<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/NCT02217644</url>
  </required_header>
  <id_info>
    <org_study_id>1262.1</org_study_id>
    <nct_id>NCT02217644</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability and Pharmacokinetics of BI 653048 H3PO4 Oral Drinking Solution in Healthy Male Volunteers</brief_title>
  <official_title>Safety, Tolerability and Pharmacokinetics of BI 653048 H3PO4 Oral Drinking Solution in Healthy Male Volunteers (Dose Range: 0.1 mg - 1500 mg). A Singleblind (Within Dose Groups), Randomised, Placebo-controlled Within Dose Groups, Single Rising Dose Phase I Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      -  Investigation of safety and tolerability of BI 653048 H3PO4 following the administration&#xD;
           of single rising doses of an aqueous solution in healthy male subjects&#xD;
&#xD;
        -  Pharmacokinetic and pharmacodynamic characteristics of BI 653048, including the&#xD;
           investigation of dose proportionality&#xD;
&#xD;
        -  Investigation of relative bioavailability of capsules versus aqueous solution&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2008</start_date>
  <primary_completion_date type="Actual">June 2009</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>Single</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of patients with clinically significant findings in vital signs</measure>
    <time_frame>up to 10 days after drug administration</time_frame>
    <description>blood pressure (BP), pulse rate (PR) respiratory rate (RR), oral body temperature (T), 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 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 drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>up to 10 days after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessment of tolerability performed by the investigator on a four-point scale</measure>
    <time_frame>up to 10 days after drug administration</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cmax (maximum measured concentration of the analyte in plasma)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tmax (time from dosing to maximum measured concentration)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>%AUCtz-∞ (the percentage of the AUC0-∞ that is obtained by extrapolation)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUCt1-t2 (Area under the concentration-time curve of the analyte in plasma over the time interval t1 to t2)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>λz (terminal rate constant in plasma)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2 (terminal half-life of the analyte in plasma)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRTp.o. (mean residence time of the analyte in the body after oral administration)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL/F (total/apparent clearance of the analyte in plasma after extravascular administration)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Aet1-t2 (amount of analyte eliminated in urine from the time point t1 to time point t2)</measure>
    <time_frame>up to 48 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>fet1-t2 (fraction of analyte eliminated in urine from time point t1 to time point t2)</measure>
    <time_frame>up to 48 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CLR,t1-t2 (renal clearance of the analyte from the time point t1 until the time point t2)</measure>
    <time_frame>up to 48 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose-normalised Cmax</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose-normalized AUC0-∞</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Emax (maximum measured concentration of the biomarker in blood or serum)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Emin (minimum measured concentration of the biomarker in blood or serum)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmin (time from dosing to minimum measured concentration of the biomarker)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax (time from dosing to maximum measured concentration of the biomarker)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUECt1-t2 (area under the concentration-time curve of the biomarker in the blood over the time interval from t1 to t2)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUECbelow_base (area under the baseline corrected concentration-time curve of the biomarker)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUECabove_base (area above the baseline corrected concentration-time curve of the biomarker)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expression of glucocorticoid responsive genes</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">80</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>BI 653048 H3PO4 solution</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>single rising doses</description>
  </arm_group>
  <arm_group>
    <arm_group_label>BI 653048 H3PO4 low dose capsule</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>BI 653048 H3PO4 high dose capsule</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 653048 H3PO4 solution</intervention_name>
    <arm_group_label>BI 653048 H3PO4 solution</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 653048 H3PO4 low dose capsule</intervention_name>
    <arm_group_label>BI 653048 H3PO4 low dose capsule</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 653048 H3PO4 high dose capsule</intervention_name>
    <arm_group_label>BI 653048 H3PO4 high dose capsule</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 males according to the following criteria: Based upon a complete medical&#xD;
             history, including the physical examination, vital signs (blood pressure (BP), pulse&#xD;
             rate (PR)), 12-lead electrocardiogram (ECG), clinical laboratory tests&#xD;
&#xD;
          -  Age ≥21 years and ≤50 years&#xD;
&#xD;
          -  Body Mass Index (BMI) ≥18.5 kg/m2 and BMI ≤29.9 kg/m2&#xD;
&#xD;
          -  Signed and dated written informed consent prior to admission to the trial 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 BP, PR and ECG) deviating from&#xD;
             normal and of clinical relevance&#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) or 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/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 one month or less than&#xD;
             10 half-lives of the respective drug prior to administration or during the 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;
          -  Participation in another trial with an investigational drug within 2 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 4 weeks prior to administration or during the&#xD;
             trial)&#xD;
&#xD;
          -  Excessive physical activities (within 1 week prior to administration or during the&#xD;
             trial)&#xD;
&#xD;
          -  Any laboratory value outside the reference range that was of clinical relevance&#xD;
&#xD;
          -  Inability to comply with dietary regimen of trial site&#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 Torsades des Pointes (e.g., heart failure,&#xD;
             hypokalaemia, family history of Long QT Syndrome)&#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 trial period from the time of the&#xD;
             first intake of trial drug until 3 months after the last intake&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>21 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>
  <!-- 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/NCT02217644
org study id: 1262.1
nct id: NCT02217644
lead sponsor: 
-  Investigation of safety and tolerability of BI 653048 H3PO4 following the administration
           of single rising doses of an aqueous solution in healthy male subjects

        -  Pharmacokinetic and pharmacodynamic characteristics of BI 653048, including the
           investigation of dose proportionality

        -  Investigation of relative bioavailability of capsules versus aqueous solution
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single
measure: Number of patients with clinically significant findings in vital signs
time frame: up to 10 days after drug administration
description: blood pressure (BP), pulse rate (PR) respiratory rate (RR), oral body temperature (T), orthostatic test
measure: Number of patients with clinically significant findings in ECG
time frame: up to 10 days after drug administration
measure: Number of patients with clinically significant findings in laboratory tests
time frame: up to 10 days after drug administration
measure: Number of patients with adverse events
time frame: up to 10 days after drug administration
measure: Assessment of tolerability performed by the investigator on a four-point scale
time frame: up to 10 days after drug administration
measure: Cmax (maximum measured concentration of the analyte in plasma)
time frame: up to 72 hours after drug administration
measure: tmax (time from dosing to maximum measured concentration)
time frame: up to 72 hours after drug administration
measure: AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
time frame: up to 72 hours after drug administration
measure: %AUCtz-∞ (the percentage of the AUC0-∞ that is obtained by extrapolation)
time frame: up to 72 hours after drug administration
measure: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point)
time frame: up to 72 hours after drug administration
measure: AUCt1-t2 (Area under the concentration-time curve of the analyte in plasma over the time interval t1 to t2)
time frame: up to 72 hours after drug administration
measure: λz (terminal rate constant in plasma)
time frame: up to 72 hours after drug administration
measure: t1/2 (terminal half-life of the analyte in plasma)
time frame: up to 72 hours after drug administration
measure: MRTp.o. (mean residence time of the analyte in the body after oral administration)
time frame: up to 72 hours after drug administration
measure: CL/F (total/apparent clearance of the analyte in plasma after extravascular administration)
time frame: up to 72 hours after drug administration
measure: Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)
time frame: up to 72 hours after drug administration
measure: Aet1-t2 (amount of analyte eliminated in urine from the time point t1 to time point t2)
time frame: up to 48 hours after drug administration
measure: fet1-t2 (fraction of analyte eliminated in urine from time point t1 to time point t2)
time frame: up to 48 hours after drug administration
measure: CLR,t1-t2 (renal clearance of the analyte from the time point t1 until the time point t2)
time frame: up to 48 hours after drug administration
measure: Dose-normalised Cmax
time frame: up to 72 hours after drug administration
measure: Dose-normalized AUC0-∞
time frame: up to 72 hours after drug administration
measure: Emax (maximum measured concentration of the biomarker in blood or serum)
time frame: up to 72 hours after drug administration
measure: Emin (minimum measured concentration of the biomarker in blood or serum)
time frame: up to 72 hours after drug administration
measure: Tmin (time from dosing to minimum measured concentration of the biomarker)
time frame: up to 72 hours after drug administration
measure: Tmax (time from dosing to maximum measured concentration of the biomarker)
time frame: up to 72 hours after drug administration
measure: AUECt1-t2 (area under the concentration-time curve of the biomarker in the blood over the time interval from t1 to t2)
time frame: up to 72 hours after drug administration
measure: AUECbelow_base (area under the baseline corrected concentration-time curve of the biomarker)
time frame: up to 72 hours after drug administration
measure: AUECabove_base (area above the baseline corrected concentration-time curve of the biomarker)
time frame: up to 72 hours after drug administration
measure: Expression of glucocorticoid responsive genes
time frame: up to 72 hours after drug administration
arm group label: BI 653048 H3PO4 solution
arm group type: Experimental
description: single rising doses
arm group label: BI 653048 H3PO4 low dose capsule
arm group type: Experimental
arm group label: BI 653048 H3PO4 high dose capsule
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: BI 653048 H3PO4 solution
arm group label: BI 653048 H3PO4 solution
intervention type: Drug
intervention name: BI 653048 H3PO4 low dose capsule
arm group label: BI 653048 H3PO4 low dose capsule
intervention type: Drug
intervention name: BI 653048 H3PO4 high dose capsule
arm group label: BI 653048 H3PO4 high dose capsule
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: Male
minimum age: 21 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor