Healthy Subjects, Symptomatic Obstructive Hypertrophic Cardiomyopathy
Conditions
Keywords
CK-3773274, CK-274, obstructive hypertrophic cardiomyopathy, oHCM, aficamten
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.
Interventions
DRUGCK-3773274 - Granules in Capsule
CK-3773274 formulated as granules in capsule
DRUGPlacebo - Granules in Capsule
Placebo formulated as granules in capsule
DRUGCK-3773274 - Tablets
CK-3773274 formulated as tablets
Sponsors
Cytokinetics
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Outcome results
None listed