Acute Decompensated Heart Failure
Conditions
Keywords
Heart failure
Brief summary
The purpose of the study is to assess the safety of BMS-986259 in stable participants hospitalized for acute decompensated heart failure.
Interventions
DRUGBMS-986259
Specified dose on specified days
OTHERPlacebo
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Participants currently hospitalized for acute decompensated heart failure (ADHF) * Participants must be hemodynamically stable, as assessed by the investigator * Men must agree to follow specific methods of contraception, if applicable, while participating in the trial * Women participants must have documented proof that they are not of childbearing potential
Exclusion criteria
* Acute cardiovascular condition other than heart failure (HF) decompensation * Cardiogenic shock at presentation to emergency room (ER) or at any time before randomization * Recipient of ventricular assist devices or use of any cardiac extracorporeal devices, within 12 weeks of study randomization * Participants with contraindications to vasodilator therapy such as restrictive or obstructive cardiomyopathy, severe mitral or aortic stenosis Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Experiencing Clinically Relevant Hypotension | From first dose to 30 days following first dose | Clinically Relevant Hypotension is defined as occurrence of any of the following: * Supine Systolic Blood Pressure (SBP) \<85 mmHg (confirmed by repeat measurement within 30 minutes), regardless of symptoms of hypotension * Supine SBP \<90 mmHg (confirmed by repeat measurement within 30 minutes) AND symptoms of hypotension (eg, dizziness, lightheadedness, etc). |
Secondary
| Measure | Time frame |
|---|---|
| Maximum Observed Serum Concentration (Cmax) | Day 1 and Day 5 of study treatment |
| Time of Maximum Observed Serum Concentration (Tmax) | Day 1 and Day 5 of study treatment |
| Area Under the Concentration-Time Curve Within a Dosing Interval (AUC(TAU)) | Day 1 and Day 5 of study treatment |
| Trough Concentration (Ctrough) | Day 2 through Day 14 of study treatment (with the exception of Day 11, for which data is not available) |
Countries
Argentina, Czechia, Greece, Israel, Poland, United Kingdom
Participant flow
Pre-assignment details
25 participants were randomized and treated.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo matching BMS-986259 | 13 |
| BMS-986259 3 mg BMS-986259 administered subcutaneously QD for 14 days | 12 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 |
| Overall Study | Other reasons | 0 | 1 |
| Overall Study | Participant withdrew consent | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | BMS-986259 3 mg | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 6 Participants | 15 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 6 Participants | 10 Participants |
| Age, Continuous | 65.1 Years STANDARD_DEVIATION 12.18 | 63.1 Years STANDARD_DEVIATION 15.65 | 64.1 Years STANDARD_DEVIATION 13.69 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 12 Participants | 25 Participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 9 Participants | 9 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 13 | 0 / 12 |
| other Total, other adverse events | 3 / 13 | 8 / 12 |
| serious Total, serious adverse events | 5 / 13 | 2 / 12 |
Outcome results
Primary
Percentage of Participants Experiencing Clinically Relevant Hypotension
Clinically Relevant Hypotension is defined as occurrence of any of the following: * Supine Systolic Blood Pressure (SBP) \<85 mmHg (confirmed by repeat measurement within 30 minutes), regardless of symptoms of hypotension * Supine SBP \<90 mmHg (confirmed by repeat measurement within 30 minutes) AND symptoms of hypotension (eg, dizziness, lightheadedness, etc).
Time frame: From first dose to 30 days following first dose
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Experiencing Clinically Relevant Hypotension | 15.4 Percent of participants |
| BMS-986259 3 mg | Percentage of Participants Experiencing Clinically Relevant Hypotension | 16.7 Percent of participants |
Secondary
Area Under the Concentration-Time Curve Within a Dosing Interval (AUC(TAU))
Time frame: Day 1 and Day 5 of study treatment
Population: All participants receiving study drug with available measurements
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Area Under the Concentration-Time Curve Within a Dosing Interval (AUC(TAU)) | Day 1 | 1778 h*ng/mL | Geometric Coefficient of Variation 40 |
| Placebo | Area Under the Concentration-Time Curve Within a Dosing Interval (AUC(TAU)) | Day 5 | 5156 h*ng/mL | Geometric Coefficient of Variation 36 |
Secondary
Maximum Observed Serum Concentration (Cmax)
Time frame: Day 1 and Day 5 of study treatment
Population: All participants receiving study drug with available measurements
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Maximum Observed Serum Concentration (Cmax) | Day 1 | 105 ng/mL | Geometric Coefficient of Variation 49 |
| Placebo | Maximum Observed Serum Concentration (Cmax) | Day 5 | 268 ng/mL | Geometric Coefficient of Variation 31 |
Secondary
Time of Maximum Observed Serum Concentration (Tmax)
Time frame: Day 1 and Day 5 of study treatment
Population: All participants receiving study drug with available measurements
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Time of Maximum Observed Serum Concentration (Tmax) | Day 1 | 11.0 Hours |
| Placebo | Time of Maximum Observed Serum Concentration (Tmax) | Day 5 | 7.97 Hours |
Secondary
Trough Concentration (Ctrough)
Time frame: Day 2 through Day 14 of study treatment (with the exception of Day 11, for which data is not available)
Population: All participants receiving study drug with available measurements
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Trough Concentration (Ctrough) | Day 2 | 79.9 ng/mL | Geometric Coefficient of Variation 36 |
| Placebo | Trough Concentration (Ctrough) | Day 3 | 145 ng/mL | Geometric Coefficient of Variation 32.3 |
| Placebo | Trough Concentration (Ctrough) | Day 4 | 181 ng/mL | Geometric Coefficient of Variation 28.9 |
| Placebo | Trough Concentration (Ctrough) | Day 5 | 185 ng/mL | Geometric Coefficient of Variation 32.4 |
| Placebo | Trough Concentration (Ctrough) | Day 6 | 210 ng/mL | Geometric Coefficient of Variation 27.3 |
| Placebo | Trough Concentration (Ctrough) | Day 7 | 260 ng/mL | Geometric Coefficient of Variation 41.3 |
| Placebo | Trough Concentration (Ctrough) | Day 8 | 226 ng/mL | Geometric Coefficient of Variation 69.4 |
| Placebo | Trough Concentration (Ctrough) | Day 9 | 252 ng/mL | Geometric Coefficient of Variation 48.1 |
| Placebo | Trough Concentration (Ctrough) | Day 10 | 259 ng/mL | Geometric Coefficient of Variation 49.7 |
| Placebo | Trough Concentration (Ctrough) | Day 12 | 229 ng/mL | Geometric Coefficient of Variation 22.9 |
| Placebo | Trough Concentration (Ctrough) | Day 13 | 248 ng/mL | Geometric Coefficient of Variation 50.5 |
| Placebo | Trough Concentration (Ctrough) | Day 14 | 246 ng/mL | Geometric Coefficient of Variation 7.53 |