical laboratory tests (haematology, clinical chemistry, and urinalysis)</measure>
    <time_frame>Up to day 50</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum measured concentration of the analyte in plasma (Cmax) at different time points</measure>
    <time_frame>Up to day 43</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time from last dosing to the maximum concentration of the analyte in plasma (tmax) at different time points</measure>
    <time_frame>Up to day 43</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration time curve of the analyte in plasma (AUC) at different time points</measure>
    <time_frame>Up to day 43</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Amount of the analyte that is eliminated in urine (Ae) at different time points</measure>
    <time_frame>Up to day 43</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fraction of parent drug eliminated in urine (fe) at different time points</measure>
    <time_frame>Up to day 43</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal clearance of the analyte (CLR) at different time points</measure>
    <time_frame>Up to day 43</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ (Cmin,ss)</measure>
    <time_frame>After the last dose on day 28 up to day 43</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average concentration of the analyte in plasma at steady state (Cavg)</measure>
    <time_frame>After the last dose on day 28 up to day 43</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal half-life of the analyte in plasma at steady state (t1/2,ss)</measure>
    <time_frame>After the last dose on day 28 up to day 43</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal rate constant in plasma at steady state (λz,ss)</measure>
    <time_frame>After last dose on day 28 up to day 43</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean residence time of the analyte in the body at steady state after oral administration (MRTpo,ss)</measure>
    <time_frame>After last dose on day 28 up to day 43</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent clearance of the analyte in plasma at steady state after extravascular multiple dose administration (CL/F,ss)</measure>
    <time_frame>After last dose on day 28 up to day 43</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution during the terminal phase λz at steady state following extravascular administration (Vz/F,ss)</measure>
    <time_frame>After last dose on day 28 up to day 43</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Predose concentration of the analyte in plasma (Cpre) at different time points immediately before administration of the Nth dose</measure>
    <time_frame>Up to day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Calculation of accumulation ratio of the analyte in plasma based on Cmax (RA,Cmax)</measure>
    <time_frame>Up to day 43</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Calculation of accumulation ratio of the analyte in plasma based on AUCτ (RA,AUCτ)</measure>
    <time_frame>Up to day 43</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimum dipeptidyl peptidase IV (DPP-IV) activity (Emin) at different time points</measure>
    <time_frame>Up to day 43</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to reach minimum DPP-IV activity (tmin) at different time points</measure>
    <time_frame>Up to day 43</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DPP-IV activity at different time points</measure>
    <time_frame>Up to day 43</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">72</enrollment>
  <condition>Diabetes Mellitus, Type 2</condition>
  <arm_group>
    <arm_group_label>Low dose of BI 1356 BS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Medium dose of BI 1356 BS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>High dose of BI 1356 BS</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>Low dose of BI 1356 BS</intervention_name>
    <arm_group_label>Low dose of BI 1356 BS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Medium dose of BI 1356 BS</intervention_name>
    <arm_group_label>Medium dose of BI 1356 BS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>High dose of BI 1356 BS</intervention_name>
    <arm_group_label>High dose of BI 1356 BS</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;
          -  Japanese patients with a diagnosis of type 2 diabetes mellitus treated with diet&#xD;
             and/or exercise only or with one or two oral hypoglycaemic agents except glitazones&#xD;
&#xD;
          -  Glycosylated haemoglobin A1 (HbA1c)&#xD;
&#xD;
               -  &lt;= 8.5% at screening for patients treated with diet and/or exercise and/or one&#xD;
                  oral hypoglycaemic agent or&#xD;
&#xD;
               -  &lt;= 8.0% at screening for patients treated with two oral hypoglycaemic agents&#xD;
&#xD;
          -  Age ≥21 and ≤ 70 years&#xD;
&#xD;
          -  BMI ≥ 17.6 and ≤ 35 kg/m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any finding of the medical examination including blood pressure, pulse rate and&#xD;
             electrocardiogram (ECG) deviating from normal and of not acceptable clinical relevance&#xD;
&#xD;
          -  Clinically relevant concomitant diseases like renal insufficiency, cardiac&#xD;
             insufficiency (NYHA II-IV), known cardiovascular diseases including hypertension&#xD;
             (&gt;150/95 mmHg), stroke, and transient ischemic attack (TIA).&#xD;
&#xD;
          -  Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic,&#xD;
             immunological or hormonal disorders, except for type 2 diabetes mellitus,&#xD;
             hyperlipidaemia and medically treated hypertension&#xD;
&#xD;
          -  Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or&#xD;
             relevant neurological disorders except polyneuropathy&#xD;
&#xD;
          -  Chronic or relevant acute infections (e.g., human immunodeficiency virus (HIV),&#xD;
             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 before drug administration except&#xD;
             anti-hypertensives, acetylsalicylic acid, and statins&#xD;
&#xD;
          -  Use of drugs decreasing blood glucose within 10 days before drug administration&#xD;
&#xD;
          -  Participation in another trial with an investigational drug within two months before&#xD;
             drug administration&#xD;
&#xD;
          -  Alcohol abuse&#xD;
&#xD;
          -  Drug abuse&#xD;
&#xD;
          -  Blood donation (100 mL or more within four weeks before drug administration)&#xD;
&#xD;
          -  Excessive physical activities (within one week before drug administration or during&#xD;
             the 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 such as aspartate aminotransferase (AST(serum&#xD;
             glutamate oxaloacetate transaminase/ SGOT)), alanine transaminase (ALT(serum glutamate&#xD;
             pyruvate transaminase/ SGPT)), alkaline phosphatase (γALP), and lactate dehydrogenase&#xD;
             (LDH)&#xD;
&#xD;
          -  Fasted blood glucose &gt;240 mg/dL (=13.3 mmol/L) on two consecutive days during washout&#xD;
&#xD;
          -  Serum creatinine above 1.3 mg/dL at screening&#xD;
&#xD;
          -  Pregnancy or child-bearing potential patients and breast-feeding 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;
      </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/1218/1218.12_U08-3213-01.pdf</url>
    <description>Related Info</description>
  </link>
  <link>
    <url>https://www.ncbi.nlm.nih.gov/pubmed/24393553</url>
    <description>Related Info</description>
  </link>
  <verification_date>December 2017</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>December 27, 2017</last_update_submitted>
  <last_update_submitted_qc>December 27, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">December 28, 2017</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/NCT02183324
org study id: 1218.12
nct id: NCT02183324
lead sponsor: 
Study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of BI 1356
      BS (0.5 mg, 2.5 mg, and 10 mg) administered orally once daily for 28 days in Japanese
      patients with type 2 diabetes mellitus.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: Global assessment of tolerability by the investigator on a 4-point scale (good, satisfactory, not satisfactory and bad)
time frame: Day 43
measure: Number of patients with adverse events
time frame: Up to day 50
measure: Number of patients with clinically relevant changes in vital signs (blood pressure, pulse rate)
time frame: Up to day 50
measure: Number of patients with clinically relevant changes in clinical laboratory tests (haematology, clinical chemistry, and urinalysis)
time frame: Up to day 50
measure: Maximum measured concentration of the analyte in plasma (Cmax) at different time points
time frame: Up to day 43
measure: Time from last dosing to the maximum concentration of the analyte in plasma (tmax) at different time points
time frame: Up to day 43
measure: Area under the concentration time curve of the analyte in plasma (AUC) at different time points
time frame: Up to day 43
measure: Amount of the analyte that is eliminated in urine (Ae) at different time points
time frame: Up to day 43
measure: Fraction of parent drug eliminated in urine (fe) at different time points
time frame: Up to day 43
measure: Renal clearance of the analyte (CLR) at different time points
time frame: Up to day 43
measure: Minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ (Cmin,ss)
time frame: After the last dose on day 28 up to day 43
measure: Average concentration of the analyte in plasma at steady state (Cavg)
time frame: After the last dose on day 28 up to day 43
measure: Terminal half-life of the analyte in plasma at steady state (t1/2,ss)
time frame: After the last dose on day 28 up to day 43
measure: Terminal rate constant in plasma at steady state (λz,ss)
time frame: After last dose on day 28 up to day 43
measure: Mean residence time of the analyte in the body at steady state after oral administration (MRTpo,ss)
time frame: After last dose on day 28 up to day 43
measure: Apparent clearance of the analyte in plasma at steady state after extravascular multiple dose administration (CL/F,ss)
time frame: After last dose on day 28 up to day 43
measure: Apparent volume of distribution during the terminal phase λz at steady state following extravascular administration (Vz/F,ss)
time frame: After last dose on day 28 up to day 43
measure: Predose concentration of the analyte in plasma (Cpre) at different time points immediately before administration of the Nth dose
time frame: Up to day 28
measure: Calculation of accumulation ratio of the analyte in plasma based on Cmax (RA,Cmax)
time frame: Up to day 43
measure: Calculation of accumulation ratio of the analyte in plasma based on AUCτ (RA,AUCτ)
time frame: Up to day 43
measure: Minimum dipeptidyl peptidase IV (DPP-IV) activity (Emin) at different time points
time frame: Up to day 43
measure: Time to reach minimum DPP-IV activity (tmin) at different time points
time frame: Up to day 43
measure: DPP-IV activity at different time points
time frame: Up to day 43
arm group label: Low dose of BI 1356 BS
arm group type: Experimental
arm group label: Medium dose of BI 1356 BS
arm group type: Experimental
arm group label: High dose of BI 1356 BS
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Low dose of BI 1356 BS
arm group label: Low dose of BI 1356 BS
intervention type: Drug
intervention name: Medium dose of BI 1356 BS
arm group label: Medium dose of BI 1356 BS
intervention type: Drug
intervention name: High dose of BI 1356 BS
arm group label: High dose of BI 1356 BS
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/1218/1218.12_U08-3213-01.pdf
description: Related Info
url: https://www.ncbi.nlm.nih.gov/pubmed/24393553
description: Related Info
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Linagliptin