<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/NCT03759392</url>
  </required_header>
  <id_info>
    <org_study_id>CY 1031</org_study_id>
    <secondary_id>2018-001233-40</secondary_id>
    <nct_id>NCT03759392</nct_id>
  </id_info>
  <brief_title>Study to Assess the Effect of Omecamtiv Mecarbil on Exercise Capacity in Subjects With Heart Failure</brief_title>
  <acronym>METEORIC-HF</acronym>
  <official_title>A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Assess the Effect of Omecamtiv Mecarbil on Exercise Capacity in Subjects With Heart Failure With Reduced Ejection Fraction and Decreased Exercise Tolerance</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cytokinetics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cytokinetics</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The purpose of this study is to evaluate the effect of treatment with omecamtiv mecarbil&#xD;
      compared with placebo on exercise capacity as determined by cardiopulmonary exercise testing&#xD;
      following 20 weeks of treatment with omecamtiv mecarbil or placebo&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Oversight Authorities:&#xD;
&#xD;
      United States: Food and Drug Administration Canada: Health Canada France: National Agency for&#xD;
      the Safety of Medicine and Health Products Germany: Federal Institute for Drugs and Medical&#xD;
      Devices Hungary: National Institute of Pharmacy and Nutrition Italy: Italian Medicines Agency&#xD;
      Netherlands: Medicines Evaluation Board Poland: Chief Pharmaceutical Inspectorate Sweden:&#xD;
      Medical Products Agency&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 9, 2019</start_date>
  <completion_date type="Actual">January 6, 2022</completion_date>
  <primary_completion_date type="Actual">November 8, 2021</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Peak Oxygen Uptake on Cardiopulmonary Exercise Testing From Baseline to Week 20</measure>
    <time_frame>Baseline and Week 20</time_frame>
    <description>The effect of treatment on exercise capacity, as assessed by peak oxygen uptake, was assessed during cardiopulmonary exercise testing (CPET) with gas-exchange analysis. Cycle ergometry was the preferred modality for exercise testing; treadmill exercise testing was an acceptable alternative. Participants were to use the same testing modality for all exercise tests during the study. Whenever possible, CPET was administered by the same study personnel using the same equipment throughout the study.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Total Workload During Cardiopulmonary Exercise Testing From Baseline to Week 20</measure>
    <time_frame>Baseline and Week 20</time_frame>
    <description>Total workload was measured during CPET (cycle ergometry [preferred] or treadmill exercise testing) and represents the maximum load to which a participant was subjected during CPET in order to produce work.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Ventilatory Efficiency During Cardiopulmonary Exercise Testing From Baseline to Week 20</measure>
    <time_frame>Baseline and Week 20</time_frame>
    <description>Ventilatory efficiency (ventilation [VE]/volume of exhaled carbon dioxide [VCO2]) was measured through CPET with gas exchange analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the Average Daily Activity Units Measured Over a 2-week Period From Baseline (Week -2 to Day 1) to Weeks 18-20</measure>
    <time_frame>Baseline (Week -2 to Day 1) to Weeks 18-20</time_frame>
    <description>The effect of treatment on daily activity, as assessed by average daily activity units, was evaluated by actigraphy. Actigraphy was collected during 4 sessions throughout the study for 2 week intervals.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">276</enrollment>
  <condition>Heart Failure With Reduced Ejection Fraction</condition>
  <arm_group>
    <arm_group_label>Omecamtiv Mecarbil</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Omecamtiv mecarbil was administered as an oral modified-release tablet twice daily for up to 20 weeks. Participants randomized to this arm started at an omecamtiv mecarbil dose of 25 mg twice daily. The dose could be increased based on plasma concentrations at Weeks 2 and 6.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants randomized this arm received placebo tablets (matching the appearance of the omecamtiv mecarbil tablets) twice daily for up to 20 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Omecamtiv Mecarbil</intervention_name>
    <description>Oral omecamtiv mecarbil twice daily for up to 20 weeks with dose level determined by periodic blood testing</description>
    <arm_group_label>Omecamtiv Mecarbil</arm_group_label>
    <other_name>CK-1827452</other_name>
    <other_name>AMG-423</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Oral placebo twice daily for up to 20 weeks</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          -  Male or female, greater than or equal to 18 to lesser than or equal to 85 years of age&#xD;
&#xD;
          -  History of chronic HF, defined as requiring continuous treatment with medications for&#xD;
             HF for a minimum of 3 months before screening&#xD;
&#xD;
          -  New York Heart Association (NYHA) class II or III at screening&#xD;
&#xD;
          -  Left ventricular ejection fraction less than or equal to 35%&#xD;
&#xD;
          -  On maximally tolerated HF standard of care (SoC) therapies consistent with regional&#xD;
             clinical practice guidelines, if not contraindicated and according to investigator&#xD;
             judgment of the subject's clinical status. Beta blocker dose must be stable for 30&#xD;
             days prior to randomization.&#xD;
&#xD;
          -  N-terminal (NT)-proBNP level greater than or equal to 200 pg/mL&#xD;
&#xD;
          -  Peak VO2 less than or equal to 75% of the predicted normal value with respiratory&#xD;
             exchange ratio (RER) greater than or equal to 1.05 on a screening CPET, confirmed by a&#xD;
             CPET core laboratory&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  Severe uncorrected valvular heart disease&#xD;
&#xD;
          -  Paroxysmal atrial fibrillation or flutter documented within the previous 6 months,&#xD;
             direct-current (DC) cardioversion or ablation procedure for atrial fibrillation within&#xD;
             6 months, or plan to attempt to restore sinus rhythm within 6 months of randomization.&#xD;
             Subjects with persistent atrial fibrillation and no sinus rhythm documented in the&#xD;
             prior 6 months are permitted.&#xD;
&#xD;
          -  Symptomatic bradycardia, second-degree Mobitz type II, or third-degree heart block&#xD;
             without a pacemaker.&#xD;
&#xD;
          -  History of gastrointestinal bleeding requiring hospitalization, urgent procedure or&#xD;
             transfusion in the prior year, or received intravenous (IV) iron, blood transfusion,&#xD;
             or an erythropoiesis-stimulating agent (ESA) within 3 months prior to screening, or&#xD;
             planned blood transfusion or ESA use during the study screening or treatment period.&#xD;
             Chronic, stable use of oral iron is permitted.&#xD;
&#xD;
          -  Ongoing or planned enrollment in cardiac rehabilitation.&#xD;
&#xD;
          -  Requires assistance to walk or use of mobility assistive devices such as motorized&#xD;
             devices, wheelchairs, or walkers. The use of canes for stability while ambulating is&#xD;
             acceptable if the subject is deemed capable of performing CPET.&#xD;
&#xD;
          -  Major medical event or procedure within 3 months prior to randomization, including:&#xD;
             hospitalization, surgery, renal replacement therapy or cardiac procedure. This&#xD;
             includes episodes of decompensated HF that require IV HF treatment.&#xD;
&#xD;
          -  At screening: Resting systolic BP greater than 140 mmHg or less than 85 mmHg, or&#xD;
             diastolic BP greater than 90 mmHg (mean of triplicate readings); Resting heart rate&#xD;
             greater than 90 beats per minute, or less than 50 beats per minute (mean of triplicate&#xD;
             readings); Estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73m2 (by&#xD;
             the modified Modification of Diet in Renal Disease equation); Hepatic impairment&#xD;
             defined by a total bilirubin (TBL) greater than or equal to 2 times the upper limit of&#xD;
             normal (ULN), or alanine aminotransferase (ALT) or aspartate aminotransferase (AST)&#xD;
             greater than or equal to 3 times ULN. Patients with documented Gilbert syndrome and&#xD;
             TBL greater than or equal to 2 times ULN due to unconjugated hyperbilirubinemia,&#xD;
             without other hepatic impairment, are permitted.&#xD;
&#xD;
          -  Room air oxygen saturation under 90% at screening&#xD;
&#xD;
          -  Hemoglobin less than 10.0 g/dL at screening&#xD;
&#xD;
          -  Significant adverse finding (e.g., exercise-induced early ischemic changes, abnormal&#xD;
             decrease in BP [systolic BP falls by more than 10 mmHg], unexpected arrhythmia or&#xD;
             other serious finding) during CPET at screening that precludes safe participation in&#xD;
             the study, per investigator&#xD;
&#xD;
          -  Chronotropic incompetence (including inadequate pacemaker rate response) during CPET&#xD;
             at screening, defined as a maximum heart rate &lt;60% of the maximum predicted heart rate&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Cytokinetics, MD</last_name>
    <role>Study Director</role>
    <affiliation>Cytokinetics</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Alaska Heart and Vascular Institute</name>
      <address>
        <city>Anchorage</city>
        <state>Alaska</state>
        <zip>99508</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arkansas Cardiology Clinic</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Harbor-UCLA Medical Center</name>
      <address>
        <city>Torrance</city>
        <state>California</state>
        <zip>90509</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>South Denver Cardiology Associates, PC</name>
      <address>
        <city>Littleton</city>
        <state>Colorado</state>
        <zip>80120</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hartford Hospital-University of Connecticut School of Medicine</name>
      <address>
        <city>Hartford</city>
        <state>Connecticut</state>
        <zip>06102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Holy Cross Hospital - Fort Lauderdale</name>
      <address>
        <city>Fort Lauderdale</city>
        <state>Florida</state>
        <zip>33308-4603</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Broward Research Center - Pembroke Pines</name>
      <address>
        <city>Pembroke Pines</city>
        <state>Florida</state>
        <zip>33024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Community Hospital South, Inc.</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46227</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Vincent Medical Group Inc.</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46260</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Maryland</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital (MGH) - Cardiac Unit Associates</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114-2621</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Heart &amp; Vascular Institute</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McLaren Health Care Corporation</name>
      <address>
        <city>Petoskey</city>
        <state>Michigan</state>
        <zip>49770</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Michigan Heart</name>
      <address>
        <city>Ypsilanti</city>
        <state>Michigan</state>
        <zip>48197</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Luke's Health System</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Glacier View Research Institute, Cardiology</name>
      <address>
        <city>Kalispell</city>
        <state>Montana</state>
        <zip>59901</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Nebraska Medical Center</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68198</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cardiovascular Associates Of The Delaware Valley (Cadv), P.A. - Elmer Physicians Care Center - Elmer</name>
      <address>
        <city>Elmer</city>
        <state>New Jersey</state>
        <zip>08318</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Newark Beth Israel Medical Center</name>
      <address>
        <city>Newark</city>
        <state>New Jersey</state>
        <zip>07112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NYU Langone Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queens Heart Institute</name>
      <address>
        <city>Rosedale</city>
        <state>New York</state>
        <zip>11422</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wake Med Health and Hospital</name>
      <address>
        <city>Raleigh</city>
        <state>North Carolina</state>
        <zip>27610</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wake Forest University School of Medicine</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ohio State University</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. John Clinical Research Institute</name>
      <address>
        <city>Tulsa</city>
        <state>Oklahoma</state>
        <zip>74104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Capital Area Research, LLC</name>
      <address>
        <city>Camp Hill</city>
        <state>Pennsylvania</state>
        <zip>17011</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Penn State Hershey Children's Hospital</name>
      <address>
        <city>Hershey</city>
        <state>Pennsylvania</state>
        <zip>17033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lancaster Heart And Stroke Foundation</name>
      <address>
        <city>Lancaster</city>
        <state>Pennsylvania</state>
        <zip>17603</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greenville Health System</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas - Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor Scott and White Heart and Vascular Hospital</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inova Heart and Vascular Institute</name>
      <address>
        <city>Falls Church</city>
        <state>Virginia</state>
        <zip>22042</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Foothills Medical Centre</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N 4Z6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>London Health Sciences Centre - University Hospital</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A 5A5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ecogene-21</name>
      <address>
        <city>Chicoutimi</city>
        <state>Quebec</state>
        <zip>G7H 7K9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universite de Montreal Institut de Cardiologie de Montreal ICM Montreal Heart Institute MHI</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H1Y 3N1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mcgill University Health Centre (MUHC)-The Montreal General Hospital (MGH)</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3P1E1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier De La Cote Basque</name>
      <address>
        <city>Bayonne cedex</city>
        <zip>64109</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Groupe Hospitalier Mutualiste de Grenoble</name>
      <address>
        <city>Grenoble</city>
        <zip>38028</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Universitaire de Grenoble-Hopital Albert Michallon</name>
      <address>
        <city>La Tronche</city>
        <zip>38700</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universite De Nantes - L'Institut Du Thorax</name>
      <address>
        <city>Nantes CEDEX 1</city>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Assistance Publique - Hopitaux de Paris (AP-HP) - Hopital Lariboisiere</name>
      <address>
        <city>Paris</city>
        <zip>75010</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chu de Rouen Hopital Charles Nicolle</name>
      <address>
        <city>Rouen Cedex</city>
        <zip>76031</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Universitaire (CHU) de Toulouse - Hopital Rangueil</name>
      <address>
        <city>Toulouse Cedex 9</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinik Heidelberg</name>
      <address>
        <city>Heidelberg</city>
        <state>Baden-wurttemberg</state>
        <zip>69120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitatsklinikum Magdeburg</name>
      <address>
        <city>Magdeburg</city>
        <state>Saxony-Anhalt</state>
        <zip>39120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Jena</name>
      <address>
        <city>Jena</city>
        <state>Thueringen</state>
        <zip>07747</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kerckhoff-Klinik- Bad Nauheim</name>
      <address>
        <city>Bad Nauheim</city>
        <zip>61231</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Praxisklinik Dresden</name>
      <address>
        <city>Dresden</city>
        <zip>01099</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Des Saarlandes Und Medizinische Fakultaet Der Universitaet Des Saarlandes</name>
      <address>
        <city>Homburg</city>
        <zip>66421</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Balatonfuredi Allami Szivkorhaz</name>
      <address>
        <city>Balatonfured</city>
        <zip>8230</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Semmelweis University Heart and Vascular Center</name>
      <address>
        <city>Budapest</city>
        <zip>1122</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pecsi Tudomanyegyetem (PTE) Altalanos Orvostudomanyi Kar (AOK) (University of Pecs Medical School)</name>
      <address>
        <city>Pecs</city>
        <zip>7624</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedali Riuniti Foggia</name>
      <address>
        <city>Foggia</city>
        <state>Apulia</state>
        <zip>71100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Cardiologico Monzino IRCCS</name>
      <address>
        <city>Milano</city>
        <state>Lombardia</state>
        <zip>20138</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera S.Orsola Malpighi</name>
      <address>
        <city>Bologna</city>
        <state>Province Of Bologna</state>
        <zip>40138</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Spedali Civili di Brescia-Universita degli Studi Di Brescia</name>
      <address>
        <city>Brescia</city>
        <state>Province Of Brescia</state>
        <zip>25123</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Insituto Di Ricovero E Cura A Carattere Scientifico San Raffaele Pisana</name>
      <address>
        <city>Roma</city>
        <state>Rome</state>
        <zip>00163</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Divisione di Cardiologia con Utic ed Emodinamica</name>
      <address>
        <city>Napoli</city>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Monaldi</name>
      <address>
        <city>Napoli</city>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Erasmus MC - Universitair Medisch Centrum Rotterdam</name>
      <address>
        <city>Rotterdam</city>
        <state>South Holland</state>
        <zip>3000 CA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jeroen Bosch Ziekenhuis</name>
      <address>
        <city>'S-Hertogenbosch</city>
        <zip>5223 GZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Onze Lieve Vrouwe Gasthuis (OLVG) Locatie West</name>
      <address>
        <city>Amsterdam</city>
        <zip>1061 AE</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Medical Center Groningen</name>
      <address>
        <city>Groningen</city>
        <zip>9713 GZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Leids Universitair Medisch Centrum (LUMC)</name>
      <address>
        <city>Leiden</city>
        <zip>2300RC</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Radboud Universiteit - Radboud Universitair Medisch Centrum (Radboudumc)</name>
      <address>
        <city>Nijmegen</city>
        <zip>6500 HB</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitair Medisch Centrum Utrecht - Wilhelmina Kinderziekenhuis</name>
      <address>
        <city>Utrecht</city>
        <zip>3584 CX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maxima Medisch Centrum Veldhoven</name>
      <address>
        <city>Veldhoven</city>
        <zip>5504 DB</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum Medyczne Medyk Sp z o.o. Sp. k.</name>
      <address>
        <city>Rzeszow</city>
        <state>Podkarpackie</state>
        <zip>35-055</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniwersytecki Szpital Kliniczny w Bialymstoku</name>
      <address>
        <city>Bialystok</city>
        <zip>15-276</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniwersyteckie Centrum Kliniczne Kliniczne Centrum Kardiologii</name>
      <address>
        <city>Gdansk</city>
        <zip>80-952</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oddzial Kliniczny Choroby Wiencowej i Niewydolnosci Serca z Pododdzialem Intensywnego Nadzoru Kardiologicznego</name>
      <address>
        <city>Krakow</city>
        <zip>31- 202</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika, Oddzial Kardiologiczny</name>
      <address>
        <city>Lodz</city>
        <zip>93-513</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instytut Kardiologii Heart Failure Clinic</name>
      <address>
        <city>Warsaw</city>
        <zip>04-628</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum Chorob Serca, Uniwersytecki Szpital Kllniczny im. Jana Mikulicza Radeckiego we Wrociawiu</name>
      <address>
        <city>Wroclaw</city>
        <zip>50556</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sahlgrenska Universitetssjukhuset</name>
      <address>
        <city>Göteborg</city>
        <zip>413 45</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Enhet Klinisk forskning, hjartmedicin, Skanes Universitet Sjukhus</name>
      <address>
        <city>Lund</city>
        <zip>22242</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>France</country>
    <country>Germany</country>
    <country>Hungary</country>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>Poland</country>
    <country>Sweden</country>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>November 15, 2018</study_first_submitted>
  <study_first_submitted_qc>November 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 30, 2018</study_first_posted>
  <results_first_submitted>January 6, 2023</results_first_submitted>
  <results_first_submitted_qc>February 11, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">March 7, 2023</results_first_posted>
  <last_update_submitted>February 11, 2023</last_update_submitted>
  <last_update_submitted_qc>February 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
  </condition_browse>
  <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>http://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>June 30, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/92/NCT03759392/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>January 5, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/92/NCT03759392/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants with heart failure with reduced ejection fraction (HFrEF) were enrolled at 63 sites in Canada, France, Germany, Hungary, Italy, Netherlands, Poland, Sweden, and the United States. The first participant enrolled on 09 April 2019, and the last participant completed follow-up on 06 January 2022.</recruitment_details>
      <pre_assignment_details>A total of 276 participants were randomized in a 2:1 ratio to treatment: 185 to omecamtiv mecarbil and 91 to placebo.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Omecamtiv Mecarbil</title>
          <description>Omecamtiv mecarbil was administered as an oral modified release tablet twice daily for up to 20 weeks. Participants randomized to this arm started at an omecamtiv mecarbil dose of 25 mg twice daily. The dose could be increased based on plasma concentrations at Weeks 2 and 6.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Participants randomized to this arm received placebo tablets (matching the appearance of the omecamtiv mecarbil tablets) twice daily for up to 20 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="185"/>
                <participants group_id="P2" count="91"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="164"/>
                <participants group_id="P2" count="85"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Consistently forgot to bring study drug kits to site visits (for compliance check)</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>No longer able to take medicines</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Stopped taking study drug</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Omecamtiv Mecarbil</title>
          <description>Omecamtiv mecarbil was administered as an oral modified-release tablet twice daily for up to 20 weeks. Participants randomized to this arm started at an omecamtiv mecarbil dose of 25 mg twice daily. The dose could be increased based on plasma concentrations at Weeks 2 and 6.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Participants randomized this arm received placebo tablets (matching the appearance of the omecamtiv mecarbil tablets) twice daily for up to 20 weeks.</description>
        </group>
        <group group_id="B3">
          <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="185"/>
            <count group_id="B2" value="91"/>
            <count group_id="B3" value="276"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="185"/>
                    <count group_id="B2" value="91"/>
                    <count group_id="B3" value="276"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="63.3" spread="9.64"/>
                    <measurement group_id="B2" value="64.4" spread="11.41"/>
                    <measurement group_id="B3" value="63.6" spread="10.25"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="185"/>
                    <count group_id="B2" value="91"/>
                    <count group_id="B3" value="276"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="42"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="158"/>
                    <measurement group_id="B2" value="76"/>
                    <measurement group_id="B3" value="234"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="185"/>
                    <count group_id="B2" value="91"/>
                    <count group_id="B3" value="276"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </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_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="163"/>
                    <measurement group_id="B2" value="82"/>
                    <measurement group_id="B3" value="245"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Time since HFrEF diagnosis</title>
          <population>The time since HFrEF diagnosis was missing for 1 participant in the omecamtiv mecarbil arm.</population>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="184"/>
                    <count group_id="B2" value="91"/>
                    <count group_id="B3" value="275"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7.6" spread="6.14"/>
                    <measurement group_id="B2" value="7.8" spread="6.88"/>
                    <measurement group_id="B3" value="7.7" spread="6.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Primary cause of heart failure: ischemic heart disease</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="185"/>
                    <count group_id="B2" value="91"/>
                    <count group_id="B3" value="276"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="117"/>
                    <measurement group_id="B2" value="48"/>
                    <measurement group_id="B3" value="165"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Peak Oxygen Uptake on Cardiopulmonary Exercise Testing From Baseline to Week 20</title>
        <description>The effect of treatment on exercise capacity, as assessed by peak oxygen uptake, was assessed during cardiopulmonary exercise testing (CPET) with gas-exchange analysis. Cycle ergometry was the preferred modality for exercise testing; treadmill exercise testing was an acceptable alternative. Participants were to use the same testing modality for all exercise tests during the study. Whenever possible, CPET was administered by the same study personnel using the same equipment throughout the study.</description>
        <time_frame>Baseline and Week 20</time_frame>
        <population>Full Analysis Set (all randomized participants who received at least 1 dose of randomized study drug)</population>
        <group_list>
          <group group_id="O1">
            <title>Omecamtiv Mecarbil</title>
            <description>Omecamtiv mecarbil was administered as an oral modified-release tablet twice daily for up to 20 weeks. Participants randomized to this arm started at an omecamtiv mecarbil dose of 25 mg twice daily. The dose could be increased based on plasma concentrations at Weeks 2 and 6.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants randomized this arm received placebo tablets (matching the appearance of the omecamtiv mecarbil tablets) twice daily for up to 20 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Peak Oxygen Uptake on Cardiopulmonary Exercise Testing From Baseline to Week 20</title>
          <description>The effect of treatment on exercise capacity, as assessed by peak oxygen uptake, was assessed during cardiopulmonary exercise testing (CPET) with gas-exchange analysis. Cycle ergometry was the preferred modality for exercise testing; treadmill exercise testing was an acceptable alternative. Participants were to use the same testing modality for all exercise tests during the study. Whenever possible, CPET was administered by the same study personnel using the same equipment throughout the study.</description>
          <population>Full Analysis Set (all randomized participants who received at least 1 dose of randomized study drug)</population>
          <units>mL/min/kg</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="162"/>
                <count group_id="O2" value="81"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.239" spread="0.1718"/>
                    <measurement group_id="O2" value="0.207" spread="0.2412"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.13</p_value>
            <method>ANCOVA</method>
            <method_desc>Using multiple imputation</method_desc>
            <param_type>Least squares mean difference</param_type>
            <param_value>-0.447</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.2931</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.024</ci_lower_limit>
            <ci_upper_limit>0.131</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Total Workload During Cardiopulmonary Exercise Testing From Baseline to Week 20</title>
        <description>Total workload was measured during CPET (cycle ergometry [preferred] or treadmill exercise testing) and represents the maximum load to which a participant was subjected during CPET in order to produce work.</description>
        <time_frame>Baseline and Week 20</time_frame>
        <population>Full Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>Omecamtiv Mecarbil</title>
            <description>Omecamtiv mecarbil was administered as an oral modified-release tablet twice daily for up to 20 weeks. Participants randomized to this arm started at an omecamtiv mecarbil dose of 25 mg twice daily. The dose could be increased based on plasma concentrations at Weeks 2 and 6.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants randomized this arm received placebo tablets (matching the appearance of the omecamtiv mecarbil tablets) twice daily for up to 20 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Total Workload During Cardiopulmonary Exercise Testing From Baseline to Week 20</title>
          <description>Total workload was measured during CPET (cycle ergometry [preferred] or treadmill exercise testing) and represents the maximum load to which a participant was subjected during CPET in order to produce work.</description>
          <population>Full Analysis Set</population>
          <units>Watt</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="162"/>
                <count group_id="O2" value="81"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.798" spread="1.3352"/>
                    <measurement group_id="O2" value="1.590" spread="1.9477"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.025</p_value>
            <method>ANCOVA</method>
            <method_desc>Using multiple imputation</method_desc>
            <param_type>Least squares mean difference</param_type>
            <param_value>-5.388</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>2.3937</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-10.108</ci_lower_limit>
            <ci_upper_limit>-0.0668</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Ventilatory Efficiency During Cardiopulmonary Exercise Testing From Baseline to Week 20</title>
        <description>Ventilatory efficiency (ventilation [VE]/volume of exhaled carbon dioxide [VCO2]) was measured through CPET with gas exchange analysis.</description>
        <time_frame>Baseline and Week 20</time_frame>
        <population>Full Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>Omecamtiv Mecarbil</title>
            <description>Omecamtiv mecarbil was administered as an oral modified-release tablet twice daily for up to 20 weeks. Participants randomized to this arm started at an omecamtiv mecarbil dose of 25 mg twice daily. The dose could be increased based on plasma concentrations at Weeks 2 and 6.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants randomized this arm received placebo tablets (matching the appearance of the omecamtiv mecarbil tablets) twice daily for up to 20 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Ventilatory Efficiency During Cardiopulmonary Exercise Testing From Baseline to Week 20</title>
          <description>Ventilatory efficiency (ventilation [VE]/volume of exhaled carbon dioxide [VCO2]) was measured through CPET with gas exchange analysis.</description>
          <population>Full Analysis Set</population>
          <units>slope</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="162"/>
                <count group_id="O2" value="81"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.277" spread="0.3616"/>
                    <measurement group_id="O2" value="-0.138" spread="0.5065"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.51</p_value>
            <method>ANCOVA</method>
            <method_desc>Using multiple imputation</method_desc>
            <param_type>Least squares mean difference</param_type>
            <param_value>0.414</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.6215</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.810</ci_lower_limit>
            <ci_upper_limit>1.639</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in the Average Daily Activity Units Measured Over a 2-week Period From Baseline (Week -2 to Day 1) to Weeks 18-20</title>
        <description>The effect of treatment on daily activity, as assessed by average daily activity units, was evaluated by actigraphy. Actigraphy was collected during 4 sessions throughout the study for 2 week intervals.</description>
        <time_frame>Baseline (Week -2 to Day 1) to Weeks 18-20</time_frame>
        <population>The analysis population included participants in the Full Analysis Set with available data at both assessment time frames (ie, baseline [Week -2 to Day 1] and Weeks 18-20).</population>
        <group_list>
          <group group_id="O1">
            <title>Omecamtiv Mecarbil</title>
            <description>Omecamtiv mecarbil was administered as an oral modified-release tablet twice daily for up to 20 weeks. Participants randomized to this arm started at an omecamtiv mecarbil dose of 25 mg twice daily. The dose could be increased based on plasma concentrations at Weeks 2 and 6.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants randomized this arm received placebo tablets (matching the appearance of the omecamtiv mecarbil tablets) twice daily for up to 20 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in the Average Daily Activity Units Measured Over a 2-week Period From Baseline (Week -2 to Day 1) to Weeks 18-20</title>
          <description>The effect of treatment on daily activity, as assessed by average daily activity units, was evaluated by actigraphy. Actigraphy was collected during 4 sessions throughout the study for 2 week intervals.</description>
          <population>The analysis population included participants in the Full Analysis Set with available data at both assessment time frames (ie, baseline [Week -2 to Day 1] and Weeks 18-20).</population>
          <units>10^5 activity units</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="147"/>
                <count group_id="O2" value="77"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.2" spread="0.30"/>
                    <measurement group_id="O2" value="-0.5" spread="0.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.54</p_value>
            <method>Repeated measures mixed model</method>
            <param_type>Least squares mean difference</param_type>
            <param_value>0.3</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.42</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.6</ci_lower_limit>
            <ci_upper_limit>1.1</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Omecamtiv Mecarbil</title>
          <description>Omecamtiv mecarbil was administered as an oral modified-release tablet twice daily for up to 20 weeks. Participants randomized to this arm started at an omecamtiv mecarbil dose of 25 mg twice daily. The dose could be increased based on plasma concentrations at Weeks 2 and 6.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Participants randomized this arm received placebo tablets (matching the appearance of the omecamtiv mecarbil tablets) twice daily for up to 20 weeks.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (23.0)</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="3" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="30" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Cardiac failure acute</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Cardiac failure congestive</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Ventricular tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Acute myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Cardio-respiratory arrest</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Ventricular fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Atrial flutter</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Supraventricular tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Small intestinal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Lower gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Pneumonia bacterial</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Anal abscess</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Abscess limb</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Multiple fractures</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Thermal burn</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Complications of transplanted heart</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetes mellitus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Gout</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Fluid retention</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Flank pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Colon cancer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebrovascular accident</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Ischaemic stroke</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Myasthenia gravis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Transient ischaemic attack</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Pulmonary oedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Heart transplant</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2</frequency_threshold>
        <default_vocab>MedDRA (23.0)</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="126" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="58" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Chest discomfort</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Gout</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="91"/>
              </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="6" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="91"/>
              </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="5" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Dyspnoea exertional</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="91"/>
              </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="4" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="91"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="91"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="185"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="91"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Cytokinetics MD</name_or_title>
      <organization>Cytokinetics, Inc.</organization>
      <phone>650-624-2929</phone>
      <email>medicalaffairs@cytokinetics.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/NCT03759392
org study id: CY 1031
secondary id: 2018-001233-40
nct id: NCT03759392
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to evaluate the effect of treatment with omecamtiv mecarbil
      compared with placebo on exercise capacity as determined by cardiopulmonary exercise testing
      following 20 weeks of treatment with omecamtiv mecarbil or placebo
Oversight Authorities:

      United States: Food and Drug Administration Canada: Health Canada France: National Agency for
      the Safety of Medicine and Health Products Germany: Federal Institute for Drugs and Medical
      Devices Hungary: National Institute of Pharmacy and Nutrition Italy: Italian Medicines Agency
      Netherlands: Medicines Evaluation Board Poland: Chief Pharmaceutical Inspectorate Sweden:
      Medical Products Agency
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in Peak Oxygen Uptake on Cardiopulmonary Exercise Testing From Baseline to Week 20
time frame: Baseline and Week 20
description: The effect of treatment on exercise capacity, as assessed by peak oxygen uptake, was assessed during cardiopulmonary exercise testing (CPET) with gas-exchange analysis. Cycle ergometry was the preferred modality for exercise testing; treadmill exercise testing was an acceptable alternative. Participants were to use the same testing modality for all exercise tests during the study. Whenever possible, CPET was administered by the same study personnel using the same equipment throughout the study.
measure: Change in Total Workload During Cardiopulmonary Exercise Testing From Baseline to Week 20
time frame: Baseline and Week 20
description: Total workload was measured during CPET (cycle ergometry [preferred] or treadmill exercise testing) and represents the maximum load to which a participant was subjected during CPET in order to produce work.
measure: Change in Ventilatory Efficiency During Cardiopulmonary Exercise Testing From Baseline to Week 20
time frame: Baseline and Week 20
description: Ventilatory efficiency (ventilation [VE]/volume of exhaled carbon dioxide [VCO2]) was measured through CPET with gas exchange analysis.
measure: Change in the Average Daily Activity Units Measured Over a 2-week Period From Baseline (Week -2 to Day 1) to Weeks 18-20
time frame: Baseline (Week -2 to Day 1) to Weeks 18-20
description: The effect of treatment on daily activity, as assessed by average daily activity units, was evaluated by actigraphy. Actigraphy was collected during 4 sessions throughout the study for 2 week intervals.
arm group label: Omecamtiv Mecarbil
arm group type: Experimental
description: Omecamtiv mecarbil was administered as an oral modified-release tablet twice daily for up to 20 weeks. Participants randomized to this arm started at an omecamtiv mecarbil dose of 25 mg twice daily. The dose could be increased based on plasma concentrations at Weeks 2 and 6.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants randomized this arm received placebo tablets (matching the appearance of the omecamtiv mecarbil tablets) twice daily for up to 20 weeks.
intervention type: Drug
intervention name: Omecamtiv Mecarbil
description: Oral omecamtiv mecarbil twice daily for up to 20 weeks with dose level determined by periodic blood testing
arm group label: Omecamtiv Mecarbil
other name: CK-1827452
other name: AMG-423
intervention type: Drug
intervention name: Placebo
description: Oral placebo twice daily for up to 20 weeks
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Cytokinetics, MD
role: Study Director
affiliation: Cytokinetics
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country: Canada
country: France
country: Germany
country: Hungary
country: Italy
country: Netherlands
country: Poland
country: Sweden
country: United States
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: http://www.amgen.com/datasharing
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certain agreements: 
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