<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/NCT03276728</url>
  </required_header>
  <id_info>
    <org_study_id>20150183</org_study_id>
    <secondary_id>2017-002940-34</secondary_id>
    <nct_id>NCT03276728</nct_id>
  </id_info>
  <brief_title>Study to Evaluate the Safety and Tolerability of AMG 986 in Healthy Volunteers and Heart Failure Patients</brief_title>
  <official_title>A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 986 in Healthy Subjects and Heart Failure Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Amgen</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Amgen</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate the safety and tolerability of ascending single (Part A) and ascending multiple&#xD;
      (Part B) doses of AMG 986 in healthy adults and of ascending multiple oral doses of AMG 986&#xD;
      in heart failure patients (Part C).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a randomized, placebo-controlled, double-blind, single day ascending dose&#xD;
      (SDAD) study (Part A), a multiple daily ascending dose (MDAD) study (Part B), in healthy&#xD;
      adults, and a MDAD study (Part C) in heart failure patients. In Parts A and B of the study,&#xD;
      healthy volunteers will receive AMG 986 by continuous IV infusion or by oral administration&#xD;
      in a fasted state. IV Infusions will be divided into an initial loading dose (LD) for the&#xD;
      first hour followed immediately by a maintenance dose (MD).&#xD;
&#xD;
      In Part C of the study, patients with heart failure and either reduced (HFrEF) or preserved&#xD;
      (HFpEF) ejection fraction will receive MDAD of AMG 986 or matching placebo once daily by oral&#xD;
      administration for 21 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Terminated (Decision by the Sponsor. The study was not terminated due to a safety reason.)&#xD;
  </why_stopped>
  <start_date type="Actual">August 12, 2016</start_date>
  <completion_date type="Actual">April 18, 2019</completion_date>
  <primary_completion_date type="Actual">April 18, 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>
    <intervention_model_description>Double-blind, placebo-controlled</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>Double-blinded</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Participants With Treatment Emergent Adverse Events (TEAE)</measure>
    <time_frame>Part A: Day 1 up to Day 31 Part B: Day 1 up to Day 37 Part C: Day 1 up to Day 51</time_frame>
    <description>An adverse event is defined as any untoward medical occurrence in a clinical trial subject. The event does not necessarily have a causal relationship with study treatment. Events categorized as TEAEs started on or after first dose of study drug and include up to 30 days after the last dose.&#xD;
A serious AE is an AE that met one or more of the following criteria:&#xD;
Death&#xD;
Life-threatening&#xD;
Required inpatient hospitalization or prolongation of an existing hospitalization&#xD;
Resulted in persistent or significant disability/incapacity&#xD;
A congenital anomaly/birth defect&#xD;
Important medical events that required medical or surgical intervention to prevent one of the outcomes above.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Left Ventricular Ejection Fraction by Visit for Part C Heart Failure With Reduced Ejection Fraction (HFrEF) Cohort</measure>
    <time_frame>Baseline (Day 1 predose), Day 8, Day 15, Day 21, Day 30</time_frame>
    <description>Heart failure (HF) refers to a clinical condition in which the cardiac output is insufficient to meet the metabolic needs of body organs and is marked by cardiac systolic and/or diastolic dysfunction. Heart failure with predominantly systolic dysfunction, which is identifiable as decreased contraction, is more aptly described as heart failure with reduced ejection fraction (HFrEF). Ejection fraction is a measurement, expressed as a percentage, of how much blood the left ventricle pumps out with each contraction and is measured by echocardiogram.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stroke Volume (Method of Disks, Volumetric Assessment) by Visit for Part C Heart Failure With Reduced Ejection Fraction (HFrEF) Cohort</measure>
    <time_frame>Baseline (Day 1 predose), Day 8, Day 15, Day 21, Day 30</time_frame>
    <description>Stroke volume is the amount of blood pumped by the left ventricle of the heart in one contraction reported by volumetric method of disks (MoD) assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stroke Volume (Left Ventricular Outflow Tract Using Doppler Assessment) by Visit for Part C Heart Failure With Reduced Ejection Fraction (HFrEF) Cohort</measure>
    <time_frame>Baseline (Day 1 predose), Day 8, Day 15, Day 21, Day 30</time_frame>
    <description>Stroke volume is the amount of blood pumped by the left ventricle of the heart in one contraction as measured using left ventricular outflow tract (LVOT) Doppler assessment.</description>
  </secondary_outcome>
  <number_of_arms>8</number_of_arms>
  <enrollment type="Actual">182</enrollment>
  <condition>Heart Failure</condition>
  <condition>Healthy Volunteer</condition>
  <arm_group>
    <arm_group_label>Part A: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Healthy participants were administered placebo either intravenously (IV) or by mouth (PO) to match the 5 IV cohorts and 6 PO cohorts of AMG 986.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part A: AMG 986</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy participants were administered a single dose of AMG 986 either IV or PO. The 5 IV cohorts started at a 0.5 mg loading dose over one hour up to to the Cohort 5 IV dosage consisting of a 60 mg loading dose over 1 hour and a 360 mg maintenance dose lasting 23 hours. The 6 PO cohorts started at a single 5 mg dose up to the Cohort 6 PO dose of 650 mg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Healthy participants were administered placebo either IV for 4 consecutive days or PO for 7 days to match the 2 IV cohorts and 6 PO cohorts of AMG 986.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B: AMG 986</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy participants were administered AMG 986 either IV or PO. IV cohort 1 was administered a loading dose of 6 mg over one hour followed by maintenance doses of 36 mg lasting 23 hours on Day 1 and 38 mg lasting 24 hours on Days 2-4. IV cohort 2 was administered a loading dose of 60 mg over one hour followed by maintenance doses of 360 mg lasting 23 hours on Day 1 and 376 mg lasting 24 hours on Days 2-4. The 6 PO cohorts started at 5 mg for 7 days up to Cohort 6 PO dose of 650 mg for 7 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part C: HFrEF Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO placebo tablet daily from Days 1-21.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part C: HFpEF Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants with heart failure with preserved ejection fraction (HFpEF) were administered a single PO placebo tablet daily from Days 1-21.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part C: HFrEF AMG 986</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO AMG 986 tablet daily from Days 1-21 in ascending doses of 10 mg for Days 1-7, 30 mg for Days 8-14 and 100 mg for days 15-21.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part C: HFpEF AMG 986</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants with heart failure with preserved ejection fraction (HFpEF) were administered a single PO AMG 986 tablet daily from Days 1-21 in ascending doses of 10 mg for Days 1-7, 30 mg for Days 8-14 and 100 mg for days 15-21.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AMG 986 IV</intervention_name>
    <description>AMG 986 solution for infusion</description>
    <arm_group_label>Part A: AMG 986</arm_group_label>
    <arm_group_label>Part B: AMG 986</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AMG 986 PO</intervention_name>
    <description>AMG 986 tablets for oral (PO) administration</description>
    <arm_group_label>Part A: AMG 986</arm_group_label>
    <arm_group_label>Part B: AMG 986</arm_group_label>
    <arm_group_label>Part C: HFpEF AMG 986</arm_group_label>
    <arm_group_label>Part C: HFrEF AMG 986</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo PO</intervention_name>
    <description>Matching placebo tablets for oral administration</description>
    <arm_group_label>Part A: Placebo</arm_group_label>
    <arm_group_label>Part B: Placebo</arm_group_label>
    <arm_group_label>Part C: HFpEF Placebo</arm_group_label>
    <arm_group_label>Part C: HFrEF Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo IV</intervention_name>
    <description>Matching placebo solution for infusion</description>
    <arm_group_label>Part A: Placebo</arm_group_label>
    <arm_group_label>Part B: Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          -  Subject has provided informed consent prior to initiation of any study-specific&#xD;
             activities/procedures.&#xD;
&#xD;
          -  Male and female subjects ≥ 18 to ≤ 55 years old with no history or evidence of&#xD;
             clinically relevant medical disorders as determined by the investigator and the Amgen&#xD;
             physician (Parts A and B only)&#xD;
&#xD;
          -  Body mass index (BMI) between 18 and 35 kg/m^2, inclusive, at screening.&#xD;
&#xD;
          -  Physical examination including vital signs, clinical laboratory values, and&#xD;
             electrocardiograms (ECGs) are clinically acceptable to the investigator. Abnormal&#xD;
             findings for healthy volunteers and unexpected findings for heart failure patient&#xD;
             subjects will be discussed with Amgen prior to study enrollment.&#xD;
&#xD;
          -  Women must be of non-reproductive potential (ie, postmenopausal)&#xD;
&#xD;
          -  Men must agree to practice an acceptable method of effective birth control while on&#xD;
             study through 11 weeks after receiving the last dose of investigational product (AMG&#xD;
             986 or placebo). Acceptable methods of effective birth control include sexual&#xD;
             abstinence; vasectomy and testing that shows there are no sperm in the semen; or a&#xD;
             condom with spermicide (men) in combination with barrier methods (diaphragm, cervical&#xD;
             cap or cervical sponge), hormonal birth control or IUS (women).&#xD;
&#xD;
          -  Men must be willing to abstain from sperm donation while on study through 11 weeks&#xD;
             after receiving the last dose of investigational product (AMG 986 or placebo).&#xD;
&#xD;
          -  This inclusion criterion only applies to Parts B and C cohorts. Before inclusion in&#xD;
             the study, subjects will undergo a screening echocardiogram to ensure that the&#xD;
             following parameters can be accurately measured: left ventricular end-systolic and&#xD;
             end-diastolic volumes, left atrial end-systolic and end-diastolic volumes, ejection&#xD;
             fraction, fraction shortening, and end-systolic septal and posterior wall thickness.&#xD;
&#xD;
        For Part C&#xD;
&#xD;
        Additional Inclusion Criteria for HFrEF Patients:&#xD;
&#xD;
          -  Subject must be of age 18 to 85 years, have a diagnosis of HF confirmed by medical&#xD;
             records for ≥ 3 months, and be in stable condition for at least 4 weeks.&#xD;
&#xD;
          -  Left ventricular ejection fraction (LVEF) ≤ 40% confirmed by echocardiogram,&#xD;
             radionuclide ventriculography, cardiac magnetic resonance imaging, or contrast&#xD;
             ventriculography within 12 months prior to randomization.&#xD;
&#xD;
          -  New York Heart Association (NYHA) class II or III at screening&#xD;
&#xD;
          -  Sinus rhythm&#xD;
&#xD;
          -  N-terminal pro b-type natriuretic peptide (NT-proBNP) level ≥ 250 pg/ml&#xD;
&#xD;
          -  Patients will be treated with stable, optimal pharmacological therapy for a minimum of&#xD;
             4 weeks prior to randomization. Treatment of HFrEF includes at least beta-blockers&#xD;
             (carvedilol, metoprolol succinate or bisoprolol) and a RAAS inhibitor (ACEi, ARB or&#xD;
             sacubitril/valsartan).&#xD;
&#xD;
        Additional Inclusion Criteria for HFpEF patients:&#xD;
&#xD;
          -  Subject must be of age of 18 to 85 years, have a diagnosis of HF confirmed by medical&#xD;
             records for ≥ 3 months, and be in stable condition for at least 4 weeks.&#xD;
&#xD;
          -  LVEF ≥ 50% confirmed by echocardiogram, radionuclide ventriculography, cardiac&#xD;
             magnetic resonance imaging, or contrast ventriculography within 12 months prior to&#xD;
             randomization.&#xD;
&#xD;
          -  LVEF never ≤ 40% in the past&#xD;
&#xD;
          -  NYHA class II or III at screening&#xD;
&#xD;
          -  Sinus rhythm&#xD;
&#xD;
          -  NT-proBNP level ≥ 250 pg/ml&#xD;
&#xD;
          -  Patients will be treated with stable, optimal pharmacological therapy for a minimum of&#xD;
             4 weeks prior to randomization. Treatment of HFpEF includes at least a daily dose of&#xD;
             diuretics equivalent to furosemide 40 mg.&#xD;
&#xD;
          -  For subjects in Parts A, B and C: Women must have negative results for both the&#xD;
             screening (serum) and day -1 (serum or urine) pregnancy tests&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  Currently receiving treatment in another investigational device or drug study, or less&#xD;
             than 30 days or 5 half-lives (whichever is longer), since ending treatment on another&#xD;
             investigational device or drug study(s) prior to receiving the first dose of&#xD;
             investigational product (AMG 986 or placebo).&#xD;
&#xD;
          -  Female subjects who are lactating/breastfeeding or who plan to breastfeed while on&#xD;
             study through 11 weeks after receiving the last dose of investigational product (AMG&#xD;
             986 or placebo).&#xD;
&#xD;
          -  Male subjects with partners who are pregnant or planning to become pregnant while the&#xD;
             subject is on study through 11 weeks after receiving the last dose of investigational&#xD;
             product (AMG 986 or placebo).&#xD;
&#xD;
          -  Female subjects of reproductive potential.&#xD;
&#xD;
          -  Subjects in Parts A and B of the study: estimated glomerular filtration rate (eGFR)&#xD;
             within the screening period of less than 60 mL/min/1.73m^2 as calculated using the&#xD;
             estimated Modification of Diet in Renal Disease (MDRD) formula.&#xD;
&#xD;
          -  Current or prior malignancy within 5 years of randomization, with the exception of&#xD;
             non-melanoma skin cancers, cervical or breast ductal carcinoma in situ, and&#xD;
             adenocarcinoma of the prostate Stage I or IIa (defined as T1, T2a or T2b, N0, M0 with&#xD;
             documented serum prostate-specific antigen (PSA) &lt; 20 ng/mL and Gleason score ≤ 7) per&#xD;
             the American Joint Committee on Cancer (AJCC) primary tumor, regional lymph nodes, and&#xD;
             distant metastasis system.&#xD;
&#xD;
          -  Positive results for human immunodeficiency virus (HIV), antibodies, hepatitis B&#xD;
             surface antigen (HBsAg), or hepatitis C antibodies (HepCAb).&#xD;
&#xD;
          -  Subject has known sensitivity to any of the products or components to be administered&#xD;
             during dosing.&#xD;
&#xD;
          -  Subject likely to not be available to complete all protocol required study visits or&#xD;
             procedures, and/or to comply with all required study procedures to the best of the&#xD;
             subject and investigator's knowledge.&#xD;
&#xD;
          -  History or evidence of any other clinically significant disorder, condition or disease&#xD;
             with the exception of those outlined above that, in the opinion of the investigator or&#xD;
             Amgen physician, if consulted, would pose a risk to subject safety or interfere with&#xD;
             the study evaluation, procedures or completion.&#xD;
&#xD;
          -  Subject previously has entered this study or has been previously exposed to AMG 986.&#xD;
&#xD;
          -  Concurrent or prior use of strong CYP3A4 inhibitors within 14 days of study Day 1,&#xD;
             including (not limited to): macrolide antibiotics (eg, clarithromycin, telithromycin),&#xD;
             antifungals (eg, itraconazole, voriconazole), antivirals (eg, ritonavir, saquinavir,&#xD;
             indinavir, nelfinavir), nefazodone.&#xD;
&#xD;
          -  Concurrent or prior ingestion of grapefruit or grapefruit products and other foods&#xD;
             that are known to inhibit CYP3A4 within 7 days of study Day 1.&#xD;
&#xD;
          -  Concurrent or prior use of strong CYP3A4 inducers within 28 days of study Day 1,&#xD;
             Including (not limited to): phenytoin, carbamazepine, rifampin, rifabutin, rifapentin,&#xD;
             phenobarbital. Subjects should also not take St John's Wort.&#xD;
&#xD;
          -  Concurrent or prior use of strong P-glycoprotein inhibitors within 28 days of study&#xD;
             Day 1, including (not limited to): elacridar and valspodar.&#xD;
&#xD;
          -  All herbal supplements, vitamins, and nutritional supplements taken within the last 30&#xD;
             days prior to dosing on Day 1 (and continued use, if appropriate), must be reviewed&#xD;
             and approved by the PI and Amgen Medical Monitor.&#xD;
&#xD;
          -  For subjects enrolled under Amendments 1-6, inclusive: QTc &gt; 450 msec or&#xD;
             history/evidence of long QT syndrome.&#xD;
&#xD;
          -  Planned elective surgery within 30 days of study completion or before return of red&#xD;
             blood cell parameters to normal values.&#xD;
&#xD;
          -  Blood donation ≥ 500 mL within 60 days of Day 1.&#xD;
&#xD;
          -  Systolic blood pressure &gt; 150 mmHg or &lt; 90 mmHg, or diastolic blood pressure &gt; 95 mmHg&#xD;
             or &lt; 60 mmHg, assessed on 2 separate occasions prior to enrollment (Parts A and B&#xD;
             only).&#xD;
&#xD;
          -  Heart rate ≥ 100 beats per minute after 5 minutes of rest or an untreated symptomatic&#xD;
             bradyarrhythmia within 1 month prior to enrollment.&#xD;
&#xD;
          -  For Parts A and B: Troponin I at screening &gt; upper limit of normal (ULN).&#xD;
&#xD;
          -  In the opinion of the Investigator, a condition that compromises the ability of the&#xD;
             subject to give written informed consent or to comply with study procedures.&#xD;
&#xD;
          -  Unwilling or unable to abstain from nicotine or tobacco containing products (including&#xD;
             but not limited to: snuff, chewing tobacco, cigars, cigarettes, pipes, or nicotine&#xD;
             patches) throughout the screening period and for the duration of the study.&#xD;
&#xD;
          -  Subjects who are unwilling or unable to limit alcohol consumption to 1 units/day (1&#xD;
             unit = 1 drink and 1 drink is equivalent to 12 ounces of regular beer, 8 to 9 ounces&#xD;
             of malt liquor, 5 ounces of wine or 1.5 ounces of 80 proof distilled spirits).&#xD;
&#xD;
          -  Subjects with a positive urine drug screen or alcohol breath test.&#xD;
&#xD;
          -  Known history of drug or alcohol abuse.&#xD;
&#xD;
          -  Concurrent use of phosphodiesterase 5 (PDE5) inhibitors including (not limited to)&#xD;
             avanafil, sildenafil, tadalafil, vardenafil.&#xD;
&#xD;
          -  Concurrent use of vasodilators by healthy subjects in Parts A and B that could in the&#xD;
             opinion of the investigator potentially lead to a drop in blood pressure in&#xD;
             combination with investigational product.&#xD;
&#xD;
          -  Severe uncorrected valvular heart disease, or hypertrophic obstructive cardiomyopathy,&#xD;
             active myocarditis, constrictive pericarditis, or clinically significant congenital&#xD;
             heart disease.&#xD;
&#xD;
          -  For subjects in Part C of the study: eGFR within the screening period of less than 30&#xD;
             mL/min/1.732m^2 as calculated using the MDRD formula.&#xD;
&#xD;
          -  For subjects in Part C of the study: Systolic blood pressure &gt; 160 mmHg or &lt; 100 mmHg,&#xD;
             or diastolic blood pressure &gt; 110 mmHg or &lt; 60 mmHg, assessed on 2 separate occasions&#xD;
             prior to enrollment.&#xD;
&#xD;
          -  For subjects in Part C of the study: troponin I &gt; ULN if there is also evidence of an&#xD;
             acute cardiovascular event.&#xD;
&#xD;
          -  For subjects enrolled in Part C under Amendment 7: QTc &gt; 500 msec or history/evidence&#xD;
             of long QT syndrome.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>MD</last_name>
    <role>Study Director</role>
    <affiliation>Amgen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Anaheim</city>
        <state>California</state>
        <zip>92801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tustin</city>
        <state>California</state>
        <zip>92780</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Metairie</city>
        <state>Louisiana</state>
        <zip>70006</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55415</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89148</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Auchenflower</city>
        <state>Queensland</state>
        <zip>4066</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bundaberg</city>
        <state>Queensland</state>
        <zip>4670</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Leabrook</city>
        <state>South Australia</state>
        <zip>5068</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Berwick</city>
        <state>Victoria</state>
        <zip>3806</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bundoora</city>
        <state>Victoria</state>
        <zip>3083</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sherbrooke</city>
        <state>Quebec</state>
        <zip>J1G 2E8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Nantes Cedex 1</city>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Rennes Cedex 9</city>
        <zip>35033</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Toulouse Cedex 9</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bad Neuheim</city>
        <zip>61231</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Berlin</city>
        <zip>13353</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Groningen</city>
        <zip>9713 GZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Christchurch</city>
        <zip>8011</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Jozefow</city>
        <zip>05-410</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Wroclaw</city>
        <zip>51-162</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Singapore</city>
        <zip>169609</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Canada</country>
    <country>France</country>
    <country>Germany</country>
    <country>Netherlands</country>
    <country>New Zealand</country>
    <country>Poland</country>
    <country>Singapore</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.amgentrials.com</url>
    <description>AmgenTrials clinical trials website</description>
  </link>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>August 17, 2017</study_first_submitted>
  <study_first_submitted_qc>September 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 8, 2017</study_first_posted>
  <results_first_submitted>March 30, 2022</results_first_submitted>
  <results_first_submitted_qc>March 30, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">August 8, 2022</results_first_posted>
  <last_update_submitted>March 30, 2022</last_update_submitted>
  <last_update_submitted_qc>March 30, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Heart Failure</keyword>
  <keyword>Cardiovascular Diseases</keyword>
  <keyword>Heart Diseases</keyword>
  <keyword>Ejection fraction</keyword>
  <keyword>Heart Failure with reduced ejection fraction</keyword>
  <keyword>Heart Failure with preserved ejection fraction</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.</ipd_time_frame>
    <ipd_access_criteria>Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.</ipd_access_criteria>
    <ipd_url>https://www.amgen.com/datasharing</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>July 27, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/28/NCT03276728/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 17, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/28/NCT03276728/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were enrolled at 13 study centers in 7 countries (Canada, France, New Zealand, Netherland, Poland, Singapore, United States).&#xD;
The study included Parts A, B (healthy volunteers) and C (participants with either heart failure with reduced ejection fraction [HFrEF] or heart failure with preserved ejection fraction [HFpEF]). Each part of the study consisted of ascending dose cohorts.</recruitment_details>
      <pre_assignment_details>Within each dose cohort participants were randomized to AMG 986 or placebo in a 3:1 ratio. At the conclusion of each cohort, safety and tolerability of AMG 986 was reviewed before advancing to the next dose cohort.&#xD;
The Statistical Analysis Plan for this study specified that AMG 986 and Placebo-treated participants in Part A and Part B would be combined to form pooled AMG 986 and placebo groups, respectively for each Part.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Part A: Placebo Pooled</title>
          <description>Healthy participants were administered placebo either intravenously (IV) or by mouth (PO) to match the 5 IV cohorts and 6 PO cohorts of AMG 986.</description>
        </group>
        <group group_id="P2">
          <title>Part A: AMG 986 Pooled</title>
          <description>Healthy participants were administered a single dose of AMG 986 either IV or PO. The 5 IV cohorts started at a 0.5 mg loading dose over one hour up to the Cohort 5 IV dosage of a 60 mg loading dose over 1 hour and a 360 mg maintenance dose lasting 23 hours. The 6 PO cohorts started at a single 5 mg dose up to the Cohort 6 PO dose of 650 mg.</description>
        </group>
        <group group_id="P3">
          <title>Part B: Placebo Pooled</title>
          <description>Healthy participants were administered placebo either IV for 4 consecutive days or PO for 7 days to match the 2 IV cohorts and 6 PO cohorts of AMG 986.</description>
        </group>
        <group group_id="P4">
          <title>Part B: AMG 986 Pooled</title>
          <description>Healthy participants were administered AMG 986 either IV or PO. IV cohort 1 was administered a loading dose of 6 mg over one hour followed by maintenance doses of 36 mg lasting 23 hours on day 1 and 38 mg lasting 24 hours on days 2-4. IV cohort 2 was administered a loading dose of 60 mg lasting one hour followed by maintenance doses of 360 mg lasting 23 hours on day 1 and 376 mg lasting 24 hours on days 2-4. The 6 PO cohorts started at 5 mg for 7 days up to Cohort 6 PO dose of 650 mg for 7 days.</description>
        </group>
        <group group_id="P5">
          <title>Part C: HFrEF Placebo</title>
          <description>Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO placebo tablet daily from days 1-21.</description>
        </group>
        <group group_id="P6">
          <title>Part C: HFpEF Placebo</title>
          <description>Participants with heart failure with preserved ejection fraction (HFpEF) were administered a single PO placebo tablet daily from days 1-21.</description>
        </group>
        <group group_id="P7">
          <title>Part C: HFrEF AMG 986</title>
          <description>Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO AMG 986 tablet daily from days 1-21 in ascending doses of 10 mg for days 1-7, 30 mg for days 8-14 and 100 mg for days 15-21.</description>
        </group>
        <group group_id="P8">
          <title>Part C: HFpEF AMG 986</title>
          <description>Participants with heart failure with preserved ejection fraction (HFpEF) were administered a single PO AMG 986 tablet daily from days 1-21 in ascending doses of 10 mg for days 1-7, 30 mg for days 8-14 and 100 mg for days 15-21.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="66"/>
                <participants group_id="P3" count="16"/>
                <participants group_id="P4" count="50"/>
                <participants group_id="P5" count="7"/>
                <participants group_id="P6" count="1"/>
                <participants group_id="P7" count="17"/>
                <participants group_id="P8" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treated Participants</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="66"/>
                <participants group_id="P3" count="16"/>
                <participants group_id="P4" count="50"/>
                <participants group_id="P5" count="7"/>
                <participants group_id="P6" count="1"/>
                <participants group_id="P7" count="16"/>
                <participants group_id="P8" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="66"/>
                <participants group_id="P3" count="14"/>
                <participants group_id="P4" count="45"/>
                <participants group_id="P5" count="6"/>
                <participants group_id="P6" count="1"/>
                <participants group_id="P7" count="15"/>
                <participants group_id="P8" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="5"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="2"/>
                <participants group_id="P8" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="2"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="3"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Decision by sponsor</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="2"/>
                <participants group_id="P8" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Part A: Placebo Pooled</title>
          <description>Healthy participants were administered placebo either intravenously (IV) or by mouth (PO) to match the 5 IV cohorts and 6 PO cohorts of AMG 986.</description>
        </group>
        <group group_id="B2">
          <title>Part A: AMG 986 Pooled</title>
          <description>Healthy participants were administered a single dose of AMG 986 either IV or PO. The 5 IV cohorts started at a 0.5 mg loading dose over one hour up to the Cohort 5 IV dosage of a 60 mg loading dose over 1 hour and a 360 mg maintenance dose lasting 23 hours. The 6 PO cohorts started at a single 5 mg dose up to the Cohort 6 PO dose of 650 mg.</description>
        </group>
        <group group_id="B3">
          <title>Part B: Placebo Pooled</title>
          <description>Healthy participants were administered placebo either IV for 4 consecutive days or PO for 7 days to match the 2 IV cohorts and 6 PO cohorts of AMG 986.</description>
        </group>
        <group group_id="B4">
          <title>Part B: AMG 986 Pooled</title>
          <description>Healthy participants were administered AMG 986 either IV or PO. IV cohort 1 was administered a loading dose of 6 mg over one hour followed by maintenance doses of 36 mg lasting 23 hours on day 1 and 38 mg lasting 24 hours on days 2-4. IV cohort 2 was administered a loading dose of 60 mg lasting one hour followed by maintenance doses of 360 mg lasting 23 hours on day 1 and 376 mg lasting 24 hours on days 2-4. The 6 PO cohorts started at 5 mg for 7 days up to Cohort 6 PO dose of 650 mg for 7 days.</description>
        </group>
        <group group_id="B5">
          <title>Part C: HFrEF Placebo</title>
          <description>Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO placebo tablet daily from days 1-21.</description>
        </group>
        <group group_id="B6">
          <title>Part C: HFpEF Placebo</title>
          <description>Participants with heart failure with preserved ejection fraction (HFpEF) were administered a single PO placebo tablet daily from days 1-21.</description>
        </group>
        <group group_id="B7">
          <title>Part C: HFrEF AMG 986</title>
          <description>Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO AMG 986 tablet daily from days 1-21 in ascending doses of 10 mg for days 1-7, 30 mg for days 8-14 and 100 mg for days 15-21.</description>
        </group>
        <group group_id="B8">
          <title>Part C: HFpEF AMG 986</title>
          <description>Participants with heart failure with preserved ejection fraction (HFpEF) were administered a single PO AMG 986 tablet daily from days 1-21 in ascending doses of 10 mg for days 1-7, 30 mg for days 8-14 and 100 mg for days 15-21.</description>
        </group>
        <group group_id="B9">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="22"/>
            <count group_id="B2" value="66"/>
            <count group_id="B3" value="16"/>
            <count group_id="B4" value="50"/>
            <count group_id="B5" value="7"/>
            <count group_id="B6" value="1"/>
            <count group_id="B7" value="17"/>
            <count group_id="B8" value="3"/>
            <count group_id="B9" value="182"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="37.2" spread="9.4"/>
                    <measurement group_id="B2" value="39.5" spread="9.8"/>
                    <measurement group_id="B3" value="36.9" spread="10.0"/>
                    <measurement group_id="B4" value="37.4" spread="9.8"/>
                    <measurement group_id="B5" value="61.6" spread="10.1"/>
                    <measurement group_id="B6" value="73.0"/>
                    <measurement group_id="B7" value="64.3" spread="7.8"/>
                    <measurement group_id="B8" value="69.0" spread="1.0"/>
                    <measurement group_id="B9" value="42.3" spread="13.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>18-64 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="66"/>
                    <measurement group_id="B3" value="16"/>
                    <measurement group_id="B4" value="50"/>
                    <measurement group_id="B5" value="4"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="11"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="169"/>
                  </measurement_list>
                </category>
                <category>
                  <title>65-84 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="6"/>
                    <measurement group_id="B8" value="3"/>
                    <measurement group_id="B9" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>85 years and over</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="3"/>
                    <measurement group_id="B8" value="2"/>
                    <measurement group_id="B9" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="59"/>
                    <measurement group_id="B3" value="16"/>
                    <measurement group_id="B4" value="49"/>
                    <measurement group_id="B5" value="4"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="14"/>
                    <measurement group_id="B8" value="1"/>
                    <measurement group_id="B9" value="165"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="35"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="44"/>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="45"/>
                    <measurement group_id="B5" value="6"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="17"/>
                    <measurement group_id="B8" value="2"/>
                    <measurement group_id="B9" value="146"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="1"/>
                    <measurement group_id="B9" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="11"/>
                    <measurement group_id="B5" value="2"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="2"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="30"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="17"/>
                    <measurement group_id="B5" value="2"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="7"/>
                    <measurement group_id="B8" value="2"/>
                    <measurement group_id="B9" value="54"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="35"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="18"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="8"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="81"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="1"/>
                    <measurement group_id="B9" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Multiple</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Participants With Treatment Emergent Adverse Events (TEAE)</title>
        <description>An adverse event is defined as any untoward medical occurrence in a clinical trial subject. The event does not necessarily have a causal relationship with study treatment. Events categorized as TEAEs started on or after first dose of study drug and include up to 30 days after the last dose.&#xD;
A serious AE is an AE that met one or more of the following criteria:&#xD;
Death&#xD;
Life-threatening&#xD;
Required inpatient hospitalization or prolongation of an existing hospitalization&#xD;
Resulted in persistent or significant disability/incapacity&#xD;
A congenital anomaly/birth defect&#xD;
Important medical events that required medical or surgical intervention to prevent one of the outcomes above.</description>
        <time_frame>Part A: Day 1 up to Day 31 Part B: Day 1 up to Day 37 Part C: Day 1 up to Day 51</time_frame>
        <population>All participants who received at least 1 dose of study drug</population>
        <group_list>
          <group group_id="O1">
            <title>Part A: Placebo Pooled</title>
            <description>Healthy participants were administered placebo either intravenously (IV) or by mouth (PO) to match the 5 IV cohorts and 6 PO cohorts of AMG 986.</description>
          </group>
          <group group_id="O2">
            <title>Part A: AMG 986 Pooled</title>
            <description>Healthy participants were administered a single dose of AMG 986 either IV or PO. The 5 IV cohorts started at a 0.5 mg loading dose over one hour up to the Cohort 5 IV dosage of a 60 mg loading dose over 1 hour and a 360 mg maintenance dose lasting 23 hours. The 6 PO cohorts started at a single 5 mg dose up to the Cohort 6 PO dose of 650 mg.</description>
          </group>
          <group group_id="O3">
            <title>Part B: Placebo Pooled</title>
            <description>Healthy participants were administered placebo either IV for 4 consecutive days or PO for 7 days to match the 2 IV cohorts and 6 PO cohorts of AMG 986.</description>
          </group>
          <group group_id="O4">
            <title>Part B: AMG 986 Pooled</title>
            <description>Healthy participants were administered AMG 986 either IV or PO. IV cohort 1 was administered a loading dose of 6 mg over one hour followed by maintenance doses of 36 mg lasting 23 hours on day 1 and 38 mg lasting 24 hours on days 2-4. IV cohort 2 was administered a loading dose of 60 mg lasting one hour followed by maintenance doses of 360 mg lasting 23 hours on day 1 and 376 mg lasting 24 hours on days 2-4. The 6 PO cohorts started at 5 mg for 7 days up to Cohort 6 PO dose of 650 mg for 7 days.</description>
          </group>
          <group group_id="O5">
            <title>Part C: HFrEF Placebo</title>
            <description>Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO placebo tablet daily from days 1-21.</description>
          </group>
          <group group_id="O6">
            <title>Part C: HFpEF Placebo</title>
            <description>Participants with heart failure with preserved ejection fraction (HFpEF) were administered a single PO placebo tablet daily from days 1-21.</description>
          </group>
          <group group_id="O7">
            <title>Part C: HFrEF AMG 986</title>
            <description>Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO AMG 986 tablet daily from days 1-21 in ascending doses of 10 mg for days 1-7, 30 mg for days 8-14 and 100 mg for days 15-21.</description>
          </group>
          <group group_id="O8">
            <title>Part C: HFpEF AMG 986</title>
            <description>Participants with heart failure with preserved ejection fraction (HFpEF) were administered a single PO AMG 986 tablet daily from days 1-21 in ascending doses of 10 mg for days 1-7, 30 mg for days 8-14 and 100 mg for days 15-21.</description>
          </group>
        </group_list>
        <measure>
          <title>Participants With Treatment Emergent Adverse Events (TEAE)</title>
          <description>An adverse event is defined as any untoward medical occurrence in a clinical trial subject. The event does not necessarily have a causal relationship with study treatment. Events categorized as TEAEs started on or after first dose of study drug and include up to 30 days after the last dose.&#xD;
A serious AE is an AE that met one or more of the following criteria:&#xD;
Death&#xD;
Life-threatening&#xD;
Required inpatient hospitalization or prolongation of an existing hospitalization&#xD;
Resulted in persistent or significant disability/incapacity&#xD;
A congenital anomaly/birth defect&#xD;
Important medical events that required medical or surgical intervention to prevent one of the outcomes above.</description>
          <population>All participants who received at least 1 dose of study drug</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
                <count group_id="O2" value="66"/>
                <count group_id="O3" value="16"/>
                <count group_id="O4" value="50"/>
                <count group_id="O5" value="7"/>
                <count group_id="O6" value="1"/>
                <count group_id="O7" value="16"/>
                <count group_id="O8" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>All treatment-emergent adverse events (TEAEs)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="11"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="7"/>
                    <measurement group_id="O5" value="2"/>
                    <measurement group_id="O6" value="1"/>
                    <measurement group_id="O7" value="6"/>
                    <measurement group_id="O8" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious adverse events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                    <measurement group_id="O7" value="0"/>
                    <measurement group_id="O8" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAEs leading to discontinuation of study drug</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                    <measurement group_id="O7" value="1"/>
                    <measurement group_id="O8" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fatal adverse events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                    <measurement group_id="O7" value="0"/>
                    <measurement group_id="O8" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Left Ventricular Ejection Fraction by Visit for Part C Heart Failure With Reduced Ejection Fraction (HFrEF) Cohort</title>
        <description>Heart failure (HF) refers to a clinical condition in which the cardiac output is insufficient to meet the metabolic needs of body organs and is marked by cardiac systolic and/or diastolic dysfunction. Heart failure with predominantly systolic dysfunction, which is identifiable as decreased contraction, is more aptly described as heart failure with reduced ejection fraction (HFrEF). Ejection fraction is a measurement, expressed as a percentage, of how much blood the left ventricle pumps out with each contraction and is measured by echocardiogram.</description>
        <time_frame>Baseline (Day 1 predose), Day 8, Day 15, Day 21, Day 30</time_frame>
        <population>Participants who received study drug with available LVEF at each time point</population>
        <group_list>
          <group group_id="O1">
            <title>Part C: HFrEF Placebo</title>
            <description>Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO placebo tablet daily from Days 1-21.</description>
          </group>
          <group group_id="O2">
            <title>Part C: HFrEF AMG 986</title>
            <description>Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO AMG 986 tablet daily from Days 1-21 in ascending doses of 10 mg for Days 1-7, 30 mg for Days 8-14 and 100 mg for days 15-21.</description>
          </group>
        </group_list>
        <measure>
          <title>Left Ventricular Ejection Fraction by Visit for Part C Heart Failure With Reduced Ejection Fraction (HFrEF) Cohort</title>
          <description>Heart failure (HF) refers to a clinical condition in which the cardiac output is insufficient to meet the metabolic needs of body organs and is marked by cardiac systolic and/or diastolic dysfunction. Heart failure with predominantly systolic dysfunction, which is identifiable as decreased contraction, is more aptly described as heart failure with reduced ejection fraction (HFrEF). Ejection fraction is a measurement, expressed as a percentage, of how much blood the left ventricle pumps out with each contraction and is measured by echocardiogram.</description>
          <population>Participants who received study drug with available LVEF at each time point</population>
          <units>percent of total left ventricular blood</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.300" spread="8.420"/>
                    <measurement group_id="O2" value="28.380" spread="6.483"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="34.900" spread="12.441"/>
                    <measurement group_id="O2" value="32.553" spread="7.055"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="14"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.533" spread="9.194"/>
                    <measurement group_id="O2" value="31.614" spread="7.154"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="14"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.550" spread="8.896"/>
                    <measurement group_id="O2" value="31.436" spread="5.953"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 30</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.171" spread="8.140"/>
                    <measurement group_id="O2" value="31.987" spread="7.036"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Stroke Volume (Method of Disks, Volumetric Assessment) by Visit for Part C Heart Failure With Reduced Ejection Fraction (HFrEF) Cohort</title>
        <description>Stroke volume is the amount of blood pumped by the left ventricle of the heart in one contraction reported by volumetric method of disks (MoD) assessment.</description>
        <time_frame>Baseline (Day 1 predose), Day 8, Day 15, Day 21, Day 30</time_frame>
        <population>Participants who received study drug with available data at each time point</population>
        <group_list>
          <group group_id="O1">
            <title>Part C: HFrEF Placebo</title>
            <description>Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO placebo tablet daily from Days 1-21.</description>
          </group>
          <group group_id="O2">
            <title>Part C: HFrEF AMG 986</title>
            <description>Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO AMG 986 tablet daily from Days 1-21 in ascending doses of 10 mg for Days 1-7, 30 mg for Days 8-14 and 100 mg for days 15-21.</description>
          </group>
        </group_list>
        <measure>
          <title>Stroke Volume (Method of Disks, Volumetric Assessment) by Visit for Part C Heart Failure With Reduced Ejection Fraction (HFrEF) Cohort</title>
          <description>Stroke volume is the amount of blood pumped by the left ventricle of the heart in one contraction reported by volumetric method of disks (MoD) assessment.</description>
          <population>Participants who received study drug with available data at each time point</population>
          <units>mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="53.387" spread="16.995"/>
                    <measurement group_id="O2" value="40.461" spread="14.193"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="55.185" spread="19.158"/>
                    <measurement group_id="O2" value="46.130" spread="13.927"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="14"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52.673" spread="19.514"/>
                    <measurement group_id="O2" value="46.784" spread="14.348"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="14"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="54.113" spread="18.789"/>
                    <measurement group_id="O2" value="44.014" spread="12.051"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 30</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="53.621" spread="19.258"/>
                    <measurement group_id="O2" value="44.634" spread="13.491"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Stroke Volume (Left Ventricular Outflow Tract Using Doppler Assessment) by Visit for Part C Heart Failure With Reduced Ejection Fraction (HFrEF) Cohort</title>
        <description>Stroke volume is the amount of blood pumped by the left ventricle of the heart in one contraction as measured using left ventricular outflow tract (LVOT) Doppler assessment.</description>
        <time_frame>Baseline (Day 1 predose), Day 8, Day 15, Day 21, Day 30</time_frame>
        <population>Participants who received study drug with available data at each time point</population>
        <group_list>
          <group group_id="O1">
            <title>Part C: HFrEF Placebo</title>
            <description>Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO placebo tablet daily from Days 1-21.</description>
          </group>
          <group group_id="O2">
            <title>Part C: HFrEF AMG 986</title>
            <description>Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO AMG 986 tablet daily from Days 1-21 in ascending doses of 10 mg for Days 1-7, 30 mg for Days 8-14 and 100 mg for days 15-21.</description>
          </group>
        </group_list>
        <measure>
          <title>Stroke Volume (Left Ventricular Outflow Tract Using Doppler Assessment) by Visit for Part C Heart Failure With Reduced Ejection Fraction (HFrEF) Cohort</title>
          <description>Stroke volume is the amount of blood pumped by the left ventricle of the heart in one contraction as measured using left ventricular outflow tract (LVOT) Doppler assessment.</description>
          <population>Participants who received study drug with available data at each time point</population>
          <units>mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="14"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59.056" spread="18.120"/>
                    <measurement group_id="O2" value="54.739" spread="14.523"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="14"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52.657" spread="13.231"/>
                    <measurement group_id="O2" value="53.512" spread="14.943"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="53.985" spread="21.580"/>
                    <measurement group_id="O2" value="53.073" spread="14.747"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="55.805" spread="26.127"/>
                    <measurement group_id="O2" value="53.858" spread="14.339"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 30</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="14"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="55.113" spread="20.900"/>
                    <measurement group_id="O2" value="50.616" spread="14.212"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Part A: Day 1 up to Day 31 Part B: Day 1 up to Day 37 Part C: Day 1 up to Day 51</time_frame>
      <desc>All-cause mortality is reported for all participants randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>Part A: Placebo Pooled</title>
          <description>Healthy participants were administered placebo either intravenously (IV) or by mouth (PO) to match the 5 IV cohorts and 6 PO cohorts of AMG 986.</description>
        </group>
        <group group_id="E2">
          <title>Part A: AMG 986 Pooled</title>
          <description>Healthy participants were administered a single dose of AMG 986 either IV or PO. The 5 IV cohorts started at a 0.5 mg loading dose over one hour up to the Cohort 5 IV dosage of a 60 mg loading dose over 1 hour and a 360 mg maintenance dose lasting 23 hours. The 6 PO cohorts started at a single 5 mg dose up to the Cohort 6 PO dose of 650 mg.</description>
        </group>
        <group group_id="E3">
          <title>Part B: Placebo Pooled</title>
          <description>Healthy participants were administered placebo either IV for 4 consecutive days or PO for 7 days to match the 2 IV cohorts and 6 PO cohorts of AMG 986.</description>
        </group>
        <group group_id="E4">
          <title>Part B: AMG 986 Pooled</title>
          <description>Healthy participants were administered AMG 986 either IV or PO. IV cohort 1 was administered a loading dose of 6 mg over one hour followed by maintenance doses of 36 mg lasting 23 hours on day 1 and 38 mg lasting 24 hours on days 2-4. IV cohort 2 was administered a loading dose of 60 mg lasting one hour followed by maintenance doses of 360 mg lasting 23 hours on day 1 and 376 mg lasting 24 hours on days 2-4. The 6 PO cohorts started at 5 mg for 7 days up to Cohort 6 PO dose of 650 mg for 7 days.</description>
        </group>
        <group group_id="E5">
          <title>Part C: HFrEF Placebo</title>
          <description>Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO placebo tablet daily from days 1-21.</description>
        </group>
        <group group_id="E6">
          <title>Part C: HFpEF Placebo</title>
          <description>Participants with heart failure with preserved ejection fraction (HFpEF) were administered a single PO placebo tablet daily from days 1-21.</description>
        </group>
        <group group_id="E7">
          <title>Part C: HFrEF AMG 986</title>
          <description>Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO AMG 986 tablet daily from days 1-21 in ascending doses of 10 mg for days 1-7, 30 mg for days 8-14 and 100 mg for days 15-21.</description>
        </group>
        <group group_id="E8">
          <title>Part C: HFpEF AMG 986</title>
          <description>Participants with heart failure with preserved ejection fraction (HFpEF) were administered a single PO AMG 986 tablet daily from days 1-21 in ascending doses of 10 mg for days 1-7, 30 mg for days 8-14 and 100 mg for days 15-21.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 22.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pleuritic pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2</frequency_threshold>
        <default_vocab>MedDRA 22.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="6" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="3" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Swelling of eyelid</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Oral mucosal eruption</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Blood creatine phosphokinase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Social avoidant behaviour</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Skin irritation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>This study was terminated early because the clinical development program was terminated. Therefore, no formal PK or pharmacodynamic analyses were conducted.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>IHQ Medical Info-Clinical Trials</name_or_title>
      <organization>Amgen (EUROPE) GmbH</organization>
      <phone>866-572-6436</phone>
      <email>MedInfoInternational@amgen.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03276728
org study id: 20150183
secondary id: 2017-002940-34
nct id: NCT03276728
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
To evaluate the safety and tolerability of ascending single (Part A) and ascending multiple
      (Part B) doses of AMG 986 in healthy adults and of ascending multiple oral doses of AMG 986
      in heart failure patients (Part C).
This study is a randomized, placebo-controlled, double-blind, single day ascending dose
      (SDAD) study (Part A), a multiple daily ascending dose (MDAD) study (Part B), in healthy
      adults, and a MDAD study (Part C) in heart failure patients. In Parts A and B of the study,
      healthy volunteers will receive AMG 986 by continuous IV infusion or by oral administration
      in a fasted state. IV Infusions will be divided into an initial loading dose (LD) for the
      first hour followed immediately by a maintenance dose (MD).

      In Part C of the study, patients with heart failure and either reduced (HFrEF) or preserved
      (HFpEF) ejection fraction will receive MDAD of AMG 986 or matching placebo once daily by oral
      administration for 21 days.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Double-blind, placebo-controlled
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: Double-blinded
measure: Participants With Treatment Emergent Adverse Events (TEAE)
time frame: Part A: Day 1 up to Day 31 Part B: Day 1 up to Day 37 Part C: Day 1 up to Day 51
description: An adverse event is defined as any untoward medical occurrence in a clinical trial subject. The event does not necessarily have a causal relationship with study treatment. Events categorized as TEAEs started on or after first dose of study drug and include up to 30 days after the last dose.
A serious AE is an AE that met one or more of the following criteria:
Death
Life-threatening
Required inpatient hospitalization or prolongation of an existing hospitalization
Resulted in persistent or significant disability/incapacity
A congenital anomaly/birth defect
Important medical events that required medical or surgical intervention to prevent one of the outcomes above.
measure: Left Ventricular Ejection Fraction by Visit for Part C Heart Failure With Reduced Ejection Fraction (HFrEF) Cohort
time frame: Baseline (Day 1 predose), Day 8, Day 15, Day 21, Day 30
description: Heart failure (HF) refers to a clinical condition in which the cardiac output is insufficient to meet the metabolic needs of body organs and is marked by cardiac systolic and/or diastolic dysfunction. Heart failure with predominantly systolic dysfunction, which is identifiable as decreased contraction, is more aptly described as heart failure with reduced ejection fraction (HFrEF). Ejection fraction is a measurement, expressed as a percentage, of how much blood the left ventricle pumps out with each contraction and is measured by echocardiogram.
measure: Stroke Volume (Method of Disks, Volumetric Assessment) by Visit for Part C Heart Failure With Reduced Ejection Fraction (HFrEF) Cohort
time frame: Baseline (Day 1 predose), Day 8, Day 15, Day 21, Day 30
description: Stroke volume is the amount of blood pumped by the left ventricle of the heart in one contraction reported by volumetric method of disks (MoD) assessment.
measure: Stroke Volume (Left Ventricular Outflow Tract Using Doppler Assessment) by Visit for Part C Heart Failure With Reduced Ejection Fraction (HFrEF) Cohort
time frame: Baseline (Day 1 predose), Day 8, Day 15, Day 21, Day 30
description: Stroke volume is the amount of blood pumped by the left ventricle of the heart in one contraction as measured using left ventricular outflow tract (LVOT) Doppler assessment.
arm group label: Part A: Placebo
arm group type: Placebo Comparator
description: Healthy participants were administered placebo either intravenously (IV) or by mouth (PO) to match the 5 IV cohorts and 6 PO cohorts of AMG 986.
arm group label: Part A: AMG 986
arm group type: Experimental
description: Healthy participants were administered a single dose of AMG 986 either IV or PO. The 5 IV cohorts started at a 0.5 mg loading dose over one hour up to to the Cohort 5 IV dosage consisting of a 60 mg loading dose over 1 hour and a 360 mg maintenance dose lasting 23 hours. The 6 PO cohorts started at a single 5 mg dose up to the Cohort 6 PO dose of 650 mg.
arm group label: Part B: Placebo
arm group type: Placebo Comparator
description: Healthy participants were administered placebo either IV for 4 consecutive days or PO for 7 days to match the 2 IV cohorts and 6 PO cohorts of AMG 986.
arm group label: Part B: AMG 986
arm group type: Experimental
description: Healthy participants were administered AMG 986 either IV or PO. IV cohort 1 was administered a loading dose of 6 mg over one hour followed by maintenance doses of 36 mg lasting 23 hours on Day 1 and 38 mg lasting 24 hours on Days 2-4. IV cohort 2 was administered a loading dose of 60 mg over one hour followed by maintenance doses of 360 mg lasting 23 hours on Day 1 and 376 mg lasting 24 hours on Days 2-4. The 6 PO cohorts started at 5 mg for 7 days up to Cohort 6 PO dose of 650 mg for 7 days.
arm group label: Part C: HFrEF Placebo
arm group type: Placebo Comparator
description: Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO placebo tablet daily from Days 1-21.
arm group label: Part C: HFpEF Placebo
arm group type: Placebo Comparator
description: Participants with heart failure with preserved ejection fraction (HFpEF) were administered a single PO placebo tablet daily from Days 1-21.
arm group label: Part C: HFrEF AMG 986
arm group type: Experimental
description: Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO AMG 986 tablet daily from Days 1-21 in ascending doses of 10 mg for Days 1-7, 30 mg for Days 8-14 and 100 mg for days 15-21.
arm group label: Part C: HFpEF AMG 986
arm group type: Experimental
description: Participants with heart failure with preserved ejection fraction (HFpEF) were administered a single PO AMG 986 tablet daily from Days 1-21 in ascending doses of 10 mg for Days 1-7, 30 mg for Days 8-14 and 100 mg for days 15-21.
intervention type: Drug
intervention name: AMG 986 IV
description: AMG 986 solution for infusion
arm group label: Part A: AMG 986
arm group label: Part B: AMG 986
intervention type: Drug
intervention name: AMG 986 PO
description: AMG 986 tablets for oral (PO) administration
arm group label: Part A: AMG 986
arm group label: Part B: AMG 986
arm group label: Part C: HFpEF AMG 986
arm group label: Part C: HFrEF AMG 986
intervention type: Drug
intervention name: Placebo PO
description: Matching placebo tablets for oral administration
arm group label: Part A: Placebo
arm group label: Part B: Placebo
arm group label: Part C: HFpEF Placebo
arm group label: Part C: HFrEF Placebo
intervention type: Drug
intervention name: Placebo IV
description: Matching placebo solution for infusion
arm group label: Part A: Placebo
arm group label: Part B: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: Accepts Healthy Volunteers
last name: MD
role: Study Director
affiliation: Amgen
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country: Australia
country: Canada
country: France
country: Germany
country: Netherlands
country: New Zealand
country: Poland
country: Singapore
country: United States
url: http://www.amgentrials.com
description: AmgenTrials clinical trials website
responsible party type: Sponsor
mesh term: Heart Failure
sharing ipd: Yes
ipd description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
ipd access criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
ipd url: https://www.amgen.com/datasharing
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: This study was terminated early because the clinical development program was terminated. Therefore, no formal PK or pharmacodynamic analyses were conducted.
point of contact: 