<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/NCT03767855</url>
  </required_header>
  <id_info>
    <org_study_id>CY 6011</org_study_id>
    <nct_id>NCT03767855</nct_id>
  </id_info>
  <brief_title>A Single and Multiple Ascending Dose Study of CK-3773274 in Healthy Adult Subjects</brief_title>
  <official_title>A Phase 1, Double-Blind, Randomized, Placebo-Controlled, Multi-Part, Single and Multiple Ascending Dose Study of CK-3773274 in Healthy Adult Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cytokinetics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cytokinetics</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purposes of this study are to:&#xD;
&#xD;
        1. Learn about the safety of CK-3773274 after a single dose and multiple doses in healthy&#xD;
           subjects.&#xD;
&#xD;
        2. Learn how healthy subjects tolerate CK-3773274 after a single dose and multiple doses.&#xD;
&#xD;
        3. Find out how much CK-3773274 is in the blood after a single dose and multiple doses.&#xD;
&#xD;
        4. Determine the effect of doses of CK-3773274 on the pumping function of the heart.&#xD;
&#xD;
        5. Evaluate the effect of cytochrome genetic variants on how the body metabolizes&#xD;
           CK-3773274.&#xD;
&#xD;
        6. Evaluate the effect of a meal on how much CK-3773274 is in the blood in healthy adult&#xD;
           subjects.&#xD;
&#xD;
        7. Evaluate whether the amount of CK-3773274 in the blood is the similar for both the&#xD;
           tablet and granules in capsule forms of the drug.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 4, 2018</start_date>
  <completion_date type="Actual">January 3, 2020</completion_date>
  <primary_completion_date type="Actual">January 3, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of Adverse events and Safety Signals observed during single and multiple ascending doses of CK-3773274 administered orally to healthy adult subjects.</measure>
    <time_frame>SAD Cohorts: Day -1 - Day 10; CYP2D6 Cohort: Day -1 - Day - 24; MAD Cohorts: Day -1 - Day 27; Food Effect Cohort: Day -1 - Day 24; relative Bioavailability Cohort: Day -1 - Day 29</time_frame>
    <description>Subject incidence of AEs, SAEs, and reduced LVEF</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cmax of CK-3773274 after single and multiple ascending doses</measure>
    <time_frame>SAD Cohorts: Day 1; CYP2D6 Cohort: Day 1; MAD Cohorts: Day 14 or Day 17; Food Effect Cohort: Day 15; Relative Bioavailability Cohort: Day 15</time_frame>
    <description>Maximum concentration after dosing (Cmax) following single and multiple doses of CK-3773274 administered to healthy subjects</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in absolute reduction in ejection fraction relative to baseline with doses of CK-3773274</measure>
    <time_frame>Time Frame for SAD Cohorts: Day -1 - Day 10; Time Frame for CYP2D6 Cohort: Day -1 - Day 24; Time Frame for MAD Cohorts: Day -1 - Day 27</time_frame>
    <description>Changes from baseline in LVEF as measured by echocardiography with doses of CK-3773274</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess the effect of CYP2D6 genetic variants on the PK of CK-3773274</measure>
    <time_frame>Day -1 - Day 24</time_frame>
    <description>Maximum concentration after dosing (Cmax) following a single dose administered to CYP2D6 poor metabolizers</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess the effect of a meal on how much CK-3773274 is in the blood in healthy subjects</measure>
    <time_frame>Day -1 - Day 24</time_frame>
    <description>Maximum concentration after dosing (Cmax) following single and multiple doses of CK-3773274 administered to healthy subjects in fed and fasted states</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relative bioavailability of CK-3773274 formulated as granules in capsule versus a tablet in healthy adult subjects</measure>
    <time_frame>Time Frame for Bioavailability Cohort: Day -1 - Day 29</time_frame>
    <description>PK parameters such as AUC calculated using plasma concentrations of CK-3773274</description>
  </secondary_outcome>
  <number_of_arms>8</number_of_arms>
  <enrollment type="Actual">114</enrollment>
  <condition>Symptomatic Obstructive Hypertrophic Cardiomyopathy</condition>
  <condition>Healthy Subjects</condition>
  <arm_group>
    <arm_group_label>CK-3773274 for SAD Cohorts</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will be assigned to one of 8 planned dose cohorts and receive single doses of CK-3773274</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo for SAD Cohorts</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects will be assigned to one of 8 planned dose cohorts and receive single doses of placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CK-3773274 for MAD Cohorts</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will be assigned to one of 3 planned dose cohorts and receive multiple doses of CK-3773274</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo for MAD Cohorts</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects will be assigned to one of 3 planned dose cohorts and receive multiple doses of placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CK-3773274 for CYP2D6 Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects with CYP2D6 poor metabolizer phenotype will be assigned to receive a single dose of CK-3773274</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo for CYP2D6 Cohort</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects with CYP2D6 poor metabolizer phenotype will be assigned to receive a single dose of placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Food Effect</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will be administered CK-3773274 with and without food in a randomized cross-over fashion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Relative Bioavailability</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will be administered CK-3773274 as granules in a capsule and as a tablet in a randomized cross-over fashion.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CK-3773274 - Granules in Capsule</intervention_name>
    <description>CK-3773274 formulated as granules in capsule</description>
    <arm_group_label>CK-3773274 for CYP2D6 Cohort</arm_group_label>
    <arm_group_label>CK-3773274 for MAD Cohorts</arm_group_label>
    <arm_group_label>CK-3773274 for SAD Cohorts</arm_group_label>
    <arm_group_label>Food Effect</arm_group_label>
    <arm_group_label>Relative Bioavailability</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo - Granules in Capsule</intervention_name>
    <description>Placebo formulated as granules in capsule</description>
    <arm_group_label>Placebo for CYP2D6 Cohort</arm_group_label>
    <arm_group_label>Placebo for MAD Cohorts</arm_group_label>
    <arm_group_label>Placebo for SAD Cohorts</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CK-3773274 - Tablets</intervention_name>
    <description>CK-3773274 formulated as tablets</description>
    <arm_group_label>Relative Bioavailability</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males and females (of non-childbearing potential) between 18 and 55 years of age,&#xD;
             inclusive&#xD;
&#xD;
          2. Body weight &gt; 55.0 kg and body mass index within 18.0 to 32.0 kg/m2, inclusive&#xD;
&#xD;
          3. Normal cardiac structure and function, or if abnormalities are present, they are&#xD;
             deemed not clinically significant&#xD;
&#xD;
          4. Normal to high left ventricular ejection fraction.&#xD;
&#xD;
          5. Normal electrocardiogram (ECG) or, if abnormalities are present, they are deemed not&#xD;
             clinically significant&#xD;
&#xD;
          6. Clinical laboratory findings within normal range&#xD;
&#xD;
          7. Negative hepatitis panel (including hepatitis B surface antigen and hepatitis C&#xD;
             antibody), and negative human immunodeficiency virus antibody screens&#xD;
&#xD;
          8. Willing and able to refrain from strenuous exercise (eg, activity which could be&#xD;
             expected to cause muscle soreness)&#xD;
&#xD;
          9. For Arms 5 and 6 only: Subject is a CYP2D6 poor metabolizer&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of any significant illness or disorder&#xD;
&#xD;
          2. History of stomach or intestinal surgery or resection (appendectomy, hernia repair,&#xD;
             and/or cholecystectomy will be allowed)&#xD;
&#xD;
          3. A clinically significant illness within 4 weeks of Check-in&#xD;
&#xD;
          4. Inability to swallow capsules or tablets&#xD;
&#xD;
          5. History of or current substance abuse (drug or alcohol), known drug or alcohol&#xD;
             dependence within the last 2 years prior to Screening, or positive test for drugs of&#xD;
             abuse during the screening period&#xD;
&#xD;
          6. Use of any tobacco-containing or nicotine-containing products within 3 months prior to&#xD;
             Check-in&#xD;
&#xD;
          7. Participation in any other investigational study drug trial in which receipt of an&#xD;
             investigational study drug occurred within 30 days prior to Check-in&#xD;
&#xD;
          8. Any blood donation within 60 days of dosing, plasma donation within 30 days of dosing,&#xD;
             or receipt of blood products within 2 months prior to Check-in&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Study Director MD</last_name>
    <role>Study Director</role>
    <affiliation>Cytokinetics</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Tempe</city>
        <state>Arizona</state>
        <zip>85283</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>December 3, 2018</study_first_submitted>
  <study_first_submitted_qc>December 5, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 7, 2018</study_first_posted>
  <last_update_submitted>January 28, 2020</last_update_submitted>
  <last_update_submitted_qc>January 28, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 29, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CK-3773274</keyword>
  <keyword>CK-274</keyword>
  <keyword>obstructive hypertrophic cardiomyopathy</keyword>
  <keyword>oHCM</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cardiomyopathies</mesh_term>
    <mesh_term>Cardiomyopathy, Hypertrophic</mesh_term>
    <mesh_term>Hypertrophy</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03767855
org study id: CY 6011
nct id: NCT03767855
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purposes of this study are to:

        1. Learn about the safety of CK-3773274 after a single dose and multiple doses in healthy
           subjects.

        2. Learn how healthy subjects tolerate CK-3773274 after a single dose and multiple doses.

        3. Find out how much CK-3773274 is in the blood after a single dose and multiple doses.

        4. Determine the effect of doses of CK-3773274 on the pumping function of the heart.

        5. Evaluate the effect of cytochrome genetic variants on how the body metabolizes
           CK-3773274.

        6. Evaluate the effect of a meal on how much CK-3773274 is in the blood in healthy adult
           subjects.

        7. Evaluate whether the amount of CK-3773274 in the blood is the similar for both the
           tablet and granules in capsule forms of the drug.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Basic Science
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Incidence of Adverse events and Safety Signals observed during single and multiple ascending doses of CK-3773274 administered orally to healthy adult subjects.
time frame: SAD Cohorts: Day -1 - Day 10; CYP2D6 Cohort: Day -1 - Day - 24; MAD Cohorts: Day -1 - Day 27; Food Effect Cohort: Day -1 - Day 24; relative Bioavailability Cohort: Day -1 - Day 29
description: Subject incidence of AEs, SAEs, and reduced LVEF
measure: Cmax of CK-3773274 after single and multiple ascending doses
time frame: SAD Cohorts: Day 1; CYP2D6 Cohort: Day 1; MAD Cohorts: Day 14 or Day 17; Food Effect Cohort: Day 15; Relative Bioavailability Cohort: Day 15
description: Maximum concentration after dosing (Cmax) following single and multiple doses of CK-3773274 administered to healthy subjects
measure: Change in absolute reduction in ejection fraction relative to baseline with doses of CK-3773274
time frame: Time Frame for SAD Cohorts: Day -1 - Day 10; Time Frame for CYP2D6 Cohort: Day -1 - Day 24; Time Frame for MAD Cohorts: Day -1 - Day 27
description: Changes from baseline in LVEF as measured by echocardiography with doses of CK-3773274
measure: Assess the effect of CYP2D6 genetic variants on the PK of CK-3773274
time frame: Day -1 - Day 24
description: Maximum concentration after dosing (Cmax) following a single dose administered to CYP2D6 poor metabolizers
measure: Assess the effect of a meal on how much CK-3773274 is in the blood in healthy subjects
time frame: Day -1 - Day 24
description: Maximum concentration after dosing (Cmax) following single and multiple doses of CK-3773274 administered to healthy subjects in fed and fasted states
measure: Relative bioavailability of CK-3773274 formulated as granules in capsule versus a tablet in healthy adult subjects
time frame: Time Frame for Bioavailability Cohort: Day -1 - Day 29
description: PK parameters such as AUC calculated using plasma concentrations of CK-3773274
arm group label: CK-3773274 for SAD Cohorts
arm group type: Experimental
description: Subjects will be assigned to one of 8 planned dose cohorts and receive single doses of CK-3773274
arm group label: Placebo for SAD Cohorts
arm group type: Placebo Comparator
description: Subjects will be assigned to one of 8 planned dose cohorts and receive single doses of placebo
arm group label: CK-3773274 for MAD Cohorts
arm group type: Experimental
description: Subjects will be assigned to one of 3 planned dose cohorts and receive multiple doses of CK-3773274
arm group label: Placebo for MAD Cohorts
arm group type: Placebo Comparator
description: Subjects will be assigned to one of 3 planned dose cohorts and receive multiple doses of placebo
arm group label: CK-3773274 for CYP2D6 Cohort
arm group type: Experimental
description: Subjects with CYP2D6 poor metabolizer phenotype will be assigned to receive a single dose of CK-3773274
arm group label: Placebo for CYP2D6 Cohort
arm group type: Placebo Comparator
description: Subjects with CYP2D6 poor metabolizer phenotype will be assigned to receive a single dose of placebo
arm group label: Food Effect
arm group type: Experimental
description: Subjects will be administered CK-3773274 with and without food in a randomized cross-over fashion
arm group label: Relative Bioavailability
arm group type: Experimental
description: Subjects will be administered CK-3773274 as granules in a capsule and as a tablet in a randomized cross-over fashion.
intervention type: Drug
intervention name: CK-3773274 - Granules in Capsule
description: CK-3773274 formulated as granules in capsule
arm group label: CK-3773274 for CYP2D6 Cohort
arm group label: CK-3773274 for MAD Cohorts
arm group label: CK-3773274 for SAD Cohorts
arm group label: Food Effect
arm group label: Relative Bioavailability
intervention type: Drug
intervention name: Placebo - Granules in Capsule
description: Placebo formulated as granules in capsule
arm group label: Placebo for CYP2D6 Cohort
arm group label: Placebo for MAD Cohorts
arm group label: Placebo for SAD Cohorts
intervention type: Drug
intervention name: CK-3773274 - Tablets
description: CK-3773274 formulated as tablets
arm group label: Relative Bioavailability
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Study Director MD
role: Study Director
affiliation: Cytokinetics
facility: 
country: United States
responsible party type: Sponsor
mesh term: Cardiomyopathies
mesh term: Cardiomyopathy, Hypertrophic
mesh term: Hypertrophy