A Single and Multiple Ascending Dose Study of CK-3773274 in Healthy Adult Subjects
- Conditions
- Healthy SubjectsSymptomatic Obstructive Hypertrophic Cardiomyopathy
- Interventions
- Drug: Placebo - Granules in CapsuleDrug: CK-3773274 - Granules in CapsuleDrug: CK-3773274 - Tablets
- Registration Number
- NCT03767855
- Lead Sponsor
- Cytokinetics
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 114
- Males and females (of non-childbearing potential) between 18 and 55 years of age, inclusive
- Body weight > 55.0 kg and body mass index within 18.0 to 32.0 kg/m2, inclusive
- Normal cardiac structure and function, or if abnormalities are present, they are deemed not clinically significant
- Normal to high left ventricular ejection fraction.
- Normal electrocardiogram (ECG) or, if abnormalities are present, they are deemed not clinically significant
- Clinical laboratory findings within normal range
- Negative hepatitis panel (including hepatitis B surface antigen and hepatitis C antibody), and negative human immunodeficiency virus antibody screens
- Willing and able to refrain from strenuous exercise (eg, activity which could be expected to cause muscle soreness)
- For Arms 5 and 6 only: Subject is a CYP2D6 poor metabolizer
- History of any significant illness or disorder
- History of stomach or intestinal surgery or resection (appendectomy, hernia repair, and/or cholecystectomy will be allowed)
- A clinically significant illness within 4 weeks of Check-in
- Inability to swallow capsules or tablets
- 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
- Use of any tobacco-containing or nicotine-containing products within 3 months prior to Check-in
- Participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 30 days prior to Check-in
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Placebo for SAD Cohorts Placebo - Granules in Capsule Subjects will be assigned to one of 8 planned dose cohorts and receive single doses of placebo CK-3773274 for MAD Cohorts CK-3773274 - Granules in Capsule Subjects will be assigned to one of 3 planned dose cohorts and receive multiple doses of CK-3773274 Placebo for MAD Cohorts Placebo - Granules in Capsule Subjects will be assigned to one of 3 planned dose cohorts and receive multiple doses of placebo CK-3773274 for CYP2D6 Cohort CK-3773274 - Granules in Capsule Subjects with CYP2D6 poor metabolizer phenotype will be assigned to receive a single dose of CK-3773274 Placebo for CYP2D6 Cohort Placebo - Granules in Capsule Subjects with CYP2D6 poor metabolizer phenotype will be assigned to receive a single dose of placebo Food Effect CK-3773274 - Granules in Capsule Subjects will be administered CK-3773274 with and without food in a randomized cross-over fashion Relative Bioavailability CK-3773274 - Granules in Capsule Subjects will be administered CK-3773274 as granules in a capsule and as a tablet in a randomized cross-over fashion. Relative Bioavailability CK-3773274 - Tablets Subjects will be administered CK-3773274 as granules in a capsule and as a tablet in a randomized cross-over fashion. CK-3773274 for SAD Cohorts CK-3773274 - Granules in Capsule Subjects will be assigned to one of 8 planned dose cohorts and receive single doses of CK-3773274
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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
Trial Locations
- Locations (1)
Clinical Site
🇺🇸Tempe, Arizona, United States