Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Vericiguat tablet
Vericiguat · 6 trials · 6 indications
The time to first occurrence of the composite endpoint of CV death or HF hospitalization was defined as the time from randomization to the first event of CV death or HF hospitalization. Randomized participants without a HF hospitalization or CV death event at the time of analysis were censored at the last available information, when the protocol pre-specified number of total CV death events was achieved (primary completion analysis data cutoff), or the date of their non-CV death, whichever occurred first. Events were confirmed by a clinical events committee (CEC). Protocol-specified final analyses are reported here with a primary completion data cutoff. Time-to-event methodology was used to evaluate the results and the number of participants with a CV death or HF hospitalization event per 100 patient-years at risk is presented.
Time to First Occurrence of Composite Endpoint of CV Death or HF Hospitalization was analyzed using a one-sided stratified log-rank test. Randomized participants without any HF hospitalization or CV death event at the time of analysis were censored at their last available information, the date of their non-CV death, or the primary analysis database cutoff date of 18-June-2019, whichever occurred first. A clinical events committee (CEC) reviewed and adjudicated the endpoint events. A time-to-event methodology was used to evaluate the results; the incidence rate of participants with an event (number of participants with an event per 100 participant-years at risk) is provided.
The difference in absolute change in coronary cross-sectional area (in mm²) from rest to isometric handgrip exercise (IHE) in the group randomized to vericiguat from that measured at baseline, prior to the initiation of vericiguat, to that measured at the end of the study drug administration period, six weeks following initiation of the titrated dose, as assessed by MRI.
The difference in relative change in coronary cross-sectional area (in %) from rest to isometric handgrip exercise (IHE) in the group randomized to vericiguat from that measured at baseline prior to the initiation of vericiguat, to that measured at the end of the study drug administration period, six weeks following initiation of the titrated dose, as assessed by MRI.
The difference in absolute change in coronary cross-sectional area (in mm²) from rest to isometric handgrip exercise (IHE) as assessed by MRI.
The difference in percentage change in coronary cross-sectional area (%) from rest to isometric handgrip exercise (IHE) between the vericiguat and placebo groups, as assessed from the baseline MRI to the follow-up MRI, six weeks following initiation of the titrated dose.
The change from baseline to Week 16 of the Base Period in log-transformed NT-proBNP will be reported.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants with one or more AEs in the Extension Period will be reported.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinue study drug in the Extension Period due to an AE will be reported.
Regular measurements of blood pressure after a vericiguat administration on the first and on the last days of each dose step of vericiguat, and on the first days of ISMN up-titration.
Regular measurements heart rate after a vericiguat administration on the first and on the last days of each dose step of vericiguat, and on the first days of ISMN up-titration.
Area under the concentration vs. time curve from zero to infinity after single dose administration
Maximum observed drug concentration in measured matrix after single dose administration
Area under the concentration vs. time curve from zero to infinity after single dose administration
Maximum observed drug concentration in measured matrix after single dose administration
| Arm | Type | Description |
|---|---|---|
| Vericiguat | EXPERIMENTAL | Participants receive a starting dose of 2.5 mg of vericiguat taken orally once daily. The vericiguat dose will be titrated to 5 mg and to 10 mg. |
| Placebo | PLACEBO_COMPARATOR | Participants receive a starting matching placebo to vericiguat dose of 2.5 mg taken orally once daily. The matching placebo dose will be sham titrated to 5 mg and to 10 mg. |
| Base Period: Vericiguat | EXPERIMENTAL | Participants in the Base Period receive 2.5 mg or 5 mg or 10 mg vericiguat administered orally once daily in tablet form for 52 weeks; or 0.2 mg/mL or 1 mg/mL vericiguat administered orally once daily in suspension form for 52 weeks. |
| Base Period: Placebo | PLACEBO_COMPARATOR | Participants in the Base Period receive placebo for vericiguat administered orally once daily in tablet form for 52 weeks, or administered orally once daily in suspension form for 52 weeks. |
| Extension Period: Vericiguat | EXPERIMENTAL | Participants in the Extension Period receive either 2.5 mg or 5 mg or 10 mg vericiguat administered orally once daily in tablet form; or 0.2 mg/mL or 1 mg/mL vericiguat administered orally once daily in suspension form; following completion of the Base Period. |
| Vericiguat + isosorbite mononitrate | EXPERIMENTAL | Subjects received Isosorbide mononitrate (ISMN) up-titration with 30 mg / 60 mg, about 7 days each,prior to start of vericiguat administration. Then subjects received 2.5 mg vericiguat for about 14 days, followed by 5 mg vericiguat for about 14 days, followed by 10 mg vericiguat for about 14 days together 60 mg ISMN od on each day of vericiguat administration, taken 1 hour prior to vericiguat (in-house days) or together with vericiguat (out-patient days). |
| Placebo + isosorbite mononitrate | PLACEBO_COMPARATOR | Subjects received Isosorbide mononitrate (ISMN) up-titration with 30 mg / 60 mg, about 7 days each, prior to start of placebo administration. Then subjects received placebo matching 2.5 mg vericiguat for about 14 days, followed by placebo matching 5 mg vericiguat for about 14 days, followed by placebo matching 10 mg vericiguat for about 14 days together 60 mg ISMN od on each day of placebo administration, taken 1 hour prior to placebo (in-house days) or together with placebo (out-patient days). |
| Patients with normal creatine clearance (CLCR) | EXPERIMENTAL | Subjects with renal impairment according to their medical history and estimated glomerular filtration rate (eGFR) at screening but had normal creatinine clearance at the pre-profile day (-01day) |
| Normal renal function (Healthy subjects) | EXPERIMENTAL | Subjects with creatinine clearance at pre-profile day \>80 ml/min |
| Mildly impaired renal function | EXPERIMENTAL | Subjects with creatinine clearance at pre-profile day in the range of 50-80 ml/min |
| Moderately impaired renal function | EXPERIMENTAL | Subjects with creatinine clearance at pre-profile day in the range of 30-\<50 ml/min |
| Severely impaired renal function | EXPERIMENTAL | Subjects with creatinine clearance at pre-profile day \<30 ml/min |
| Name | Type | Description |
|---|---|---|
| Vericiguat | DRUG | 2.5, 5.0, or 10.0 mg orally once daily |
| Placebo | DRUG | 0 mg matching placebo for 2.5 mg, 5 mg, and 10 mg of vericiguat |
| Placebo for vericiguat | DRUG | 2.5, 5.0, or 10.0 mg orally once daily |
| Vericiguat tablet | DRUG | 2.5 mg or 5 mg or 10 mg vericiguat administered orally once daily in tablet form |
| Vericiguat suspension | DRUG | 0.2 mg/mL or 1 mg/mL vericiguat administered orally once daily in suspension form |
| Placebo tablet | DRUG | Placebo for vericiguat administered orally once daily in tablet form |
| Placebo suspension | DRUG | Placebo for vericiguat administered orally once daily in suspension form |
| Vericiguat (BAY1021189) | DRUG | 2.5 mg/tablet; 5 mg/tablet or 10 mg/tablet |
| Isosorbide mononitrate (ISMN) | DRUG | 30 mg/tablet or 60 mg/tablet |
Inclusion Criteria: * History of chronic HF \[New York Heart Association (NYHA) Class II to IV\] on guideline-directed medical therapy for heart failure (GDMT) with no HF hospitalization within 6 months or outpatient IV diuretic use within 3 months before randomization. * Left ventricular ejection ...
Vericiguat is an investigational small molecule being developed for cardiovascular conditions including heart failure, coronary artery disease, chronic heart failure with reduced ejection fraction, and metabolic syndrome. It is currently in Phase 3 clinical development and is not yet approved by the FDA.
Vericiguat is an activator that targets the soluble guanylate cyclase enzyme, specifically the GUCY1B1, GUCY1A2, and GUCY1A1 subunits. By activating this enzyme, it is designed to modulate the nitric oxide signaling pathway relevant to heart failure.
Vericiguat is being developed by Merck & Company, Inc., which trades under the ticker symbol MRK on the New York Stock Exchange. The company is conducting clinical trials to evaluate the drug's safety and efficacy in heart failure patients.
Vericiguat is in Phase 3 clinical development for chronic heart failure with reduced ejection fraction. It is an investigational drug, meaning it has not received FDA approval and is still undergoing clinical trials to assess its safety and effectiveness.
Vericiguat has been studied in several clinical trials, including NCT02861534, a completed Phase 3 study in 5,050 participants with heart failure with reduced ejection fraction, and NCT05093933, another completed Phase 3 trial with 6,106 participants. An ongoing Phase 2 trial, NCT05714085, is recruiting pediatric patients.
Yes, Vericiguat tablet is another name for Vericiguat. The drug is being developed by Merck & Company, Inc. (MRK) and is currently in Phase 3 trials for heart failure with reduced ejection fraction. It is an investigational small molecule activator of soluble guanylate cyclase.