<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/NCT02211963</url>
  </required_header>
  <id_info>
    <org_study_id>1224.3</org_study_id>
    <nct_id>NCT02211963</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Oral Doses of BI 44847 in Female and Male Patients With Type 2 Diabetes</brief_title>
  <official_title>Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Four Multiple Rising Oral Doses (50-800 mg b.i.d. or q.d. for 8 Days) of BI 44847 as Tablet in Female and Male Patients With Type 2 Diabetes</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;
      44847 following administration of multiple rising oral doses over 8 days in patients with&#xD;
      type 2 diabetes.&#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 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>Number of patients with adverse events</measure>
    <time_frame>up to 53 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with clinically significant findings in vital signs (blood pressure (BP), pulse rate (PR))</measure>
    <time_frame>up to 18 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with clinically relevant findings in 12-lead electrocardiogram (ECG)</measure>
    <time_frame>up to 18 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with clinically relevant laboratory findings</measure>
    <time_frame>up to 18 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessment of tolerability by investigator on a 4-point scale</measure>
    <time_frame>Day 18</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum concentration of the analyte in plasma for several time points (Cmax)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time from dosing to maximum concentration for several time points (tmax)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal half-life of the analyte in plasma for several time points (t1/2)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal rate constant in plasma for several time points (λz)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of analyte in plasma for several time points</measure>
    <time_frame>12 and 24 hours after drug administration on day 1 and 9</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve of the analyte in plasma for several time points (AUC)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Amount of analyte that is eliminated in urine for several time points (Ae)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fraction of analyte excreted unchanged in urine for several time points (fe)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal clearance of the analyte in plasma for several time points (CLR)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent clearance of the analyte in the plasma for several time points (CL/F)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution during the terminal phase λz following an extravascular dose for several time points (Vz/F)</measure>
    <time_frame>up to 72 hours after 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>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tmin,ss (time from dosing to minimum concentration during a dosing interval)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Predose concentration of the analyte in plasma at steady state immediately before administration of the next dose for several time points</measure>
    <time_frame>up to day 9</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRTpo,ss (mean residence time of the analyte in the body after 11 administrations (b.i.d.) and 6 administrations (q.d.) respectively, at steady state)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cavg (average concentration)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PTF (peak trough fluctuation)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation ratio (RA) based on Cmax</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation ratio (RA) based on AUC</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma glucose levels</measure>
    <time_frame>up to 15 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Amount of glucose excreted in urine</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>Diabetes Mellitus, Type 2</condition>
  <arm_group>
    <arm_group_label>BI 44847</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 44847</intervention_name>
    <arm_group_label>BI 44847</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 postmenopausal or hysterectomised female patients with proven diagnose of&#xD;
             type 2 diabetes mellitus treated with diet and exercise only or with one oral&#xD;
             hypoglycaemic agents besides glitazones&#xD;
&#xD;
          -  Glycosylated haemoglobin A1 (HbA1c) ≤ 8.5 % at screening for patients treated with&#xD;
             diet and exercise and/or one oral hypoglycaemic agent&#xD;
&#xD;
          -  Age ≥21 and Age ≤70 years (female hysterectomised and male patients) Age ≥60 and Age&#xD;
             ≤70 years (female postmenopausal patients)&#xD;
&#xD;
          -  BMI ≥18.5 and BMI ≤35 kg/m2 (Body Mass Index)&#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 BP, PR and ECG) deviating from&#xD;
             normal and of not acceptable clinical relevance&#xD;
&#xD;
          -  Clinically relevant concomitant diseases like renal insufficiency (creatinine&#xD;
             clearance &lt; 80 ml/min/173m**2), cardiac insufficiency New York Heart Association&#xD;
             II-IV, myocardial infarction, other known cardiovascular diseases including&#xD;
             hypertension &gt; 160/95mmHg, stroke and 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 and/or food which might reasonably influence the results of the trial&#xD;
             based on the knowledge at the time of protocol preparation within 10 days prior to&#xD;
             administration or during the trial&#xD;
&#xD;
          -  Antidiabetic treatment with more than one oral hypoglycaemic agent or insulin or&#xD;
             glitazones&#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;
          -  Use of drugs which might reasonably influence the results of the trial or that prolong&#xD;
             the QT/QTc interval based on the knowledge at the time of protocol preparation within&#xD;
             10 days prior to administration or during 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)&#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 (&gt;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 not willing to use adequate contraception (condom use plus another form&#xD;
             of 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;
          -  A marked baseline prolongation of QT/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;
             hypokalemia, family history of Long QT Syndrome)&#xD;
&#xD;
        For female patients:&#xD;
&#xD;
          -  Child bearing potential without hysterectomy&#xD;
&#xD;
          -  Positive pregnancy test&#xD;
&#xD;
          -  Lactation period&#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</url>
    <description>Related Info</description>
  </link>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>August 7, 2014</study_first_submitted>
  <study_first_submitted_qc>August 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 8, 2014</study_first_posted>
  <last_update_submitted>August 12, 2014</last_update_submitted>
  <last_update_submitted_qc>August 12, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 13, 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>
  <!-- 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/NCT02211963
org study id: 1224.3
nct id: NCT02211963
lead sponsor: 
Study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of BI
      44847 following administration of multiple rising oral doses over 8 days in patients with
      type 2 diabetes.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: Number of patients with adverse events
time frame: up to 53 days
measure: Number of patients with clinically significant findings in vital signs (blood pressure (BP), pulse rate (PR))
time frame: up to 18 days
measure: Number of patients with clinically relevant findings in 12-lead electrocardiogram (ECG)
time frame: up to 18 days
measure: Number of patients with clinically relevant laboratory findings
time frame: up to 18 days
measure: Assessment of tolerability by investigator on a 4-point scale
time frame: Day 18
measure: Maximum concentration of the analyte in plasma for several time points (Cmax)
time frame: up to 72 hours after drug administration
measure: Time from dosing to maximum concentration for several time points (tmax)
time frame: up to 72 hours after drug administration
measure: Terminal half-life of the analyte in plasma for several time points (t1/2)
time frame: up to 72 hours after drug administration
measure: Terminal rate constant in plasma for several time points (λz)
time frame: up to 72 hours after drug administration
measure: Concentration of analyte in plasma for several time points
time frame: 12 and 24 hours after drug administration on day 1 and 9
measure: Area under the concentration-time curve of the analyte in plasma for several time points (AUC)
time frame: up to 72 hours after drug administration
measure: Amount of analyte that is eliminated in urine for several time points (Ae)
time frame: up to 72 hours after drug administration
measure: Fraction of analyte excreted unchanged in urine for several time points (fe)
time frame: up to 72 hours after drug administration
measure: Renal clearance of the analyte in plasma for several time points (CLR)
time frame: up to 72 hours after drug administration
measure: Apparent clearance of the analyte in the plasma for several time points (CL/F)
time frame: up to 72 hours after drug administration
measure: Apparent volume of distribution during the terminal phase λz following an extravascular dose for several time points (Vz/F)
time frame: up to 72 hours after drug administration
measure: Cmin,ss (minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval)
time frame: up to 72 hours after drug administration
measure: tmin,ss (time from dosing to minimum concentration during a dosing interval)
time frame: up to 72 hours after drug administration
measure: Predose concentration of the analyte in plasma at steady state immediately before administration of the next dose for several time points
time frame: up to day 9
measure: MRTpo,ss (mean residence time of the analyte in the body after 11 administrations (b.i.d.) and 6 administrations (q.d.) respectively, at steady state)
time frame: up to 72 hours after drug administration
measure: Cavg (average concentration)
time frame: up to 72 hours after drug administration
measure: PTF (peak trough fluctuation)
time frame: up to 72 hours after drug administration
measure: Accumulation ratio (RA) based on Cmax
time frame: up to 72 hours after drug administration
measure: Accumulation ratio (RA) based on AUC
time frame: up to 72 hours after drug administration
measure: Plasma glucose levels
time frame: up to 15 hours after drug administration
measure: Amount of glucose excreted in urine
time frame: up to 72 hours after drug administration
arm group label: BI 44847
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: BI 44847
arm group label: BI 44847
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
description: Related Info
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2