<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/NCT03281122</url>
  </required_header>
  <id_info>
    <org_study_id>CV016-007</org_study_id>
    <nct_id>NCT03281122</nct_id>
  </id_info>
  <brief_title>A Study of BMS-986224 in Healthy Subjects and Heart Failure Patients With Reduced Ejection Fraction</brief_title>
  <official_title>A Randomized, Double-Blinded, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BMS-986224 in Healthy Subjects and Chronic Heart Failure Patients With Reduced Ejection Fraction</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>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is test the safety and tolerability of BMS-986224 and its effects&#xD;
      on the body in healthy subjects and subjects with chronic heart failure with reduced ejection&#xD;
      fraction&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Business objectives have changed&#xD;
  </why_stopped>
  <start_date type="Actual">September 22, 2017</start_date>
  <completion_date type="Actual">April 17, 2019</completion_date>
  <primary_completion_date type="Actual">April 17, 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>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Serious Adverse Events (SAEs)</measure>
    <time_frame>Up to one month</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Adverse Events (AEs)</measure>
    <time_frame>Up to one month</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of deaths</measure>
    <time_frame>Up to one month</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum observed plasma concentration (Cmax)</measure>
    <time_frame>Up to one month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of maximum observed plasma concentration (Tmax)</measure>
    <time_frame>Up to one month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal elimination half-life (T-HALF)</measure>
    <time_frame>Up to one month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-T)]</measure>
    <time_frame>Up to one month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration-time curve from time zero extrapoloated [AUC(INF)]</measure>
    <time_frame>Up to one month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve in one dosing interval [AUC(TAU)]</measure>
    <time_frame>Up to one month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation ratio: ratio of Cmax following last dose to Cmax following first dose (ARcmax)</measure>
    <time_frame>Up to one month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation ratio: ratio of AUC(TAU) following last dose to AUC(TAU) following first dose (ARtau)</measure>
    <time_frame>Up to one month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal elimination rate constant (kel)</measure>
    <time_frame>Up to one month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent oral clearance, calculated as dose/AUC(INF) for single dose or dose/AUC(TAU) for multiple dose</measure>
    <time_frame>Up to one month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution at terminal phase (Vz/F)</measure>
    <time_frame>Up to one month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative urinary excretion (of the unchanged drug) over one dosing interval [Ae(TAU)]</measure>
    <time_frame>Up to one month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative urinary excretion (of the unchanged drug) [Aet]</measure>
    <time_frame>Up to one month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal clearance (CLr)</measure>
    <time_frame>Up to one month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Amount excreted unchanged (%) [UR%]</measure>
    <time_frame>Up to one month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ratio of Metabolite Cmax to Parent Cmax, corrected for molecular weight (MR_Cmax)</measure>
    <time_frame>Up to one month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ratio of Metabolite AUC(INF) to Parent AUC(INF), corrected for molecular weight</measure>
    <time_frame>Up to one month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ratio of Metabolite AUC(0-T) to Parent AUC(0-T), corrected for molecular weight [MR_AUC(0-T)]</measure>
    <time_frame>Up to one month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ratio of Metabolite AUC(TAU) to Parent AUC(TAU), corrected for molecular weight [MR_AUC(TAU)]</measure>
    <time_frame>Up to one month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Drug-drug interaction (DDI) assessment</measure>
    <time_frame>Up to one month</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">199</enrollment>
  <condition>Heart Failure</condition>
  <arm_group>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Specified dose on specified days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Specified dose on specified days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Specified dose on specified days</description>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_label>Arm B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BMS-986224</intervention_name>
    <description>Specified dose on specified days</description>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_label>Arm B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        For more information regarding Bristol-Myers Squibb Clinical Trial participation, please&#xD;
        visit www.BMSStudyConnect.com&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
        Healthy Subjects (Part A and B)&#xD;
&#xD;
          -  Healthy subjects, as determined by no clinically significant deviations in medical&#xD;
             history, physical examination, ECGs, vital signs, and clinical laboratory&#xD;
             determinations&#xD;
&#xD;
          -  Subjects must be willing and able to complete all study-specific procedures and visits&#xD;
&#xD;
          -  Additional criterion for Japanese subjects in Groups BJ1 to BJ3: Subjects must be&#xD;
             first generation Japanese (born in Japan and not living outside of Japan for &gt; 10&#xD;
             years, and both parents are ethnically Japanese)&#xD;
&#xD;
        Heart Failure Patients (Part C)&#xD;
&#xD;
          -  Left ventricular EF &lt;45% and &gt;25%, as assessed by cardiac MRI within 3 months of first&#xD;
             dose of study drug; or left ventricular EF &lt;40% and &gt;25% as assessed by echocardiogram&#xD;
             at Screening or within 3 months of first dose of study drug; left ventricular EF&#xD;
&#xD;
          -  Heart failure is considered to be stable at the discretion of the Investigator (i.e.,&#xD;
             no acute cardiovascular [CV] events or hospitalization (including emergency room&#xD;
             visits) for CV causes within 3 months of first dose of study drug&#xD;
&#xD;
          -  Regular sinus rhythm at Screening and no history of atrial fibrillation in the past 12&#xD;
             months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Healthy Subjects (Part A and B)&#xD;
&#xD;
          -  Major surgery within 4 weeks of (first) study treatment administration&#xD;
&#xD;
          -  Inability to be venipunctured and/or tolerate venous access&#xD;
&#xD;
          -  Subjects who have smoked or used smoking cessation or nicotine containing products&#xD;
             (including, but not limited, to e-cigarettes, pipes, cigars, chewing tobacco, nicotine&#xD;
             patches, nicotine lozenges, or nicotine gum, varenicline, bupropion) within 6 months&#xD;
             of the first dose of study drug&#xD;
&#xD;
        Heart Failure Patients (Part C)&#xD;
&#xD;
          -  Current or recent (within 3 months of study treatment administration) gastrointestinal&#xD;
             disease that could affect absorption&#xD;
&#xD;
          -  Major surgery within 4 weeks of (first) study treatment administration&#xD;
&#xD;
          -  Inability to be venipunctured and/or tolerate venous access&#xD;
&#xD;
        Other protocol defined inclusion/exclusion criteria could apply&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 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>Vseobecna Fakultni Nemocnice v Praze</name>
      <address>
        <city>Praha 2</city>
        <zip>12808</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Krajska zdravotni - Masarykova nemocnice v Usti nad Labem</name>
      <address>
        <city>Usti nad Labem</city>
        <zip>401 13</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Deventer Ziekenhuis</name>
      <address>
        <city>Deventer</city>
        <zip>7416 SE</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitair Medisch Centrum Groningen</name>
      <address>
        <city>Groningen</city>
        <zip>9713 GZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PRA Health Sciences - Groningen</name>
      <address>
        <city>Groningen</city>
        <zip>9728 NZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spaarne Gasthuis - Haarlem-Zuid</name>
      <address>
        <city>Haarlem</city>
        <zip>2035 RC</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>D &amp; A Research and Genetics</name>
      <address>
        <city>Sneek</city>
        <zip>8601 ZR</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samodzielny Publiczny Szpital Kliniczny Number 4 w Lublinie</name>
      <address>
        <city>Lublin</city>
        <zip>20-954</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>4th Wojskowy Szpital Kliniczny z Poliklinika Samodzielny Publiczny Zaklad Opieki Zdrowotnej</name>
      <address>
        <city>Wroclaw</city>
        <zip>50-981</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Ramon Y Cajal</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Fundacion Jimenez Diaz</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Complejo Hospitalario Universitario de Santiago</name>
      <address>
        <city>Santiago de Compostela</city>
        <zip>15706</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinico Universitario de Valencia</name>
      <address>
        <city>Valencia</city>
        <zip>46010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Alvaro Cunqueiro</name>
      <address>
        <city>Vigo</city>
        <zip>36312</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals Birmingham NHS Foundation Trust</name>
      <address>
        <city>Birmingham</city>
        <zip>B15 2TH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NHS Tayside</name>
      <address>
        <city>Dundee</city>
        <zip>DD1 9SY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Edinburgh</name>
      <address>
        <city>Edinburgh</city>
        <zip>EH16 4SB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Richmond Pharmacology</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Czechia</country>
    <country>Netherlands</country>
    <country>Poland</country>
    <country>Spain</country>
    <country>United Kingdom</country>
  </location_countries>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <link>
    <url>https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html</url>
    <description>BMS Clinical Trial Information</description>
  </link>
  <link>
    <url>https://www.bmsstudyconnect.com/s/US/English/USenHome</url>
    <description>BMS Clinical Trial Patient Recruiting</description>
  </link>
  <link>
    <url>https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm</url>
    <description>FDA Safety Alerts and Recalls</description>
  </link>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>September 11, 2017</study_first_submitted>
  <study_first_submitted_qc>September 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 13, 2017</study_first_posted>
  <last_update_submitted>February 24, 2021</last_update_submitted>
  <last_update_submitted_qc>February 24, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 25, 2021</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>Heart Failure</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/NCT03281122
org study id: CV016-007
nct id: NCT03281122
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The purpose of this study is test the safety and tolerability of BMS-986224 and its effects
      on the body in healthy subjects and subjects with chronic heart failure with reduced ejection
      fraction
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Number of Serious Adverse Events (SAEs)
time frame: Up to one month
measure: Number of Adverse Events (AEs)
time frame: Up to one month
measure: Number of deaths
time frame: Up to one month
measure: Maximum observed plasma concentration (Cmax)
time frame: Up to one month
measure: Time of maximum observed plasma concentration (Tmax)
time frame: Up to one month
measure: Terminal elimination half-life (T-HALF)
time frame: Up to one month
measure: Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-T)]
time frame: Up to one month
measure: Area under the plasma concentration-time curve from time zero extrapoloated [AUC(INF)]
time frame: Up to one month
measure: Area under the concentration-time curve in one dosing interval [AUC(TAU)]
time frame: Up to one month
measure: Accumulation ratio: ratio of Cmax following last dose to Cmax following first dose (ARcmax)
time frame: Up to one month
measure: Accumulation ratio: ratio of AUC(TAU) following last dose to AUC(TAU) following first dose (ARtau)
time frame: Up to one month
measure: Terminal elimination rate constant (kel)
time frame: Up to one month
measure: Apparent oral clearance, calculated as dose/AUC(INF) for single dose or dose/AUC(TAU) for multiple dose
time frame: Up to one month
measure: Apparent volume of distribution at terminal phase (Vz/F)
time frame: Up to one month
measure: Cumulative urinary excretion (of the unchanged drug) over one dosing interval [Ae(TAU)]
time frame: Up to one month
measure: Cumulative urinary excretion (of the unchanged drug) [Aet]
time frame: Up to one month
measure: Renal clearance (CLr)
time frame: Up to one month
measure: Amount excreted unchanged (%) [UR%]
time frame: Up to one month
measure: Ratio of Metabolite Cmax to Parent Cmax, corrected for molecular weight (MR_Cmax)
time frame: Up to one month
measure: Ratio of Metabolite AUC(INF) to Parent AUC(INF), corrected for molecular weight
time frame: Up to one month
measure: Ratio of Metabolite AUC(0-T) to Parent AUC(0-T), corrected for molecular weight [MR_AUC(0-T)]
time frame: Up to one month
measure: Ratio of Metabolite AUC(TAU) to Parent AUC(TAU), corrected for molecular weight [MR_AUC(TAU)]
time frame: Up to one month
measure: Drug-drug interaction (DDI) assessment
time frame: Up to one month
arm group label: Arm A
arm group type: Experimental
description: Specified dose on specified days
arm group label: Arm B
arm group type: Placebo Comparator
description: Specified dose on specified days
intervention type: Drug
intervention name: Placebo
description: Specified dose on specified days
arm group label: Arm A
arm group label: Arm B
intervention type: Drug
intervention name: BMS-986224
description: Specified dose on specified days
arm group label: Arm A
arm group label: Arm B
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Bristol-Myers Squibb
role: Study Director
affiliation: Bristol-Myers Squibb
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Czechia
country: Netherlands
country: Poland
country: Spain
country: United Kingdom
country: United States
url: https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
description: BMS Clinical Trial Information
url: https://www.bmsstudyconnect.com/s/US/English/USenHome
description: BMS Clinical Trial Patient Recruiting
url: https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm
description: FDA Safety Alerts and Recalls
responsible party type: Sponsor
mesh term: Heart Failure