Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as CXL-1427, HNO Donor, CXL-1427 Ascending Dose, CXL-1427 Descending Dose
BMS-986231 · 9 trials · 14 indications
The total volume of urinary output 4 hours after 40 mg furosemide bolus given to participants with HFrEF while on BMS-986231 compared to placebo: absolute difference in total volume and % change from placebo. Sequence 1: Placebo in period 1, drug in period 2 Sequence 2: Drug in period 1, placebo in period 2
The objective is to evaluate the effects of BMS-986231 on the left ventricular (LV) systolic function by stroke volume index (SVI) assessed by echocardiography compared to placebo.
Percentage of participants with clinically relevant hypotension, defined by systolic blood pressure (SBP) \< 90 mm Hg (confirmed by a repeated value \< 90 mm Hg) or symptoms of hypotension, up to 6 hours after the end of study drug infusion
A treatment-emergent adverse event (TEAE) was defined as an AE with onset after the start of the study drug infusion at Hour 00:00 through 30 days after the stop of the study drug infusion. All TEAEs and pertinent subsets of TEAEs (e.g., TEAEs with onset during the infusion of study drug, serious TEAEs, etc.) were summarized by system organ class (SOC), preferred term (PT) and treatment group
The effect of CXL-1427 on PCWP is presented as the mean time-averaged change from baseline over the course of infusion of CXL-1427 or placebo in adjudicated pulmonary capillary wedge pressure (PCWP) on a modified intent-to-treat population
Pulmonary artery diastolic pressure (PAD) was measured by an indwelling PA catheter. Pulmonary artery diastolic pressure (PAD) approximates pulmonary capillary wedge pressure in normal individuals. The effects of CXL-1427 on time-averaged PAD during the course of the infusion are presented.
Cardiac index is a measure of cardiac function, relating the cardiac output from the left ventricle in one minute to body surface area. It is calculated using the Fick principle, using oxygen consumption measured with a metabolic cart, hemoglobin levels, and the difference between arterial and superior vena cava oxygen saturation measured by co-oximetry. Cardiac index as calculated by the Fick method was performed using an assumed oxygen consumption value of 125 ml/min per m2 of body surface area. i.e., an assumed Fick method.
Measured by plasma concentrations
Measured by plasma urine, feces, and vomit (if applicable) volumes and radioactivity counts
Measured by plasma concentrations
Measured by plasma concentrations
Measured by plasma concentrations
Measured by plasma concentrations
| Arm | Type | Description |
|---|---|---|
| Placebo+Diuretic to BMS-986231+Diuretic | EXPERIMENTAL | Administered in a cross over design with 8-hour continuous infusions and 7-28 day wash-out periods |
| BMS-986231+Diuretic to Placebo+Diuretic | EXPERIMENTAL | Administered in a cross over design with 8-hour continuous infusions and 7-28 day wash-out periods |
| Placebo/BMS-986231/NTG | EXPERIMENTAL | administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods |
| Placebo/NTG/BMS-986231 | EXPERIMENTAL | administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods |
| NTG/Placebo/BMS-986231 | EXPERIMENTAL | administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods |
| NTG/BMS-986231/Placebo | EXPERIMENTAL | administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods |
| BMS-986231/Placebo/NTG | EXPERIMENTAL | administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods |
| BMS-986231/NTG/Placebo | EXPERIMENTAL | administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods |
| Part 1 Cohort 1 HNO Donor | EXPERIMENTAL | - |
| Placebo Part 1 Cohort 1 | PLACEBO_COMPARATOR | - |
| Part 2 Cohort 2 HNO Donor- low dose | EXPERIMENTAL | - |
| Part 2 Cohort 2 HNO Donor- high dose | EXPERIMENTAL | - |
| Placebo Part 2 Cohort 2 | PLACEBO_COMPARATOR | - |
| CXL-1427 Starting Dose | EXPERIMENTAL | The Starting dose of CXL-1427 in the dose escalation arms will be 3mcg/kg/min |
| CXL-1427 Dose Level 2 | EXPERIMENTAL | The Second Dose level of CXL-1427 will be evaluated in the Dose Escalation Arm of the study as determined by the independent dose escalation committee |
| CXL-1427 Dose Level 3 | EXPERIMENTAL | The Third Dose level of CXL-1427 will be evaluated in the Dose Escalation Arm of the study as determined by the independent dose escalation committee |
| CXL-1427 Dos Level 3 | EXPERIMENTAL | The Third Dose level of CXL-1427 will be evaluated in the Dose Escalation Arm of the study as determined by the independent dose escalation committee |
| CXL-1427 Dose Level 4 | EXPERIMENTAL | The forth level of CXL-1427 will be evaluated in the Dose Escalation Arm of the study as determined by the independent dose escalation committee |
| Expansion Cohort 1 | EXPERIMENTAL | Up to 16 Patients will be enrolled across 1 or more of the previously evaluated Dose escalation Levels as determined by the independent dose escalation committee |
| Placebo for Dose Escalation and Expansion Cohort | PLACEBO_COMPARATOR | Each Dose escalation Arm of the study will have a placebo group in a 2:1 ratio to active treatment for the first 3 patients enrolled and 4:1 to active treatment in the remaining 5 patients so that the overall randomization ratio in each Dose escalation arm will be 3:1 active to placebo. In the expansion Cohort of the study, the ratio of patients randomized to receive a 6-hour infusion of active CXL-1427 or placebo will be 3:1 |
| Mild hepatic impairment | EXPERIMENTAL | Based on Hepatic Function Impairment - Child-Pugh A score 5 to 6 points |
| Moderate hepatic impairment | EXPERIMENTAL | Based on Hepatic Function Impairment - Child-Pugh B score 7 to 9 points |
| Severe hepatic impairment | EXPERIMENTAL | Based on Hepatic Function Impairment - Child-Pugh C score 10 to 15 points |
| Normal hepatic function | EXPERIMENTAL | Based on Hepatic Function Impairment as defined by the investigator |
| Mild Renal Impairment | EXPERIMENTAL | Mild renal impairment defined as eGFR 60 to \<90 mL/min/1.73 m\^2 |
| Moderate renal impairment | EXPERIMENTAL | Moderate renal impairment defined as eGFR 30 to \<60 mL/min/1.73 m\^2 |
| Severe renal impairment | EXPERIMENTAL | Severe renal impairment defined as eGFR \<30 mL/min/1.73 m\^2, not requiring dialysis |
| Normal renal function | EXPERIMENTAL | Normal renal function defined as eGFR ≥90 mL/min/1.73 m\^2 |
| BMS-986231 Intravenous Infusion | EXPERIMENTAL | A single continuous intravenous infusion of BMS-986231 |
| Panel 1 Arm | EXPERIMENTAL | BMS-986231 and BMS-986231 Placebo intravenously |
| Panel 2 Arm | EXPERIMENTAL | BMS-986231 and BMS-986231 Placebo intravenously |
| Panel 3 Arm | EXPERIMENTAL | BMS-986231 and BMS-986231 Placebo intravenously |
| CXL-1427 (BMS-986231) | EXPERIMENTAL | Experimental |
| Placebo | PLACEBO_COMPARATOR | Placebo |
| Name | Type | Description |
|---|---|---|
| BMS-986231 | DRUG | Intravenous administration |
| Furosemide | DRUG | Intravenous administration |
| Placebo | DRUG | Intravenous administration |
| HNO Donor | DRUG | Infusion |
| Nitroglycerin (NTG) | DRUG | Infusion |
| CXL-1427 | DRUG | - |
| BMS-986231 Placebo | DRUG | - |
| CXL-1427 Ascending Dose | DRUG | - |
| CXL-1427 Descending Dose | DRUG | - |
For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Left ventricular ejection fraction \<45%, as assessed by echocardiography, a multigated acquisition (MUGA) scan or magnetic resonance imaging (MRI) scan with...
BMS-986231 is an investigational small molecule being developed for cardiovascular conditions including myocardial failure, liver dysfunction, acute heart decompensation, and cardiac failure. It is currently in Phase 2 clinical development and has not been approved by the FDA.
BMS-986231 is being developed by Bristol-Myers Squibb Company, traded on the New York Stock Exchange under the ticker BMY. The company is conducting clinical trials to evaluate the drug's safety and efficacy in patients with heart failure and related conditions.
BMS-986231 is in Phase 2 clinical development. The drug is investigational and has not received regulatory approval. Clinical trials have been completed, including a Phase 2 study in patients with heart failure and reduced heart function.
BMS-986231 has completed several clinical trials, including NCT02932969 and NCT03210909 in healthy volunteers, NCT03332186 in patients with varying kidney function, and NCT03730961, a Phase 2 study in heart failure patients receiving loop diuretics.
No alternative names for BMS-986231 have been disclosed. The drug is identified solely by its development code BMS-986231 in clinical trial registrations and scientific literature.