<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/NCT02211469</url>
  </required_header>
  <id_info>
    <org_study_id>IM001-001</org_study_id>
    <nct_id>NCT02211469</nct_id>
  </id_info>
  <brief_title>A Randomized, Placebo-Controlled, Double-Blind, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BMS-986104 in Healthy Male Subjects</brief_title>
  <official_title>A Randomized, Placebo-Controlled, Double-Blind, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BMS-986104 in Healthy Male Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Bristol-Myers Squibb</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective in this study is to assess if single doses of BMS-986104 that are safe,&#xD;
      tolerable, and result in sufficient lymphopenia (50% to 70% reduction in absolute lymphocyte&#xD;
      count) can be achieved without bradycardia or other adverse events in healthy male subjects.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">July 2015</completion_date>
  <primary_completion_date type="Actual">July 2015</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of all adverse events (AEs) / serious adverse events (SAEs)</measure>
    <time_frame>Up to 1 month post discharge</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean difference in ECG heart rate (HR) nadir values</measure>
    <time_frame>Up to 4 days postdose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Nadir absolute lymphocyte count (ALC) defined as the lowest ALC measured at any time after the dose</measure>
    <time_frame>Up to 4 days postdose</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability based on severity, investigator causality assessment and outcomes of all AEs (regardless of seriousness criteria), association between AEs and study drug exposure parameters, and physical examination</measure>
    <time_frame>Up to 1 month post discharge</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean difference in ECG HR values in BMS-986104-treated versus placebo-treated healthy male subjects, identifying nadir ECG HR</measure>
    <time_frame>Day -1 up to 24h and Days 1-5</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent reduction in ECG HR</measure>
    <time_frame>Day -1 up to 24h and Days 1-5</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to nadir ECG HR</measure>
    <time_frame>Day -1 up to 24h and Days 1-5</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum observed blood concentration (Cmax) of BMS-986104</measure>
    <time_frame>Up to Day 56</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of maximum observed blood concentration (Tmax) of BMS-986104</measure>
    <time_frame>Up to Day 56</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal half-life (T-HALF) of BMS-986104</measure>
    <time_frame>Up to Day 56</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the blood concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-T)] of BMS-986104</measure>
    <time_frame>Up to Day 56</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the blood concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-986104</measure>
    <time_frame>Up to Day 56</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent total clearance (CLT/F) of BMS-986104</measure>
    <time_frame>Up to Day 56</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution of terminal phase (Vz/F) of BMS-986104</measure>
    <time_frame>Up to Day 56</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Metabolite to parent AUC(INF) ratio [MR_AUC(INF)] for both BMS-986104 and BMT-019434</measure>
    <time_frame>Up to Day 56</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effects of single oral doses of BMS-986104 on the following ALC</measure>
    <time_frame>Up to 4 days postdose</time_frame>
    <description>Time to nadir ALC from time 0h (predose)&#xD;
Percent reduction in ALC from baseline to nadir</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">41</enrollment>
  <condition>Rheumatoid Arthritis</condition>
  <arm_group>
    <arm_group_label>Panel 1: BMS-986104 or Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BMS-986104 or Placebo single dose by mouth as specified</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Panel 2: BMS-986104 or Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BMS-986104 or Placebo single dose by mouth as specified</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Panel 3: BMS-986104 or Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BMS-986104 or Placebo single dose by mouth as specified</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Panel 4: BMS-986104 or Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BMS-986104 or Placebo single dose by mouth as specified</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BMS-986104</intervention_name>
    <arm_group_label>Panel 1: BMS-986104 or Placebo</arm_group_label>
    <arm_group_label>Panel 2: BMS-986104 or Placebo</arm_group_label>
    <arm_group_label>Panel 3: BMS-986104 or Placebo</arm_group_label>
    <arm_group_label>Panel 4: BMS-986104 or Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Panel 1: BMS-986104 or Placebo</arm_group_label>
    <arm_group_label>Panel 2: BMS-986104 or Placebo</arm_group_label>
    <arm_group_label>Panel 3: BMS-986104 or Placebo</arm_group_label>
    <arm_group_label>Panel 4: BMS-986104 or Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        For more information regarding BMS clinical trial participation, please visit&#xD;
        www.BMSStudyConnect.com.&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male subjects as determined by medical history, physical examination, vital&#xD;
             signs, 12-lead electrocardiogram (ECG), and clinical laboratory evaluations will be&#xD;
             eligible to participate in the study&#xD;
&#xD;
          -  Men ages 18 to 49 years, inclusive&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any acute or chronic medical illness judged to be clinically-significant by the&#xD;
             Investigator and/or Sponsor medical monitor&#xD;
&#xD;
          -  Presence of fecal occult blood at screening&#xD;
&#xD;
          -  History of prolonged occupational exposure to organic solvents or pesticides&#xD;
&#xD;
          -  History of vitamin B12 deficiency and/or achlorhydria; or a vitamin B12 level at&#xD;
             screening &lt;lower limit of normal (LLN), confirmed by repeat test&#xD;
&#xD;
          -  History of Guillain-Barré Syndrome&#xD;
&#xD;
          -  Past or current history of central or peripheral neuropathies, or past or current&#xD;
             symptoms of sustained or recurrent paresthesias (tingling), numbness, or neuropathic&#xD;
             pain (burning, aching or stabbing) in any extremities. Note: Experiencing an extremity&#xD;
             &quot;falling asleep&quot; occasionally is not be exclusionary&#xD;
&#xD;
          -  Clinically significant abnormality in the neurological exam at baseline (predose)&#xD;
&#xD;
          -  Clinically significant nerve electrophysiology abnormalities at baseline (predose)&#xD;
&#xD;
          -  Any history of testicular or epididymal disease/disorder&#xD;
&#xD;
          -  Clinically significant abnormality on ophthalmologic exam or any findings suggesting&#xD;
             an increased risk of macular edema at baseline (predose)&#xD;
&#xD;
          -  History of hypothyroidism or carpal tunnel syndrome&#xD;
&#xD;
          -  Subjects with history of diabetes mellitus&#xD;
&#xD;
          -  Subjects with history of any type of heart disease, including ischemia, infarction,&#xD;
             arrhythmias, hypertension, atrioventricular block of any degree, bradycardia, syncope,&#xD;
             clinically significant ECG abnormalities, or any congenital heart disease&#xD;
&#xD;
          -  Subjects with any acute or chronic bacterial, fungal or viral infection within the&#xD;
             last 3 months prior to screening, as well as any febrile illness of unknown origin&#xD;
             within 14 days of screening&#xD;
&#xD;
          -  Subjects who have received any live vaccines within 1 month of study drug&#xD;
             administration or who plan to have a live vaccine at any time during the study&#xD;
&#xD;
          -  Positive test for tuberculosis at screening (QuantiFERON® GOLD)&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>49 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bristol-Myers Squibb</last_name>
    <role>Study Director</role>
    <affiliation>Bristol-Myers Squibb</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Covance Clinical Research Unit, Inc.</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53704</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.bms.com/studyconnect/Pages/home.aspx</url>
    <description>BMS clinical trial educational resource</description>
  </link>
  <verification_date>April 2015</verification_date>
  <study_first_submitted>August 6, 2014</study_first_submitted>
  <study_first_submitted_qc>August 6, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 7, 2014</study_first_posted>
  <last_update_submitted>September 16, 2015</last_update_submitted>
  <last_update_submitted_qc>September 16, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 18, 2015</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>Arthritis</mesh_term>
    <mesh_term>Arthritis, Rheumatoid</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/NCT02211469
org study id: IM001-001
nct id: NCT02211469
lead sponsor: 
has dmc: No
The primary objective in this study is to assess if single doses of BMS-986104 that are safe,
      tolerable, and result in sufficient lymphopenia (50% to 70% reduction in absolute lymphocyte
      count) can be achieved without bradycardia or other adverse events in healthy male subjects.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Incidence of all adverse events (AEs) / serious adverse events (SAEs)
time frame: Up to 1 month post discharge
measure: Mean difference in ECG heart rate (HR) nadir values
time frame: Up to 4 days postdose
measure: Nadir absolute lymphocyte count (ALC) defined as the lowest ALC measured at any time after the dose
time frame: Up to 4 days postdose
measure: Safety and tolerability based on severity, investigator causality assessment and outcomes of all AEs (regardless of seriousness criteria), association between AEs and study drug exposure parameters, and physical examination
time frame: Up to 1 month post discharge
measure: Mean difference in ECG HR values in BMS-986104-treated versus placebo-treated healthy male subjects, identifying nadir ECG HR
time frame: Day -1 up to 24h and Days 1-5
measure: Percent reduction in ECG HR
time frame: Day -1 up to 24h and Days 1-5
measure: Time to nadir ECG HR
time frame: Day -1 up to 24h and Days 1-5
measure: Maximum observed blood concentration (Cmax) of BMS-986104
time frame: Up to Day 56
measure: Time of maximum observed blood concentration (Tmax) of BMS-986104
time frame: Up to Day 56
measure: Terminal half-life (T-HALF) of BMS-986104
time frame: Up to Day 56
measure: Area under the blood concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-T)] of BMS-986104
time frame: Up to Day 56
measure: Area under the blood concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-986104
time frame: Up to Day 56
measure: Apparent total clearance (CLT/F) of BMS-986104
time frame: Up to Day 56
measure: Apparent volume of distribution of terminal phase (Vz/F) of BMS-986104
time frame: Up to Day 56
measure: Metabolite to parent AUC(INF) ratio [MR_AUC(INF)] for both BMS-986104 and BMT-019434
time frame: Up to Day 56
measure: Effects of single oral doses of BMS-986104 on the following ALC
time frame: Up to 4 days postdose
description: Time to nadir ALC from time 0h (predose)
Percent reduction in ALC from baseline to nadir
arm group label: Panel 1: BMS-986104 or Placebo
arm group type: Experimental
description: BMS-986104 or Placebo single dose by mouth as specified
arm group label: Panel 2: BMS-986104 or Placebo
arm group type: Experimental
description: BMS-986104 or Placebo single dose by mouth as specified
arm group label: Panel 3: BMS-986104 or Placebo
arm group type: Experimental
description: BMS-986104 or Placebo single dose by mouth as specified
arm group label: Panel 4: BMS-986104 or Placebo
arm group type: Experimental
description: BMS-986104 or Placebo single dose by mouth as specified
intervention type: Drug
intervention name: BMS-986104
arm group label: Panel 1: BMS-986104 or Placebo
arm group label: Panel 2: BMS-986104 or Placebo
arm group label: Panel 3: BMS-986104 or Placebo
arm group label: Panel 4: BMS-986104 or Placebo
intervention type: Drug
intervention name: Placebo
arm group label: Panel 1: BMS-986104 or Placebo
arm group label: Panel 2: BMS-986104 or Placebo
arm group label: Panel 3: BMS-986104 or Placebo
arm group label: Panel 4: BMS-986104 or Placebo
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 49 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Bristol-Myers Squibb
role: Study Director
affiliation: Bristol-Myers Squibb
facility: 
country: United States
url: http://www.bms.com/studyconnect/Pages/home.aspx
description: BMS clinical trial educational resource
responsible party type: Sponsor
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid