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A Single and Multiple Ascending Dose Study of CK-3773274 in Healthy Adult Subjects

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ClinicalTrials.gov Identifier: NCT03767855
Recruitment Status : Completed
First Posted : December 7, 2018
Last Update Posted : January 29, 2020
Sponsor:
Information provided by (Responsible Party):
Cytokinetics

Study Description
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Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Symptomatic Obstructive Hypertrophic Cardiomyopathy Healthy Subjects Drug: CK-3773274 - Granules in Capsule Drug: Placebo - Granules in Capsule Drug: CK-3773274 - Tablets Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 114 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
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
Actual Study Start Date : December 4, 2018
Actual Primary Completion Date : January 3, 2020
Actual Study Completion Date : January 3, 2020

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Arms and Interventions
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Arm Intervention/treatment
Experimental: CK-3773274 for SAD Cohorts
Subjects will be assigned to one of 8 planned dose cohorts and receive single doses of CK-3773274
 Drug: CK-3773274 - Granules in Capsule
CK-3773274 formulated as granules in capsule
Placebo Comparator: Placebo for SAD Cohorts
Subjects will be assigned to one of 8 planned dose cohorts and receive single doses of placebo
 Drug: Placebo - Granules in Capsule
Placebo formulated as granules in capsule
Experimental: CK-3773274 for MAD Cohorts
Subjects will be assigned to one of 3 planned dose cohorts and receive multiple doses of CK-3773274
 Drug: CK-3773274 - Granules in Capsule
CK-3773274 formulated as granules in capsule
Placebo Comparator: Placebo for MAD Cohorts
Subjects will be assigned to one of 3 planned dose cohorts and receive multiple doses of placebo
 Drug: Placebo - Granules in Capsule
Placebo formulated as granules in capsule
Experimental: CK-3773274 for CYP2D6 Cohort
Subjects with CYP2D6 poor metabolizer phenotype will be assigned to receive a single dose of CK-3773274
 Drug: CK-3773274 - Granules in Capsule
CK-3773274 formulated as granules in capsule
Placebo Comparator: Placebo for CYP2D6 Cohort
Subjects with CYP2D6 poor metabolizer phenotype will be assigned to receive a single dose of placebo
 Drug: Placebo - Granules in Capsule
Placebo formulated as granules in capsule
Experimental: Food Effect
Subjects will be administered CK-3773274 with and without food in a randomized cross-over fashion
 Drug: CK-3773274 - Granules in Capsule
CK-3773274 formulated as granules in capsule
Experimental: Relative Bioavailability
Subjects will be administered CK-3773274 as granules in a capsule and as a tablet in a randomized cross-over fashion.
 Drug: CK-3773274 - Granules in Capsule
CK-3773274 formulated as granules in capsule

Drug: CK-3773274 - Tablets
CK-3773274 formulated as tablets


Outcome Measures
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Primary Outcome Measures :
  1. 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 ]
    Subject incidence of AEs, SAEs, and reduced LVEF


Secondary Outcome Measures :
  1. 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 ]
    Maximum concentration after dosing (Cmax) following single and multiple doses of CK-3773274 administered to healthy subjects

  2. 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 ]
    Changes from baseline in LVEF as measured by echocardiography with doses of CK-3773274

  3. Assess the effect of CYP2D6 genetic variants on the PK of CK-3773274 [ Time Frame: Day -1 - Day 24 ]
    Maximum concentration after dosing (Cmax) following a single dose administered to CYP2D6 poor metabolizers

  4. Assess the effect of a meal on how much CK-3773274 is in the blood in healthy subjects [ Time Frame: Day -1 - Day 24 ]
    Maximum concentration after dosing (Cmax) following single and multiple doses of CK-3773274 administered to healthy subjects in fed and fasted states

  5. 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 ]
    PK parameters such as AUC calculated using plasma concentrations of CK-3773274


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Males and females (of non-childbearing potential) between 18 and 55 years of age, inclusive
  2. Body weight > 55.0 kg and body mass index within 18.0 to 32.0 kg/m2, inclusive
  3. Normal cardiac structure and function, or if abnormalities are present, they are deemed not clinically significant
  4. Normal to high left ventricular ejection fraction.
  5. Normal electrocardiogram (ECG) or, if abnormalities are present, they are deemed not clinically significant
  6. Clinical laboratory findings within normal range
  7. Negative hepatitis panel (including hepatitis B surface antigen and hepatitis C antibody), and negative human immunodeficiency virus antibody screens
  8. Willing and able to refrain from strenuous exercise (eg, activity which could be expected to cause muscle soreness)
  9. For Arms 5 and 6 only: Subject is a CYP2D6 poor metabolizer

Exclusion Criteria:

  1. History of any significant illness or disorder
  2. History of stomach or intestinal surgery or resection (appendectomy, hernia repair, and/or cholecystectomy will be allowed)
  3. A clinically significant illness within 4 weeks of Check-in
  4. Inability to swallow capsules or tablets
  5. History of or current substance abuse (drug or alcohol), known drug or alcohol dependence within the last 2 years prior to Screening, or positive test for drugs of abuse during the screening period
  6. Use of any tobacco-containing or nicotine-containing products within 3 months prior to Check-in
  7. Participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 30 days prior to Check-in
  8. Any blood donation within 60 days of dosing, plasma donation within 30 days of dosing, or receipt of blood products within 2 months prior to Check-in
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03767855


Locations
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United States, Arizona
Clinical Site
Tempe, Arizona, United States, 85283
Sponsors and Collaborators
Cytokinetics
Investigators
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Study Director: Study Director MD Cytokinetics
More Information
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Responsible Party: Cytokinetics
ClinicalTrials.gov Identifier: NCT03767855    
Other Study ID Numbers: CY 6011
First Posted: December 7, 2018    Key Record Dates
Last Update Posted: January 29, 2020
Last Verified: January 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Cytokinetics:
CK-3773274
CK-274
obstructive hypertrophic cardiomyopathy
oHCM
Additional relevant MeSH terms:
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Cardiomyopathies
Cardiomyopathy, Hypertrophic
Hypertrophy
Heart Diseases
Cardiovascular Diseases
 Pathological Conditions, Anatomical
Aortic Stenosis, Subvalvular
Aortic Valve Stenosis
Heart Valve Diseases