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CK-4021586

Phase 2

Symptomatic Heart Failure With Preserved Ejection Fraction (HFpEF) | Small molecule | Cardiovascular |Cytokinetics, Incorporated|Last Updated: Aug 27, 2026

Target and mechanism

Molecular targetcardiac myosin
Target classProtein
ModalitySmall molecule

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLED
Total Trials1
Total Enrollment60

FDA Designations

No designations recorded

Clinical trial landscape

CK-4021586 · 2 trials · 2 indications

Phase 2 1Phase 1 1
NCT06793371AMBER-HFpEF: Assessment of CK-4021586 in a Multi-Center, Blinded Evaluation of Safety and Tolerability Results in HFpEFSymptomatic Heart Failure With Preserved Ejection Fraction (HFpEF)
RECRUITING60 Analytics
PHASE2RECRUITING
AMBER-HFpEF: Assessment of CK-4021586 in a Multi-Center, Blinded Evaluation of Safety and Tolerability Results in HFpEF
Symptomatic Heart Failure With Preserved Ejection Fraction (HFpEF)Unlock trial analytics

Study Endpoints

Primary Endpoints

Incidence of early drug discontinuation
12 weeks

Incidence of early drug discontinuation observed during dosing of CK 4021586 in patients with HFpEF

Incidence of LVEF < 40%
12 weeks

Incidence of left-ventricular ejection fraction (LVEF) \< 40% observed during dosing of CK-4021586 in patients with HFpEF

Incidence of AEs
12 weeks

Incidence of adverse events observed during dosing of CK-4021586 in patients with HFpEF

Incidence and severity of AEs
Time Frame for SAD Cohorts: Day -1 - Day 7; Time Frame for MAD Cohorts: Day -1 - Day 14; Time Frame for Food Effect Cohorts: Days 1 to 7 (Treatment Periods 1 and 2)

To assess the safety and tolerability of CK-4021586 when administered orally as single or multiple doses to healthy participants

Secondary Endpoints

Change in NT-proBNP
Baseline to Week 6 and Week 12
Plasma concentrations of CK-4021586
12 weeks
Concentration-response relationship of CK-4021586 on NT-proBNP change
Baseline to Week 12
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Study Design & Arms

AllocationRANDOMIZED
MaskingTRIPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
CK-4021586 - Cohort 1EXPERIMENTALParticipants may receive 150 mg or 300 mg of CK-4021586 daily, guided by echocardiography assessments, for 12 weeks total.
Placebo - Cohort 1PLACEBO_COMPARATORParticipants will receive placebo daily for up to 12 weeks.
CK-4021586 - Cohort 2EXPERIMENTALParticipants may receive 300 mg or 450 mg of CK-4021586 daily, guided by echocardiography assessments, for 12 weeks total.
Placebo - Cohort 2PLACEBO_COMPARATORParticipants will receive placebo daily for up to 12 weeks.
CK-4021586 - Cohort 3EXPERIMENTALParticipants may receive 450 mg or 600 mg of CK-4021586 daily, guided by echocardiography assessments, for 12 weeks total.
Placebo - Cohort 3PLACEBO_COMPARATORParticipants will receive placebo daily for up to 12 weeks.
CK-4021586 for SAD CohortEXPERIMENTALSubjects will be assigned to one of 8 planned dose cohorts and receive single doses of CK-4021586
Placebo for SAD CohortPLACEBO_COMPARATORSubjects will be assigned to one of approximately 8 planned cohorts and receive single doses of placebo
CK-4021586 for MAD CohortEXPERIMENTALSubjects will be assigned to one of 4 planned dose cohorts and receive multiple doses of CK-4021586
Placebo for MAD CohortPLACEBO_COMPARATORSubjects will be assigned to one of approximately 4 planned cohorts and receive multiple of placebo
Food EffectEXPERIMENTALHealthy subjects will be administered CK-4021586 with and without food in a cross-over fashion

Interventions

NameTypeDescription
CK-4021586 (150 mg, 300 mg, 450 mg, and 600 mg)DRUGCK-4021586 administered orally
Placebo to match CK-4021586DRUGPlacebo administered orally
CK-4021586DRUGCK-4021586
Placebo for CK-4021586DRUGPlacebo for CK-4021586
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Eligibility Criteria

Age Range40 Years to 85 Years
SexALL
Healthy VolunteersNo
Study Sites26

Inclusion Criteria: * Males and females ≥ 40 years and ≤ 85 years of age at screening. * Diagnosed with HF with NYHA functional class II or III. * Screening echocardiography with LVEF ≥ 60%. * Screening NT-proBNP ≥ 300 pg/mL for participants in sinus rhythm and ≥ 900 pg/mL for participants with com...

Countries:United States
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Recent Changes (Last 90 Days)

LOWAug 27, 2026NCT06793371lastUpdatePostDate: changed
LOWAug 27, 2026NCT06793371lastUpdatePostDate: changed

Frequently asked questions about CK-4021586

What is CK-4021586 used for?

CK-4021586 is an investigational small molecule being studied for symptomatic heart failure with preserved ejection fraction (HFpEF). It is also being evaluated in healthy participants to assess its safety and tolerability. The drug is in clinical development and is not yet approved by the FDA.

What does CK-4021586 target?

CK-4021586 targets cardiac myosin, a protein involved in heart muscle contraction. By modulating cardiac myosin, the drug aims to affect heart function in conditions like heart failure with preserved ejection fraction (HFpEF). The exact mechanism of action is under investigation in clinical trials.

Who makes CK-4021586?

CK-4021586 is being developed by Cytokinetics, Incorporated, a biopharmaceutical company. The company is conducting clinical trials to evaluate the drug's safety, tolerability, and efficacy in healthy participants and in patients with symptomatic heart failure with preserved ejection fraction (HFpEF).

What phase is CK-4021586 in?

CK-4021586 is in Phase 1 and Phase 2 clinical development. A Phase 1 study in healthy participants has been completed, and a Phase 2 study in patients with symptomatic heart failure with preserved ejection fraction (HFpEF) is currently recruiting. The drug is investigational and not yet approved.

What clinical trials is CK-4021586 in?

CK-4021586 is being studied in two clinical trials. NCT05877053 is a completed Phase 1 single and multiple ascending dose study in healthy participants. NCT06793371, known as AMBER-HFpEF, is a recruiting Phase 2 study evaluating safety and tolerability in patients with symptomatic heart failure with preserved ejection fraction (HFpEF).

Is CK-4021586 the same as other names?

CK-4021586 is also known by its dose strengths: 150 mg, 300 mg, 450 mg, and 600 mg. These refer to the same drug substance being tested in clinical trials. No other alternative names have been reported.