Symptomatic Heart Failure With Preserved Ejection Fraction (HFpEF)
Conditions
Keywords
Symptomatic heart failure with preserved ejection fraction, HFpEF, Heart failure, CK-4021586, CK-586, AMBER-HFpEF, AMBER, Cardiac myosin inhibitor, CMI, CY 9021, ulacamten
Brief summary
This is a Phase 2 dose-finding study in adult participants with symptomatic HFpEF.
Interventions
DRUGCK-4021586 (150 mg, 300 mg, 450 mg, and 600 mg)
CK-4021586 administered orally
DRUGPlacebo to match CK-4021586
Placebo administered orally
Sponsors
Cytokinetics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
No
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 comorbid atrial fibrillation or flutter. * Body mass index \< 40 kg/m2. * Participants on beta-blockers, angiotensin-converting enzyme (ACE)/angiotensin II receptor blocker (ARB) or angiotensin receptor/neprilysin inhibitor (ARNI), must be on stable doses for more than 30 days prior to screening. * Participants on a glucagon-like peptide-1 (GLP-1) agonist must be on a stable dose for more than 24 weeks prior to screening with no anticipated plans to change dose during this study.
Exclusion criteria
* History or evidence of any other clinically significant disorder, malignancy, active infection, other condition, or disease that, in the opinion of the investigator or the Medical Monitor, would pose a risk to patient safety or interfere with the study evaluation, procedures, or completion. * Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in LVEF | Baseline to Week 6 and Week 12 | Change from baseline in LVEF at Week 6 and Week 12 |
| Plasma concentrations of CK-4021586 | 12 weeks | Observed 2-hour post dose plasma concentration (C2hr) and minimum plasma concentration (Cmin) for CK-4021586 over the dosing interval |
| Change in NT-proBNP | Baseline to Week 6 and Week 12 | Change from baseline values in NT-proBNP to Week 6 and Week 12 |
| Concentration-response relationship of CK-4021586 on NT-proBNP change | Baseline to Week 12 | Slope of the relationship of plasma concentration of CK-4021586 to the change from baseline in the NT-proBNP |
| Concentration-response relationship of CK-4021586 to LVEF change | Baseline to Week 12 | Slope of the relationship of plasma concentration of CK-4021586 to the change from baseline in the LVEF |
Countries
United States
Contacts
CONTACTCytokinetics MD
STUDY_DIRECTORCytokinetics MD
Cytokinetics
Outcome results
None listed