<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/NCT02217631</url>
  </required_header>
  <id_info>
    <org_study_id>1262.2</org_study_id>
    <nct_id>NCT02217631</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BI 653048 BS H3PO4 Capsule Multiple Rising Doses in Healthy Male Volunteers</brief_title>
  <official_title>Safety, Tolerability, Pharmacokinetics and Pharmacodynamics (Biomarkers) of BI 653048 BS H3PO4 Capsule Formulation Administered as Multiple Doses of 25 mg to 200 mg qd for 10 Days. A Randomised, Double-blind Within Dose Groups, Placebo-controlled, Multiple Rising Dose Trial With Open-label Active Comparator</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 objectives of the trial were to assess safety, tolerability, pharmacokinetics, and&#xD;
      pharmacodynamics of multiple rising doses of BI 653048 BS H3PO4 compared with prednisolone.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2009</start_date>
  <primary_completion_date type="Actual">March 2010</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 day 14</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with clinically significant findings in vital signs</measure>
    <time_frame>up to 10 days after last drug administration</time_frame>
    <description>blood pressure, pulse rate, body temperature, orthostatic test</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with clinically significant findings in ECG</measure>
    <time_frame>up to 10 days after last drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with clinically significant findings in laboratory tests</measure>
    <time_frame>up to 10 days after last drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessment of tolerability by the investigator on a four-point scale</measure>
    <time_frame>up to 10 days after last drug administration</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum measured concentration of the analyte in plasma at different time points (Cmax)</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>time from dosing to maximum measured concentration of the analyte at different time points (tmax)</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve of the analyte in the plasma over time interval from 0 to the last measurable time point of the dose at different time points (AUC0-tz)</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity at different time points (AUC0-∞)</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of the AUC0-∞ that is obtained by extrapolation at different time points (%AUCtz-∞)</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal phase elimination rate constant at different time points (λz)</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean residence time of the analyte in the body after oral administration at different time points (MRTpo)</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal phase elimination half life at different time points (t1/2)</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent clearance of the analyte in plasma following extravascular administration at steady state (CL/Fss)</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution during the terminal phase λz following an extravascular dose at steady state (Vz/Fss)</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimum plasma concentration at steady state (Cmin,ss)</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose-normalized Cmax at steady state (Cmax/Dss)</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose-normalised AUC0-∞ at steady state (AUC0-∞/Dss)</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation index of the analyte when comparing AUCτ (RA,AUCτ)</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation index of the analyte when comparing Cmax (RA,Cmax)</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Linearity index (LI)</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Amount of analyte excreted in urine unchanged from t1 to t2 interval at different time points (Aet1-t2)</measure>
    <time_frame>up to day 11</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal clearance of the unchanged analyte at different time points (CLr)</measure>
    <time_frame>up to day 11</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the serum biomarker concentration-time curve after the Nth dose (AUECN)</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the baseline (before dose level) but above serum biomarker concentration-time curve after the Nth dose (AUECbelow_base)</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimum measured serum concentration of the biomarkers after the Nth dose (Emin,N)</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum measured serum concentration of the biomarkers after the Nth dose (Emax,N)</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum biomarker concentration after the (N-1)th dose but before the Nth dose (Epre,N)</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measured value of the biomarkers in biological matrix at the set time point after Nth dose (EN)</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oral glucose insulin sensitivity (OGIS) index</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Homeostasis model assessment (HOMA) value</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">140</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>BI 653048 BS H3PO4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>dose escalation</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Prednisolone low dose</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Prednisolone high dose</arm_group_label>
    <arm_group_type>Active Comparator</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 653048 BS H3PO4</intervention_name>
    <arm_group_label>BI 653048 BS H3PO4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisolone low dose</intervention_name>
    <arm_group_label>Prednisolone low dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisolone high dose</intervention_name>
    <arm_group_label>Prednisolone 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;
          -  Healthy male subjects based on a complete medical history, physical examination, vital&#xD;
             signs (blood pressure and pulse rate), 12-lead ECG, and clinical laboratory tests&#xD;
&#xD;
          -  Age of 18 to 50 years&#xD;
&#xD;
          -  Body mass index (BMI) of 18.5 to 29.9 kg/m2&#xD;
&#xD;
          -  Signed and dated written informed consent in accordance with Good Clinical Practice&#xD;
             and the local legislation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any clinically relevant deviation from normal in the medical examination including&#xD;
             blood pressure, pulse rate, and ECG&#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 or 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;
             half-lives of the respective drug before first treatment with study drug or during&#xD;
             trial&#xD;
&#xD;
          -  Use of drugs which might reasonably influence the results of the trial or which&#xD;
             prolong the QT/QTc interval within 10 days before first treatment with study drug or&#xD;
             during trial&#xD;
&#xD;
          -  Participation in another trial with an investigational drug within 30 days before&#xD;
             first treatment with study drug or during trial&#xD;
&#xD;
          -  Smoker (more than 10 cigarettes, 3 cigars, or 3 pipes per day)&#xD;
&#xD;
          -  Inability to refrain from smoking beginning from 1 day before first treatment with&#xD;
             study drug until discharge from the clinical unit&#xD;
&#xD;
          -  Alcohol abuse (more than 60 grams per day)&#xD;
&#xD;
          -  Drug abuse&#xD;
&#xD;
          -  Blood donation of more than 100 mL within 4 weeks before first treatment with study&#xD;
             drug or during trial&#xD;
&#xD;
          -  Excessive physical activities within 1 week before first treatment with study drug or&#xD;
             during trial&#xD;
&#xD;
          -  Any laboratory value outside the reference range and of clinical relevance&#xD;
&#xD;
          -  Inability to comply with dietary regimen of trial site&#xD;
&#xD;
          -  A marked baseline prolongation of the QT/QTc interval (e.g. QTc intervals that are&#xD;
             repeatedly longer than 450 ms)&#xD;
&#xD;
          -  A history of additional risk factors for torsades de points (e.g. heart failure,&#xD;
             hypokalaemia, or family history of Long QT syndrome&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</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 14, 2014</study_first_submitted>
  <study_first_submitted_qc>August 14, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 15, 2014</study_first_posted>
  <last_update_submitted>August 14, 2014</last_update_submitted>
  <last_update_submitted_qc>August 14, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 15, 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>Prednisolone</mesh_term>
    <mesh_term>Methylprednisolone Acetate</mesh_term>
    <mesh_term>Methylprednisolone</mesh_term>
    <mesh_term>Methylprednisolone Hemisuccinate</mesh_term>
    <mesh_term>Prednisolone acetate</mesh_term>
    <mesh_term>Prednisolone hemisuccinate</mesh_term>
    <mesh_term>Prednisolone phosphate</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/NCT02217631
org study id: 1262.2
nct id: NCT02217631
lead sponsor: 
The objectives of the trial were to assess safety, tolerability, pharmacokinetics, and
      pharmacodynamics of multiple rising doses of BI 653048 BS H3PO4 compared with prednisolone.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: Number of patients with adverse events
time frame: up to day 14
measure: Number of patients with clinically significant findings in vital signs
time frame: up to 10 days after last drug administration
description: blood pressure, pulse rate, body temperature, orthostatic test
measure: Number of patients with clinically significant findings in ECG
time frame: up to 10 days after last drug administration
measure: Number of patients with clinically significant findings in laboratory tests
time frame: up to 10 days after last drug administration
measure: Assessment of tolerability by the investigator on a four-point scale
time frame: up to 10 days after last drug administration
measure: Maximum measured concentration of the analyte in plasma at different time points (Cmax)
time frame: up to day 13
measure: time from dosing to maximum measured concentration of the analyte at different time points (tmax)
time frame: up to day 13
measure: Area under the concentration-time curve of the analyte in the plasma over time interval from 0 to the last measurable time point of the dose at different time points (AUC0-tz)
time frame: up to day 13
measure: Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity at different time points (AUC0-∞)
time frame: up to day 13
measure: Percentage of the AUC0-∞ that is obtained by extrapolation at different time points (%AUCtz-∞)
time frame: up to day 13
measure: Terminal phase elimination rate constant at different time points (λz)
time frame: up to day 13
measure: Mean residence time of the analyte in the body after oral administration at different time points (MRTpo)
time frame: up to day 13
measure: Terminal phase elimination half life at different time points (t1/2)
time frame: up to day 13
measure: Apparent clearance of the analyte in plasma following extravascular administration at steady state (CL/Fss)
time frame: up to day 13
measure: Apparent volume of distribution during the terminal phase λz following an extravascular dose at steady state (Vz/Fss)
time frame: up to day 13
measure: Minimum plasma concentration at steady state (Cmin,ss)
time frame: up to day 13
measure: Dose-normalized Cmax at steady state (Cmax/Dss)
time frame: up to day 13
measure: Dose-normalised AUC0-∞ at steady state (AUC0-∞/Dss)
time frame: up to day 13
measure: Accumulation index of the analyte when comparing AUCτ (RA,AUCτ)
time frame: up to day 13
measure: Accumulation index of the analyte when comparing Cmax (RA,Cmax)
time frame: up to day 13
measure: Linearity index (LI)
time frame: up to day 13
measure: Amount of analyte excreted in urine unchanged from t1 to t2 interval at different time points (Aet1-t2)
time frame: up to day 11
measure: Renal clearance of the unchanged analyte at different time points (CLr)
time frame: up to day 11
measure: Area under the serum biomarker concentration-time curve after the Nth dose (AUECN)
time frame: up to day 13
measure: Area under the baseline (before dose level) but above serum biomarker concentration-time curve after the Nth dose (AUECbelow_base)
time frame: up to day 13
measure: Minimum measured serum concentration of the biomarkers after the Nth dose (Emin,N)
time frame: up to day 13
measure: Maximum measured serum concentration of the biomarkers after the Nth dose (Emax,N)
time frame: up to day 13
measure: Serum biomarker concentration after the (N-1)th dose but before the Nth dose (Epre,N)
time frame: up to day 13
measure: Measured value of the biomarkers in biological matrix at the set time point after Nth dose (EN)
time frame: up to day 13
measure: Oral glucose insulin sensitivity (OGIS) index
time frame: up to day 13
measure: Homeostasis model assessment (HOMA) value
time frame: up to day 13
arm group label: BI 653048 BS H3PO4
arm group type: Experimental
description: dose escalation
arm group label: Prednisolone low dose
arm group type: Active Comparator
arm group label: Prednisolone high dose
arm group type: Active Comparator
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: BI 653048 BS H3PO4
arm group label: BI 653048 BS H3PO4
intervention type: Drug
intervention name: Prednisolone low dose
arm group label: Prednisolone low dose
intervention type: Drug
intervention name: Prednisolone high dose
arm group label: Prednisolone high dose
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor
mesh term: Prednisolone
mesh term: Methylprednisolone Acetate
mesh term: Methylprednisolone
mesh term: Methylprednisolone Hemisuccinate
mesh term: Prednisolone acetate
mesh term: Prednisolone hemisuccinate
mesh term: Prednisolone phosphate