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The purposes of this study are to:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CK-3773274 for SAD Cohorts | Experimental | Subjects will be assigned to one of 8 planned dose cohorts and receive single doses of CK-3773274 |
|
| Placebo for SAD Cohorts | Placebo Comparator | Subjects will be assigned to one of 8 planned dose cohorts and receive single doses of placebo |
|
| CK-3773274 for MAD Cohorts | Experimental | Subjects will be assigned to one of 3 planned dose cohorts and receive multiple doses of CK-3773274 |
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| Placebo for MAD Cohorts | Placebo Comparator | Subjects will be assigned to one of 3 planned dose cohorts and receive multiple doses of placebo |
|
| CK-3773274 for CYP2D6 Cohort | Experimental | Subjects with CYP2D6 poor metabolizer phenotype will be assigned to receive a single dose of CK-3773274 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CK-3773274 - Granules in Capsule | Drug | CK-3773274 formulated as granules in capsule |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Adverse events and Safety Signals observed during single and multiple ascending doses of CK-3773274 administered orally to healthy adult subjects. | Subject incidence of AEs, SAEs, and reduced LVEF | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax of CK-3773274 after single and multiple ascending doses | Maximum concentration after dosing (Cmax) following single and multiple doses of CK-3773274 administered to healthy subjects | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Study Director MD | Cytokinetics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Site | Tempe | Arizona | 85283 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36061336 | Derived | Malik FI, Robertson LA, Armas DR, Robbie EP, Osmukhina A, Xu D, Li H, Solomon SD. A Phase 1 Dose-Escalation Study of the Cardiac Myosin Inhibitor Aficamten in Healthy Participants. JACC Basic Transl Sci. 2022 Aug 10;7(8):763-775. doi: 10.1016/j.jacbts.2022.04.008. eCollection 2022 Aug. |
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| ID | Term |
|---|---|
| D002312 | Cardiomyopathy, Hypertrophic |
| ID | Term |
|---|---|
| D009202 | Cardiomyopathies |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D001020 | Aortic Stenosis, Subvalvular |
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| ID | Term |
|---|---|
| D002214 | Capsules |
| ID | Term |
|---|---|
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
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| Placebo for CYP2D6 Cohort |
| Placebo Comparator |
Subjects with CYP2D6 poor metabolizer phenotype will be assigned to receive a single dose of placebo |
|
| Food Effect | Experimental | Subjects will be administered CK-3773274 with and without food in a randomized cross-over fashion |
|
| Relative Bioavailability | Experimental | Subjects will be administered CK-3773274 as granules in a capsule and as a tablet in a randomized cross-over fashion. |
|
| Placebo - Granules in Capsule | Drug | Placebo formulated as granules in capsule |
|
| CK-3773274 - Tablets | Drug | CK-3773274 formulated as tablets |
|
| Change in absolute reduction in ejection fraction relative to baseline with doses of CK-3773274 |
Changes from baseline in LVEF as measured by echocardiography 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 |
| Assess the effect of CYP2D6 genetic variants on the PK of CK-3773274 | Maximum concentration after dosing (Cmax) following a single dose administered to CYP2D6 poor metabolizers | Day -1 - Day 24 |
| Assess the effect of a meal on how much CK-3773274 is in the blood in healthy subjects | Maximum concentration after dosing (Cmax) following single and multiple doses of CK-3773274 administered to healthy subjects in fed and fasted states | Day -1 - Day 24 |
| Relative bioavailability of CK-3773274 formulated as granules in capsule versus a tablet in healthy adult subjects | PK parameters such as AUC calculated using plasma concentrations of CK-3773274 | Time Frame for Bioavailability Cohort: Day -1 - Day 29 |
| D001024 |
| Aortic Valve Stenosis |
| D000082862 | Aortic Valve Disease |
| D006349 | Heart Valve Diseases |