A Single and Multiple Ascending Dose Study of CK-3773274 in Healthy Adult Subjects
Study Details
Study Description
Brief Summary
The purposes of this study are to:
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Learn about the safety of CK-3773274 after a single dose and multiple doses in healthy subjects.
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Learn how healthy subjects tolerate CK-3773274 after a single dose and multiple doses.
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Find out how much CK-3773274 is in the blood after a single dose and multiple doses.
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Determine the effect of doses of CK-3773274 on the pumping function of the heart.
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Evaluate the effect of cytochrome genetic variants on how the body metabolizes CK-3773274.
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Evaluate the effect of a meal on how much CK-3773274 is in the blood in healthy adult subjects.
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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 |
---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
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
Primary Outcome Measures
- Incidence of Adverse events and Safety Signals observed during single and multiple ascending doses of CK-3773274 administered orally to healthy adult subjects. [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
- Cmax of CK-3773274 after single and multiple ascending doses [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
- Change in absolute reduction in ejection fraction relative to baseline with doses of CK-3773274 [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
- Assess the effect of CYP2D6 genetic variants on the PK of CK-3773274 [Day -1 - Day 24]
Maximum concentration after dosing (Cmax) following a single dose administered to CYP2D6 poor metabolizers
- Assess the effect of a meal on how much CK-3773274 is in the blood in healthy subjects [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
- Relative bioavailability of CK-3773274 formulated as granules in capsule versus a tablet in healthy adult subjects [Time Frame for Bioavailability Cohort: Day -1 - Day 29]
PK parameters such as AUC calculated using plasma concentrations of CK-3773274
Eligibility Criteria
Criteria
Inclusion Criteria:
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Males and females (of non-childbearing potential) between 18 and 55 years of age, inclusive
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Body weight > 55.0 kg and body mass index within 18.0 to 32.0 kg/m2, inclusive
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Normal cardiac structure and function, or if abnormalities are present, they are deemed not clinically significant
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Normal to high left ventricular ejection fraction.
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Normal electrocardiogram (ECG) or, if abnormalities are present, they are deemed not clinically significant
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Clinical laboratory findings within normal range
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Negative hepatitis panel (including hepatitis B surface antigen and hepatitis C antibody), and negative human immunodeficiency virus antibody screens
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Willing and able to refrain from strenuous exercise (eg, activity which could be expected to cause muscle soreness)
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For Arms 5 and 6 only: Subject is a CYP2D6 poor metabolizer
Exclusion Criteria:
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History of any significant illness or disorder
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History of stomach or intestinal surgery or resection (appendectomy, hernia repair, and/or cholecystectomy will be allowed)
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A clinically significant illness within 4 weeks of Check-in
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Inability to swallow capsules or tablets
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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
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Use of any tobacco-containing or nicotine-containing products within 3 months prior to Check-in
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Participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 30 days prior to Check-in
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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
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Clinical Site | Tempe | Arizona | United States | 85283 |
Sponsors and Collaborators
- Cytokinetics
Investigators
- Study Director: Study Director MD, Cytokinetics
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CY 6011