<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/NCT03754959</url>
  </required_header>
  <id_info>
    <org_study_id>1402-0002</org_study_id>
    <secondary_id>2018-000389-12</secondary_id>
    <nct_id>NCT03754959</nct_id>
  </id_info>
  <brief_title>This Study in Healthy Men Tests How Different Doses of BI 1358894 Are Taken up in the Body and How Well They Are Tolerated. The Study Also Tests How BI 1358894 Affects the Way the Body Breaks Down Midazolam</brief_title>
  <official_title>Safety, Tolerability, and Pharmacokinetics of Multiple Rising Oral Doses of BI 1358894 (Double-blind, Randomised, Placebo-controlled, Parallel-group Design) and Evaluation of Midazolam Interaction (Nested, Open, Fixed-sequence, Intra-individual Comparison) in Healthy Male Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of the trial is to investigate the safety and tolerability of BI&#xD;
      1358894 in healthy male subjects following oral administration of multiple rising doses over&#xD;
      14 days.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 18, 2018</start_date>
  <completion_date type="Actual">July 22, 2019</completion_date>
  <primary_completion_date type="Actual">July 22, 2019</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 (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of subjects with on-treatment drug-related AEs</measure>
    <time_frame>up to 32 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve of BI 1358894 in plasma over a time interval 0 to 24 h after administration of the first dose</measure>
    <time_frame>up to 24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum measured concentration of BI 1358894 in plasma</measure>
    <time_frame>up to 32 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve of BI 1358894 in plasma at steady state over a uniform dosing interval τ</measure>
    <time_frame>up to 32 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum measured concentration of BI 1358894 in plasma at steady state over a uniform dosing interval τ</measure>
    <time_frame>up to 32 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve of midazolam in plasma over the time interval from 0 to the last quantifiable data point</measure>
    <time_frame>up to 32 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum measured concentration of the analyte in plasma</measure>
    <time_frame>up to 32 days</time_frame>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Dose Group 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Group 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Group 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Group 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Group 5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 1358894</intervention_name>
    <description>Film-coated tablet</description>
    <arm_group_label>Dose Group 1</arm_group_label>
    <arm_group_label>Dose Group 2</arm_group_label>
    <arm_group_label>Dose Group 3</arm_group_label>
    <arm_group_label>Dose Group 4</arm_group_label>
    <arm_group_label>Dose Group 5</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Film-coated tablet</description>
    <arm_group_label>Dose Group 1</arm_group_label>
    <arm_group_label>Dose Group 2</arm_group_label>
    <arm_group_label>Dose Group 3</arm_group_label>
    <arm_group_label>Dose Group 4</arm_group_label>
    <arm_group_label>Dose Group 5</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Midazolam</intervention_name>
    <description>Solution for injection</description>
    <arm_group_label>Dose Group 1</arm_group_label>
    <arm_group_label>Dose Group 2</arm_group_label>
    <arm_group_label>Dose Group 3</arm_group_label>
    <arm_group_label>Dose Group 4</arm_group_label>
    <arm_group_label>Dose Group 5</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male subjects according to the investigator's assessment, based on a complete&#xD;
             medical history including a physical examination, vital signs (Blood Pressure (BP),&#xD;
             Pulse Rate (PR)), 12-lead Electrocardiogram (ECG), and clinical laboratory tests&#xD;
&#xD;
          -  Age of 18 to 45 years (incl.)&#xD;
&#xD;
          -  Body Mass Index (BMI) of 18.5 to 29.9 kg/m2 (incl.)&#xD;
&#xD;
          -  Signed and dated written informed consent prior to admission to the study in&#xD;
             accordance with Good Clinical Practice (GCP) and local legislation&#xD;
&#xD;
          -  Willingness to comply with contraception requirements. Subjects who are sexually&#xD;
             active must use adequate contraception with their female partner throughout the study&#xD;
             and until one month after the last administration of trial medication. Adequate&#xD;
             methods are:&#xD;
&#xD;
               -  Sexual abstinence or&#xD;
&#xD;
               -  A vasectomy performed at least 1 year prior to screening (with medical assessment&#xD;
                  of the surgical success) or&#xD;
&#xD;
               -  Surgical sterilisation (including bilateral tubal occlusion, hysterectomy or&#xD;
                  bilateral oophorectomy) of the subject's female partner or&#xD;
&#xD;
               -  The use of condoms, if the female partner uses an adequate contraception method&#xD;
                  in addition, e.g., intrauterine device (IUD), hormonal contraception (e.g.&#xD;
                  implants, injectables, combined oral or vaginal contraceptives) that started at&#xD;
                  least 2 months prior to first drug administration, or barrier method (e.g.&#xD;
                  diaphragm with spermicide) Unprotected sexual intercourse with a female partner&#xD;
                  is not allowed throughout the study and until one month after the last&#xD;
                  administration of trial medication.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any finding in the medical examination (including Blood Pressure (BP), Pulse Rate (PR)&#xD;
             or Electrocardiogram (ECG)) is deviating from normal and judged as clinically relevant&#xD;
             by the investigator&#xD;
&#xD;
          -  Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg,&#xD;
             diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the&#xD;
             range of 50 to 90 beats per minute (bpm)&#xD;
&#xD;
          -  C-Reactive Protein &gt; upper limit of normal (ULN), erythrocyte sedimentation rate (ESR)&#xD;
             ≥15 millimeters/h, liver or kidney parameter above ULN, or any other laboratory value&#xD;
             outside the reference range that the investigator considers to be of clinical&#xD;
             relevance&#xD;
&#xD;
          -  Positive or missing faecal occult blood test (retest allowed)&#xD;
&#xD;
          -  Positive testing for faecal calprotectin (retest allowed)&#xD;
&#xD;
          -  Any evidence of a concomitant disease judged as clinically relevant by the&#xD;
             investigator&#xD;
&#xD;
          -  Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic,&#xD;
             immunological or hormonal disorders&#xD;
&#xD;
          -  Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with&#xD;
             the pharmacokinetics of the trial medication (except appendectomy and simple hernia&#xD;
             repair)&#xD;
&#xD;
          -  Diseases of the central nervous system (including but not limited to any kind of&#xD;
             seizures or stroke), and other relevant neurological or psychiatric 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 the trial&#xD;
             medication or its excipients)&#xD;
&#xD;
          -  Use of drugs within 30 days prior to administration of trial medication that might&#xD;
             reasonably influence the results of the trial (incl. QT/QTc interval prolongation)&#xD;
&#xD;
          -  Participation in another trial where an investigational drug has been administered&#xD;
             within 60 days prior to planned administration of trial medication, or current&#xD;
             participation in another trial involving administration of investigational drug&#xD;
&#xD;
          -  Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)&#xD;
&#xD;
          -  Inability to refrain from smoking during in-house confinement&#xD;
&#xD;
          -  Alcohol abuse (consumption of more than 30 g per day)&#xD;
&#xD;
          -  Drug abuse or positive drug screening&#xD;
&#xD;
          -  Blood donation of more than 100 mL within 30 days prior to administration of trial&#xD;
             medication or intended donation during the trial&#xD;
&#xD;
          -  Intention to perform excessive physical activities within one week prior to&#xD;
             administration of trial medication or during the trial&#xD;
&#xD;
          -  Inability to comply with dietary regimen of trial site&#xD;
&#xD;
          -  A marked baseline prolongation of QT/QTc interval (such as QTc intervals that are&#xD;
             repeatedly greater than 450 ms) or any other relevant Electrocardiogram (ECG) finding&#xD;
             at screening&#xD;
&#xD;
          -  A history of additional risk factors for Torsades de Pointes (such as heart failure,&#xD;
             hypokalaemia, or family history of Long QT Syndrome)&#xD;
&#xD;
          -  Subject is assessed as unsuitable for inclusion by the investigator, for instance,&#xD;
             because considered not able to understand and comply with study requirements, or has a&#xD;
             condition that would not allow safe participation in the study&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>CRS Clinical Research Services Mannheim GmbH</name>
      <address>
        <city>Mannheim</city>
        <zip>68167</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>November 26, 2018</study_first_submitted>
  <study_first_submitted_qc>November 26, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 27, 2018</study_first_posted>
  <last_update_submitted>July 29, 2020</last_update_submitted>
  <last_update_submitted_qc>July 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 30, 2020</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>Midazolam</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions:&#xD;
Studies in products where Boehringer Ingelheim is not the license holder;&#xD;
studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials;&#xD;
Studies conducted in a single center or targeting rare diseases (because of limitations with anonymization).&#xD;
Requestors can use the following link http:// trials.boehringer-ingelheim.com/ to:&#xD;
find information in order to request access to clinical study data, for listed studies.&#xD;
request access to clinical study documents that meet criteria, and upon a signed 'Document Sharing Agreement.</ipd_description>
  </patient_data>
  <!-- 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/NCT03754959
org study id: 1402-0002
secondary id: 2018-000389-12
nct id: NCT03754959
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
The primary objective of the trial is to investigate the safety and tolerability of BI
      1358894 in healthy male subjects following oral administration of multiple rising doses over
      14 days.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Number of subjects with on-treatment drug-related AEs
time frame: up to 32 days
measure: Area under the concentration-time curve of BI 1358894 in plasma over a time interval 0 to 24 h after administration of the first dose
time frame: up to 24 hours
measure: Maximum measured concentration of BI 1358894 in plasma
time frame: up to 32 days
measure: Area under the concentration-time curve of BI 1358894 in plasma at steady state over a uniform dosing interval τ
time frame: up to 32 days
measure: Maximum measured concentration of BI 1358894 in plasma at steady state over a uniform dosing interval τ
time frame: up to 32 days
measure: Area under the concentration-time curve of midazolam in plasma over the time interval from 0 to the last quantifiable data point
time frame: up to 32 days
measure: Maximum measured concentration of the analyte in plasma
time frame: up to 32 days
arm group label: Dose Group 1
arm group type: Experimental
arm group label: Dose Group 2
arm group type: Experimental
arm group label: Dose Group 3
arm group type: Experimental
arm group label: Dose Group 4
arm group type: Experimental
arm group label: Dose Group 5
arm group type: Experimental
intervention type: Drug
intervention name: BI 1358894
description: Film-coated tablet
arm group label: Dose Group 1
arm group label: Dose Group 2
arm group label: Dose Group 3
arm group label: Dose Group 4
arm group label: Dose Group 5
intervention type: Drug
intervention name: Placebo
description: Film-coated tablet
arm group label: Dose Group 1
arm group label: Dose Group 2
arm group label: Dose Group 3
arm group label: Dose Group 4
arm group label: Dose Group 5
intervention type: Drug
intervention name: Midazolam
description: Solution for injection
arm group label: Dose Group 1
arm group label: Dose Group 2
arm group label: Dose Group 3
arm group label: Dose Group 4
arm group label: Dose Group 5
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Midazolam
sharing ipd: Undecided
ipd description: Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions:
Studies in products where Boehringer Ingelheim is not the license holder;
studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials;
Studies conducted in a single center or targeting rare diseases (because of limitations with anonymization).
Requestors can use the following link http:// trials.boehringer-ingelheim.com/ to:
find information in order to request access to clinical study data, for listed studies.
request access to clinical study documents that meet criteria, and upon a signed 'Document Sharing Agreement.