<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/NCT02183350</url>
  </required_header>
  <id_info>
    <org_study_id>1218.2</org_study_id>
    <nct_id>NCT02183350</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BI 1356 BS in Patients With Type 2 Diabetes</brief_title>
  <official_title>Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Oral Doses (1, 2.5, 5, 10 and 25 mg q.d. for 12 Days) of BI 1356 BS as Powder in the Bottle (PIB) 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>
      The primary objective of the current study was to investigate the safety and tolerability of&#xD;
      BI 1356 BS following administration of multiple rising oral doses of 1 mg, 2.5 mg, 5 mg, and&#xD;
      10 mg over 12 days in male patients with type 2 diabetes.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>April 2005</start_date>
  <primary_completion_date type="Actual">August 2005</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>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>up to 28 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with abnormal findings in physical examination</measure>
    <time_frame>up to 28 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with abnormal changes in Vital signs (blood pressure (BP), pulse rate (PR))</measure>
    <time_frame>up to 28 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with abnormal changes in 12-lead ECG (electrocardiogram)</measure>
    <time_frame>up to 28 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with abnormal changes in laboratory parameters</measure>
    <time_frame>up to 28 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessment of tolerability by investigator on a 4-point scale</measure>
    <time_frame>up to 28 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cmax (maximum concentration of the analyte in plasma)</measure>
    <time_frame>predose, up to 456 h</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tmax (time from dosing to maximum concentration)</measure>
    <time_frame>predose, up to 456 h</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC (area under the concentration-time curve of the analyte in plasma)</measure>
    <time_frame>predose, up to 456 h</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ae (amount of analyte that is eliminated in urine)</measure>
    <time_frame>predose, up to 456 h</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>fe (fraction of analyte excreted in urine)</measure>
    <time_frame>up to 288 h</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CLR (renal clearance of the analyte in plasma)</measure>
    <time_frame>up to 288 h</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>predose, up to 456 h</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>predose, up to 456 h</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>λz,ss (terminal rate constant in plasma at steady state)</measure>
    <time_frame>predose, up to 456 h</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2,ss (terminal half-life of the analyte in plasma at steady state)</measure>
    <time_frame>predose, up to 456 h</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>predose, up to 456 h</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>predose, up to 456 h</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>predose, up to 456 h</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in PTF (peak trough fluctuation)</measure>
    <time_frame>up to 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>RA,Cmax based on Cmax</measure>
    <time_frame>predose, up to 456 h</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>RA,AUC based on AUCτ</measure>
    <time_frame>predose, up to 456 h</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Dipeptidyl-Peptidase IV (DPP-IV) activity in plasma</measure>
    <time_frame>predose, up to 456 h</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in plasma glucose levels</measure>
    <time_frame>up to 13 days</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">47</enrollment>
  <condition>Diabetes Mellitus, Type 2</condition>
  <arm_group>
    <arm_group_label>BI 1356 BS - single rising 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 - single rising dose</intervention_name>
    <arm_group_label>BI 1356 BS - single rising 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 patients with proven diagnose of type 2 diabetes mellitus treated with diet and&#xD;
        exercise only or with one (or two) oral hypoglycaemic 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;
          -  Age ≥21 and Age ≤65 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 GCP and the local legislation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any finding of the medical examination (including Blood Pressure (BP), Pulse Rate (PR)&#xD;
             and Electrocardiogram (ECG)) deviating from normal and of not acceptable clinical&#xD;
             relevance&#xD;
&#xD;
          -  Clinically relevant concomitant diseases like renal insufficiency, cardiac&#xD;
             insufficiency New York Heart Association (NYHA) II-IV, known cardiovascular diseases&#xD;
             including hypertension &gt; 160/110 mmHg, stroke and Transient ischaemic attack (TIA)&#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. 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 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 60 g/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 that is of not acceptable clinical&#xD;
             relevance&#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;
          -  Any ECG value outside of the reference range and of clinical relevance including, but&#xD;
             not limited to QRS interval &gt; 120 ms or QTcB &gt; 450 ms or QT &gt;500 ms&#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;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <link>
    <url>http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/1218/1218.2_U06-1139.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/NCT02183350
org study id: 1218.2
nct id: NCT02183350
lead sponsor: 
The primary objective of the current study was to investigate the safety and tolerability of
      BI 1356 BS following administration of multiple rising oral doses of 1 mg, 2.5 mg, 5 mg, and
      10 mg over 12 days in male patients with type 2 diabetes.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: Double
measure: Number of patients with adverse events
time frame: up to 28 days
measure: Number of patients with abnormal findings in physical examination
time frame: up to 28 days
measure: Number of patients with abnormal changes in Vital signs (blood pressure (BP), pulse rate (PR))
time frame: up to 28 days
measure: Number of patients with abnormal changes in 12-lead ECG (electrocardiogram)
time frame: up to 28 days
measure: Number of patients with abnormal changes in laboratory parameters
time frame: up to 28 days
measure: Assessment of tolerability by investigator on a 4-point scale
time frame: up to 28 days
measure: Cmax (maximum concentration of the analyte in plasma)
time frame: predose, up to 456 h
measure: tmax (time from dosing to maximum concentration)
time frame: predose, up to 456 h
measure: AUC (area under the concentration-time curve of the analyte in plasma)
time frame: predose, up to 456 h
measure: Ae (amount of analyte that is eliminated in urine)
time frame: predose, up to 456 h
measure: fe (fraction of analyte excreted in urine)
time frame: up to 288 h
measure: CLR (renal clearance of the analyte in plasma)
time frame: up to 288 h
measure: Cmin,ss (minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval)
time frame: predose, up to 456 h
measure: Cpre,N (predose concentration of the analyte in plasma at steady state immediately before administration of the next dose N)
time frame: predose, up to 456 h
measure: λz,ss (terminal rate constant in plasma at steady state)
time frame: predose, up to 456 h
measure: t1/2,ss (terminal half-life of the analyte in plasma at steady state)
time frame: predose, up to 456 h
measure: MRTpo,ss (mean residence time of the analyte in the body after 12 administrations at steady state)
time frame: predose, up to 456 h
measure: CL/F,ss (apparent clearance of the analyte in the plasma after extravascular administration at steady state)
time frame: predose, up to 456 h
measure: Vz/F,ss (apparent volume of distribution during the terminal phase λz following an extravascular dose at steady state)
time frame: predose, up to 456 h
measure: Changes in PTF (peak trough fluctuation)
time frame: up to 28 days
measure: RA,Cmax based on Cmax
time frame: predose, up to 456 h
measure: RA,AUC based on AUCτ
time frame: predose, up to 456 h
measure: Changes in Dipeptidyl-Peptidase IV (DPP-IV) activity in plasma
time frame: predose, up to 456 h
measure: Change in plasma glucose levels
time frame: up to 13 days
arm group label: BI 1356 BS - single rising dose
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: BI 1356 BS - single rising dose
arm group label: BI 1356 BS - single rising dose
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: Male
minimum age: 21 Years
maximum age: 65 Years
healthy volunteers: No
url: http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/1218/1218.2_U06-1139.pdf
description: Related Info
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Linagliptin