Clinical trial NCT03767855: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Symptomatic Obstructive Hypertrophic Cardiomyopathy
Healthy Subjects
Keywords: CK-3773274
CK-274
obstructive hypertrophic cardiomyopathy
oHCM
aficamten
Lead sponsor: Cytokinetics
Sponsor class: INDUSTRY
First posted: 2018-12-07
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Adverse events and Safety Signals observed during single and multiple ascending doses of CK-3773274 administered orally to healthy adult subjects.
timeFrame: 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 outcomes:
measure: Cmax of CK-3773274 after single and multiple ascending doses
timeFrame: 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
measure: Change in absolute reduction in ejection fraction relative to baseline with doses of CK-3773274
timeFrame: 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
measure: Assess the effect of CYP2D6 genetic variants on the PK of CK-3773274
timeFrame: Day -1 - Day 24
measure: Assess the effect of a meal on how much CK-3773274 is in the blood in healthy subjects
timeFrame: Day -1 - Day 24
measure: Relative bioavailability of CK-3773274 formulated as granules in capsule versus a tablet in healthy adult subjects
timeFrame: Time Frame for Bioavailability Cohort: Day -1 - Day 29
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Clinical Site
state: Arizona
Study officials:
affiliation: Cytokinetics
name: Study Director MD
role: STUDY_DIRECTOR
References:
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.