Back to resultsA Single and Multiple Ascending Dose Study of CK-3773274 in Healthy Adult Subjects
Primary Purpose
Symptomatic Obstructive Hypertrophic Cardiomyopathy, Healthy Subjects
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CK-3773274 - Granules in Capsule
Placebo - Granules in Capsule
CK-3773274 - Tablets
Sponsored by
About this trial
This is an interventional basic science trial for Symptomatic Obstructive Hypertrophic Cardiomyopathy focused on measuring CK-3773274, CK-274, obstructive hypertrophic cardiomyopathy, oHCM
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Sites / Locations
- Clinical Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm Type
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Experimental
Arm Label
CK-3773274 for SAD Cohorts
Placebo for SAD Cohorts
CK-3773274 for MAD Cohorts
Placebo for MAD Cohorts
CK-3773274 for CYP2D6 Cohort
Placebo for CYP2D6 Cohort
Food Effect
Relative Bioavailability
Arm Description
Subjects will be assigned to one of 8 planned dose cohorts and receive single doses of CK-3773274
Subjects will be assigned to one of 8 planned dose cohorts and receive single doses of placebo
Subjects will be assigned to one of 3 planned dose cohorts and receive multiple doses of CK-3773274
Subjects will be assigned to one of 3 planned dose cohorts and receive multiple doses of placebo
Subjects with CYP2D6 poor metabolizer phenotype will be assigned to receive a single dose of CK-3773274
Subjects with CYP2D6 poor metabolizer phenotype will be assigned to receive a single dose of placebo
Subjects will be administered CK-3773274 with and without food in a randomized cross-over fashion
Subjects will be administered CK-3773274 as granules in a capsule and as a tablet in a randomized cross-over fashion.
Outcomes
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.
Subject incidence of AEs, SAEs, and reduced LVEF
Secondary Outcome Measures
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
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
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
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
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03767855
Brief Title
A Single and Multiple Ascending Dose Study of CK-3773274 in Healthy Adult Subjects
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
December 4, 2018 (Actual)
Primary Completion Date
January 3, 2020 (Actual)
Study Completion Date
January 3, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cytokinetics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purposes of this study are to:
Learn about the safety of CK-3773274 after a single dose and multiple doses in healthy subjects.
Learn how healthy subjects tolerate CK-3773274 after a single dose and multiple doses.
Find out how much CK-3773274 is in the blood after a single dose and multiple doses.
Determine the effect of doses of CK-3773274 on the pumping function of the heart.
Evaluate the effect of cytochrome genetic variants on how the body metabolizes CK-3773274.
Evaluate the effect of a meal on how much CK-3773274 is in the blood in healthy adult subjects.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Symptomatic Obstructive Hypertrophic Cardiomyopathy, Healthy Subjects
Keywords
CK-3773274, CK-274, obstructive hypertrophic cardiomyopathy, oHCM
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
114 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CK-3773274 for SAD Cohorts
Arm Type
Experimental
Arm Description
Subjects will be assigned to one of 8 planned dose cohorts and receive single doses of CK-3773274
Arm Title
Placebo for SAD Cohorts
Arm Type
Placebo Comparator
Arm Description
Subjects will be assigned to one of 8 planned dose cohorts and receive single doses of placebo
Arm Title
CK-3773274 for MAD Cohorts
Arm Type
Experimental
Arm Description
Subjects will be assigned to one of 3 planned dose cohorts and receive multiple doses of CK-3773274
Arm Title
Placebo for MAD Cohorts
Arm Type
Placebo Comparator
Arm Description
Subjects will be assigned to one of 3 planned dose cohorts and receive multiple doses of placebo
Arm Title
CK-3773274 for CYP2D6 Cohort
Arm Type
Experimental
Arm Description
Subjects with CYP2D6 poor metabolizer phenotype will be assigned to receive a single dose of CK-3773274
Arm Title
Placebo for CYP2D6 Cohort
Arm Type
Placebo Comparator
Arm Description
Subjects with CYP2D6 poor metabolizer phenotype will be assigned to receive a single dose of placebo
Arm Title
Food Effect
Arm Type
Experimental
Arm Description
Subjects will be administered CK-3773274 with and without food in a randomized cross-over fashion
Arm Title
Relative Bioavailability
Arm Type
Experimental
Arm Description
Subjects will be administered CK-3773274 as granules in a capsule and as a tablet in a randomized cross-over fashion.
Intervention Type
Drug
Intervention Name(s)
CK-3773274 - Granules in Capsule
Intervention Description
CK-3773274 formulated as granules in capsule
Intervention Type
Drug
Intervention Name(s)
Placebo - Granules in Capsule
Intervention Description
Placebo formulated as granules in capsule
Intervention Type
Drug
Intervention Name(s)
CK-3773274 - Tablets
Intervention Description
CK-3773274 formulated as tablets
Primary Outcome Measure Information:
Title
Incidence of Adverse events and Safety Signals observed during single and multiple ascending doses of CK-3773274 administered orally to healthy adult subjects.
Description
Subject incidence of AEs, SAEs, and reduced LVEF
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
Secondary Outcome Measure Information:
Title
Cmax of CK-3773274 after single and multiple ascending doses
Description
Maximum concentration after dosing (Cmax) following single and multiple doses of CK-3773274 administered to healthy subjects
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
Title
Change in absolute reduction in ejection fraction relative to baseline with doses of CK-3773274
Description
Changes from baseline in LVEF as measured by echocardiography 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
Title
Assess the effect of CYP2D6 genetic variants on the PK of CK-3773274
Description
Maximum concentration after dosing (Cmax) following a single dose administered to CYP2D6 poor metabolizers
Time Frame
Day -1 - Day 24
Title
Assess the effect of a meal on how much CK-3773274 is in the blood in healthy subjects
Description
Maximum concentration after dosing (Cmax) following single and multiple doses of CK-3773274 administered to healthy subjects in fed and fasted states
Time Frame
Day -1 - Day 24
Title
Relative bioavailability of CK-3773274 formulated as granules in capsule versus a tablet in healthy adult subjects
Description
PK parameters such as AUC calculated using plasma concentrations of CK-3773274
Time Frame
Time Frame for Bioavailability Cohort: Day -1 - Day 29
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director MD
Organizational Affiliation
Cytokinetics
Official's Role
Study Director
Facility Information:
Facility Name
Clinical Site
City
Tempe
State/Province
Arizona
ZIP/Postal Code
85283
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
36061336
Citation
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.
Results Reference
derived
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A Single and Multiple Ascending Dose Study of CK-3773274 in Healthy Adult Subjects
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