Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT06736574 | Study With Omecamtiv Mecarbil (CK-1827452) to Treat Chronic Heart Failure With Severely Reduced Ejection Fraction | PHASE3 | RECRUITING | 1,800 | — | — | Dec 19, 2024 | Dec 1, 2027 | May 5, 2026 | 185 | United States, Canada +7 |
| NCT02929329 | Registrational Study With Omecamtiv Mecarbil (AMG 423) to Treat Chronic Heart Failure With Reduced Ejection Fraction | PHASE3 | COMPLETED | 8,256 | — | — | Jan 6, 2017 | Sep 14, 2020 | Nov 5, 2021 | 1033 | United States, Argentina +34 |
| NCT01300013 | Study to Evaluate the Safety and Efficacy of IV Infusion Treatment With Omecamtiv Mecarbil in Subjects With Left Ventricular Systolic Dysfunction Hospitalized for Acute Heart Failure (ATOMIC-AHF) | PHASE2 | COMPLETED | 614 | — | — | Apr 1, 2011 | Sep 1, 2013 | Jul 27, 2021 | 150 | United States, Australia +17 |
| NCT01380223 | A Pharmacokinetic and Pharmacodynamic Study of Omecamtiv Mecarbil in Healthy Volunteers | PHASE1 | COMPLETED | 35 | — | — | Aug 1, 2005 | Apr 1, 2006 | Oct 14, 2015 | 1 | United Kingdom |
Efficacy of omecamtiv mecarbil compared with placebo on the risk of HF outcomes in patients with symptomatic HFrEF and severely reduced ejection fraction in the setting of guideline-directed medical therapy per local standard of care.
The primary outcome was a composite of a heart-failure (HF) event or cardiovascular (CV) death, whichever occurred first, in a time-to-event analysis. A heart-failure event was defined as an urgent clinic visit, emergency department visit, or hospitalization for subjectively and objectively worsening heart failure leading to treatment intensification beyond a change in oral diuretic therapy. All deaths and HF events were adjudicated by an independent external clinical events committee (CEC) at the Duke Clinical Research Institute, using standardized definitions based on the recent American College of Cardiology/American Heart Association (ACC/AHA) standards for endpoint definitions in cardiovascular clinical trials. Time to cardiovascular death or first HF event was analyzed using Kaplan-Meier (KM) methods. Since the median was not calculated, the percentage of participants with a positively adjudicated event during the study is reported.
The highest infusion rate tolerated by at least eight subjects. A dose was intolerable if: 1) the pattern of intolerance clearly distinguished active drug from placebo, or 2) the number of subjects intolerant of the dose level in question was at least 3 more than the number of subjects intolerant of placebo.
| Arm | Type | Description |
|---|---|---|
| Omecamtiv Mecarbil | EXPERIMENTAL | Participants randomized to omecamtiv mecarbil will be dosed based on their omecamtiv mecarbil plasma concentration at 25, 37.5 or 50 mg twice daily until at least 850 participants experience a HF event or CV death, whichever comes first. |
| Placebo | PLACEBO_COMPARATOR | Participants randomized to placebo will receive placebo twice daily until at least 850 participants experience a HF event or CV death, whichever comes first. |
| Dose-escalation Cohort 1 | EXPERIMENTAL | 4 treatment periods consisting of a 2 hour placebo infusion (single blind) followed by a 6 hour infusion of study drug or placebo. Each subject will receive 3 active ascending doses of study drug and 1 dose of placebo randomized into the sequence of escalating doses in a double-blind manner. Treatment periods occur at least 7 days apart. |
| Dose-escalation Cohort 2 | EXPERIMENTAL | 4 treatment periods consisting of a 2 hour placebo infusion (single blind) followed by a 6 hour infusion of study drug or placebo. Each subject will receive 3 active ascending doses of study drug and 1 dose of placebo randomized into the sequence of escalating doses in a double-blind manner. Treatment periods occur at least 7 days apart. |
| Dose-escalation Cohort 3 | EXPERIMENTAL | 4 treatment periods consisting of a 2 hour placebo infusion (single blind) followed by a 6 hour infusion of study drug or placebo. Each subject will receive 3 active ascending doses of study drug and 1 dose of placebo randomized into the sequence of escalating doses in a double-blind manner. Treatment periods occur at least 7 days apart. |
| Dose-escalation Cohort 4 | EXPERIMENTAL | 4 treatment periods consisting of a 2 hour placebo infusion (single blind) followed by a 6 hour infusion of study drug or placebo. Each subject will receive 3 active ascending doses of study drug and 1 dose of placebo randomized into the sequence of escalating doses in a double-blind manner. Treatment periods occur at least 7 days apart. |
| Name | Type | Description |
|---|---|---|
| Omecamtiv Mecarbil (OM) | DRUG | Oral Tablet |
| Placebo | DRUG | Oral Tablet |
| Omecamtiv Mecarbil | DRUG | Omecamtiv mecarbil tablets for oral administration |
| Standard of Care | DRUG | Participants were required to be optimally managed with standard of care therapies for chronic HF (eg, beta blockers, renin angiotensin aldosterone system inhibitors), consistent with regional clinical practice guidelines, unless contraindicated. |
Inclusion Criteria: Adult patients who meet all the following criteria at screening may be included in the study: * Are between ≥ 18 years and ≤ 85 years at the signing of informed consent * Have a history of chronic HFrEF, defined as requiring treatment for HF for a minimum of 3 months prior to s...