A Single and Multiple Ascending Dose Study of CK-3773274 in Healthy Adult Subjects

NCT03767855 | Completed Phase 1 FDA Drug

• 1 other identifier: CY 6011
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 1

Brief Summary

The purposes of this study are to:

1. 1.Learn about the safety of CK-3773274 after a single dose and multiple doses in healthy subjects.
2. 2.Learn how healthy subjects tolerate CK-3773274 after a single dose and multiple doses.
3. 3.Find out how much CK-3773274 is in the blood after a single dose and multiple doses.
4. 4.Determine the effect of doses of CK-3773274 on the pumping function of the heart.
5. 5.Evaluate the effect of cytochrome genetic variants on how the body metabolizes CK-3773274.
6. 6.Evaluate the effect of a meal on how much CK-3773274 is in the blood in healthy adult subjects.
7. 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.

Conditions

Symptomatic Obstructive Hypertrophic Cardiomyopathy; Healthy Subjects

Keywords

CK-3773274; CK-274; obstructive hypertrophic cardiomyopathy; oHCM; aficamten

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (5)

• 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

• 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

• Assess the effect of CYP2D6 genetic variants on the PK of CK-3773274

  Day -1 - Day 24

• Assess the effect of a meal on how much CK-3773274 is in the blood in healthy subjects

  Day -1 - Day 24

• 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

Study Arms (8)

CK-3773274 for SAD Cohorts

EXPERIMENTAL

Subjects will be assigned to one of 8 planned dose cohorts and receive single doses of CK-3773274

Drug: CK-3773274 - Granules in Capsule

Placebo for SAD Cohorts

PLACEBO COMPARATOR

Subjects will be assigned to one of 8 planned dose cohorts and receive single doses of placebo

Drug: Placebo - Granules in Capsule

CK-3773274 for MAD Cohorts

EXPERIMENTAL

Subjects will be assigned to one of 3 planned dose cohorts and receive multiple doses of CK-3773274

Drug: CK-3773274 - Granules in Capsule

Placebo for MAD Cohorts

PLACEBO COMPARATOR

Subjects will be assigned to one of 3 planned dose cohorts and receive multiple doses of placebo

Drug: Placebo - Granules in Capsule

CK-3773274 for CYP2D6 Cohort

EXPERIMENTAL

Subjects with CYP2D6 poor metabolizer phenotype will be assigned to receive a single dose of CK-3773274

Drug: CK-3773274 - Granules in Capsule

Placebo for CYP2D6 Cohort

PLACEBO COMPARATOR

Subjects with CYP2D6 poor metabolizer phenotype will be assigned to receive a single dose of placebo

Drug: Placebo - Granules in Capsule

Food Effect

EXPERIMENTAL

Subjects will be administered CK-3773274 with and without food in a randomized cross-over fashion

Drug: CK-3773274 - Granules in Capsule

Relative Bioavailability

EXPERIMENTAL

Subjects will be administered CK-3773274 as granules in a capsule and as a tablet in a randomized cross-over fashion.

Drug: CK-3773274 - Granules in Capsule; Drug: CK-3773274 - Tablets

Interventions

CK-3773274 - Granules in Capsule DRUG

CK-3773274 formulated as granules in capsule

CK-3773274 for CYP2D6 Cohort; CK-3773274 for MAD Cohorts; CK-3773274 for SAD Cohorts; Food Effect; Relative Bioavailability

Placebo - Granules in Capsule DRUG

Placebo formulated as granules in capsule

Placebo for CYP2D6 Cohort; Placebo for MAD Cohorts; Placebo for SAD Cohorts

CK-3773274 - Tablets DRUG

CK-3773274 formulated as tablets

Relative Bioavailability

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Cytokinetics: lead

Study Sites (1)

Clinical Site

Tempe, Arizona, 85283, United States

Location

Related Publications (1)

• 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.

  PMID: 36061336 DERIVED

MeSH Terms

Conditions

Cardiomyopathy, Hypertrophic

Interventions

Capsules

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Officials

• Study Director MD

  Cytokinetics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2018
• First Posted: December 7, 2018
• Study Start: December 4, 2018
• Primary Completion: January 3, 2020
• Study Completion: January 3, 2020
• Last Updated: January 24, 2025

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)