Heart Failure
Conditions
Keywords
Heart Failure, Cardiac Failure
Brief summary
The purpose of this study is to investigate the safety, tolerability, pharmacodynamics (how the study medication affects the body) and pharmacokinetics (how the drug is absorbed in the body, how it is distributed within the body and removed from the body over time) of an intravenous administration of JNJ-39588146 or placebo over a 3-hour period in patients with heart failure. The highest tolerated dose received during the first 3 hours of the study will be administered to some patients for an additional 18 hours. There will be up to 3 doses given throughout the administration period over a total of up to 21 hours.
Detailed description
This study will assess the safety, tolerability, pharmacodynamics and pharmacokinetics of JNJ-39588146 or placebo (which looks like the drug being studied but has no active ingredients) in patients with heart failure. This study is being conducted in two parts. Part 1 is a randomized (study drug will be assigned by chance), double-blind (neither the physician nor patient knows the identity of the assigned drug) study of 3 intravenous doses of JNJ-39588146 or placebo administered in 1-hr intervals (for a total of 3 hours) in 60 patients with heart failure. Part 2 is an extended infusion of JNJ-39588146 and placebo that will administer the highest tolerated dose from Part 1 for an additional 18 hours. The entire duration of the infusion could be as long as 21 hours. There is a 1 in 4 chance of getting placebo. The participation period is a maximum of 42 days, including a screening visit, a 2-day in-clinic period and two follow-up visits. For both parts of the study, patients will have a cardiac catheter in place to monitor heart function. Safety evaluations, which will include ECG (electrocardiograph, measuring the electrical currents in the heart), vital signs and monitoring of side-effects will be performed. Additionally, blood and urine samples will be collected for evaluation. Part 1: Patients will receive an intravenous (IV) solution of three different doses of JNJ-39588146 or placebo administered over 1 hour periods for a total of 3 hours. Part 2: Patients participating in the sub study will continue receiving an IV solution for 18 more hours for a total of up to 21 hours of administration.
Interventions
DRUGJNJ-39588146 5 ng/kg/min
1-hour infusion of JNJ-39588146 5 ng/kg/min on Day 1
DRUGJNJ-39588146 15 ng/kg/min
1-hour infusion of JNJ-39588146 15 ng/kg/min on Day 1
DRUGJNJ-39588146 30 ng/kg/min
1-hour infusion of JNJ-39588146 30 ng/kg/min on Day 1
DRUGPlacebo
1-hour infusion of matching placebo on Day 1
DRUGJNJ-39588146 5, 15, or 30 ng/kg/min
18-hour infusion of JNJ-39588146 or matching placebo on Day 1 immediately folllowing the 3-hour infusion at a dose equal to the maximum dose tolerated by that patient during the 3-hour infusion in Part 1 of the study.
Sponsors
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
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 86 Years
Healthy volunteers
No
Inclusion criteria
* Patients must have been diagnosed with heart failure * Women must be either postmenopausal or have been surgically sterilized at least 6 months ago * Males must be willing to use an acceptable birth control method for 3 months after the last dose of study medication.
Exclusion criteria
* Patients must not have had an heart-assist device or heart transplant or be in imminent need of one * Patients must not have had an ischemic attack within the last 6 months or a heart attack within the last month * Patients must not have lung disease or congenital heart failure.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Cardiac Index (CI) | Baseline up through 3 hours post infusion initiation | The effect of JNJ-39588146 on cardiac index (CI), a hemodynamic parameter that relates heart performance to the size of the individual measured in liters per minute per square metre (l/min/m2) was evaluated in patients with heart failure (HF). The primary analysis of this study focused on the differences between the treatment groups in terms of Least Squares (LS) mean change from Baseline at each time point; thus, the results provided below consist of the JNJ-39588146 minus placebo differences in LS means (and associated confidence intervals) for change from Baseline in CI at each time point as well as treatment group LS means and Standard Errors. |
| Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Pulmonary Capillary Wedge Pressure (PCWP) | Baseline up through 3 hours post infusion initiation | The effect of JNJ-39588146 on pulmonary capillary wedge pressure (PCWP) was evaluated by administering multiple ascending doses of JNJ-39588146 or placebo over a 3-hour intravenous (IV) infusion period to patients with heart failure. The primary analysis of this study focused on the differences between the treatment groups in terms of Least Squares (LS) mean change from Baseline at each time point; thus, the results provided below consist of the JNJ-39588146 minus placebo differences in LS means (and associated confidence intervals) for change from baseline in PCWP at each time point as well as treatment group LS means and Standard Errors. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Diastolic Blood Pressure (DBP) | Baseline up through 3 hours post infusion initiation | The primary analysis of this study focused on the differences between the treatment groups in terms of LS mean change from Baseline at each time point; thus, the results provided below consist of the JNJ-39588146 minus placebo differences in Least Square (LS) means (and associated confidence intervals) for change from Baseline in diastolic blood pressure(DBP) at each time point as well as treatment group LS means and Standard Errors. |
| Post-baseline Changes Compared to Placebo (at 3-hours Post Infusion Initiation [ie, at the End of the 30 ng/kg/Min Infusion]) in Left Ventricular End Systolic Volume (LVESV) | Baseline up through 3 hours post infusion initiation | The primary analysis of this study focused on the differences between the treatment groups in terms of Least Squares (LS) mean change from Baseline at each time point; thus, the results provided below consist of the JNJ-39588146 minus placebo differences in LS means (and associated confidence intervals) for change from Baseline in left ventricular end systolic volume (LVESV) at the end of the 30 ng/kg/min infusion as well as treatment group LS means and Standard Errors. |
| Post-baseline Changes Compared to Placebo (at 3-hours Post Infusion Initiation [ie, at the End of 30 ng/kg/Min Infusion]) in Left Ventricular End Diastolic Volume (LVEDV) | Baseline up through 3 hours post infusion initiation | The primary analysis of this study focused on the differences between the treatment groups in terms of Least Squares (LS) mean change from Baseline at each time point; thus, the results provided below consist of the JNJ-39588146 minus placebo differences in LS means (and associated confidence intervals) for change from Baseline in Left Ventricular End Diastolic Volume (LVEDV) at the end of the 30 ng/kg/min infusion as well as treatment group LS means and Standard Errors. |
| Post-baseline Changes Compared to Placebo (at 3-hours Post Infusion Initiation [ie, at the End of the 30 ng/kg/Min Infusion]) in Left Ventricular Ejection Fraction (LVEF) | Baseline up through 3 hours post infusion initiation | The primary analysis of this study focused on the differences between the treatment groups in terms of Least Squares (LS) mean change from Baseline at each time point; thus, the results provided below consist of the JNJ-39588146 minus placebo differences in LS means (and associated confidence intervals) for change from Baseline in Left Ventricular Ejection Fraction (LVEF) at the end of the 30 ng/kg/min infusion as well as treatment group LS means and Standard Errors. |
| Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Heart Rate (HR) | At 1-hour, 2 hours and 3 hours post infusion initiation | The primary analysis of this study focused on the differences between the treatment groups in terms of Least Squares (LS) mean change from Baseline at each time point; thus, the results provided below consist of the JNJ-39588146 minus placebo differences in LS means (and associated confidence intervals) for change from Baseline in heart rate (HR) at each time point as well as treatment group LS means and Standard Errors. |
| Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Stroke Volume (SV) | Baseline up through 3 hours post infusion initiation | The primary analysis of this study focused on the differences between the treatment groups in terms of Least Squares (LS) mean change from Baseline at each time point; thus, the results provided below consist of the JNJ-39588146 minus placebo differences in LS means (and associated confidence intervals) for change from Baseline in Stroke Volume (SV) at the end of the 30 ng/kg/min infusion as well as treatment group LS means and Standard Errors. |
| Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Pulmonary Arterial Systolic Pressure (PASP) | Baseline up through 3 hours post infusion initiation | The primary analysis of this study focused on the differences between the treatment groups in terms of Least Squares (LS) mean change from Baseline at each time point; thus, the results provided below consist of the JNJ-39588146 minus placebo differences in LS means (and associated confidence intervals) for change from Baseline in Pulmonary Arterial Systolic Pressure (PASP) at the end of 5, 15 and 30 ng/kg/min Infusions as well as treatment group LS means and Standard Errors. |
| Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Pulmonary Arterial Diastolic Pressure (PADP) | Baseline up through 3 hours post infusion initiation | The primary analysis of this study focused on the differences between the treatment groups in terms of Least Square (LS) mean change from Baseline at each time point; thus, the results provided below consist of the JNJ-39588146 minus placebo differences in LS means (and associated confidence intervals) for change from Baseline in Pulmonary Arterial Diastolic Pressure (PADP) at the end of 5, 15 and 30 ng/kg/min Infusions as well as treatment group LS means and Standard Errors. |
| Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Calculated Systemic Vascular Resistance (SVR) | Baseline up through 3 hours post infusion initiation | The primary analysis of this study focused on the differences between the treatment groups in terms of Least Squares (LS) mean change from Baseline at each time point; thus, the results provided below consist of the JNJ-39588146 minus placebo differences in LS means (and associated confidence intervals) for change from Baseline in Calculated Systemic Vascular Resistance (SVR) at the end of 5, 15 and 30 ng/kg/min Infusions as well as treatment group LS means and Standard Errors. |
| Post-baseline Changes Compared to Placebo (at 3-hours Post Infusion Initiation [ie, at the End of the 30 ng/kg/Min Infusion]) in Fractional Shortening (FS) | Baseline up through 3 hours post infusion initiation | The primary analysis of this study focused on the differences between the treatment groups in terms of Least Squares (LS) mean change from Baseline at each time point; thus, the results provided below consist of the JNJ-39588146 minus placebo differences in LS means (and associated confidence intervals) for change from Baseline in Fractional Shortening (FS) at the end of the 30 ng/kg/min infusion as well as treatment group LS means and Standard Errors. |
| Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Systolic Blood Pressure (SBP) | Baseline up through 3 hours post infusion initiation | The primary analysis of this study focused on the differences between the treatment groups in terms of Least Squares (LS) mean change from Baseline at each time point; thus, the results provided below consist of the JNJ-39588146 minus placebo differences in LS means (and associated confidence intervals) for change from Baseline in systolic blood pressure (SBP) at each time point as well as treatment group LS means and Standard Errors. |
Countries
Belgium, Germany, Poland, Romania
Participant flow
Recruitment details
This study was conducted in 5 countries: Belgium (3 sites), Germany (3 sites), Italy (5 sites), Poland (3 sites), and Romania (3 sites). A total of 62 subjects (16 subjects in the placebo group and 46 subjects in the JNJ-39588146 group) were randomized and treated with the study drug.
Pre-assignment details
Patients had an option to participate in an 18 hour extended infusion sub-study following the initial 3-hour infusion main study with the highest dose. A total of 10 patients (7 patients in the JNJ-39588146 group and 3 patients in the placebo group) participated in the sub-study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Patients received 3 consecutive escalating intravenous (IV) infusions of placebo identical in appearance to JNJ-39588146. Each dose was planned to be infused over 1 hour for a total planned infusion time in the main study of 3 hours. Patients had an option to participate in an 18-hour extended infusion sub-study following the initial 3-hour infusion main study with the highest dose. | 16 |
| JNJ-39588146 Patients received 3 consecutive escalating intravenous (IV) infusions of JNJ-39588146. Each dose was planned to be infused over 1 hour for a total planned infusion time in the main study of 3 hours. Patients had an option to participate in an 18-hour extended infusion sub-study following the initial 3-hour infusion main study with the highest dose. | 46 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| MAIN INFUSION | Adverse Event | 1 | 0 |
| MAIN INFUSION | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Total | JNJ-39588146 | Placebo |
|---|---|---|---|
| AgeCategorical <=10 years | 0 participants | 0 participants | 0 participants |
| AgeCategorical 11 - 20 years | 0 participants | 0 participants | 0 participants |
| AgeCategorical 21 - 50 years | 16 participants | 12 participants | 4 participants |
| AgeCategorical 50 - 64 years | 30 participants | 23 participants | 7 participants |
| AgeCategorical >=65 years | 16 participants | 11 participants | 5 participants |
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 16 Participants | 11 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 46 Participants | 35 Participants | 11 Participants |
| Age Continuous | 56.8 years STANDARD_DEVIATION 12.25 | 56.6 years STANDARD_DEVIATION 12.91 | 57.6 years STANDARD_DEVIATION 10.46 |
| Region of Enrollment Belgium | 4 participants | 4 participants | 0 participants |
| Region of Enrollment Germany | 7 participants | 2 participants | 5 participants |
| Region of Enrollment Italy | 9 participants | 7 participants | 2 participants |
| Region of Enrollment Poland | 25 participants | 21 participants | 4 participants |
| Region of Enrollment Romania | 17 participants | 12 participants | 5 participants |
| Sex: Female, Male Female | 6 Participants | 5 Participants | 1 Participants |
| Sex: Female, Male Male | 56 Participants | 41 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 16 | 11 / 46 |
| serious Total, serious adverse events | 3 / 16 | 5 / 46 |
Outcome results
Primary
Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Cardiac Index (CI)
The effect of JNJ-39588146 on cardiac index (CI), a hemodynamic parameter that relates heart performance to the size of the individual measured in liters per minute per square metre (l/min/m2) was evaluated in patients with heart failure (HF). The primary analysis of this study focused on the differences between the treatment groups in terms of Least Squares (LS) mean change from Baseline at each time point; thus, the results provided below consist of the JNJ-39588146 minus placebo differences in LS means (and associated confidence intervals) for change from Baseline in CI at each time point as well as treatment group LS means and Standard Errors.
Time frame: Baseline up through 3 hours post infusion initiation
Population: The modified intent-to-treat (MITT) population included all randomized patients who received at least 1 dose of study drug, had baseline measurement and at least 1 post-baseline measurement value of at least 1 of the primary endpoints. The efficacy analysis was to be performed using the MITT analysis set.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Cardiac Index (CI) | 1 hour infusion (5 ng/kg/min) | -0.03 L/min/m2 | Standard Error 0.19 |
| Placebo | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Cardiac Index (CI) | 2 hour infusion (15 ng/kg/min) | -0.15 L/min/m2 | Standard Error 0.17 |
| Placebo | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Cardiac Index (CI) | 3 hour infusion (30 ng/kg/min) | -0.05 L/min/m2 | Standard Error 0.23 |
| JNJ-39588146 | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Cardiac Index (CI) | 1 hour infusion (5 ng/kg/min) | 0.24 L/min/m2 | Standard Error 0.14 |
| JNJ-39588146 | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Cardiac Index (CI) | 2 hour infusion (15 ng/kg/min) | 0.18 L/min/m2 | Standard Error 0.13 |
| JNJ-39588146 | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Cardiac Index (CI) | 3 hour infusion (30 ng/kg/min) | 0.52 L/min/m2 | Standard Error 0.17 |
Comparison: 90% confidence intervals and p values represent the placebo-subtracted LS mean change from baseline in cardiac index (CI) at the end of the 5 ng/kg/min dose.p-value: 0.059590% CI: [-0.016, 0.564]ANCOVA
Comparison: 90% confidence intervals and p values represent the placebo-subtracted LS mean change from baseline in cardiac index (CI) at the end of the 15 ng/kg/min dose.p-value: 0.021590% CI: [0.064, 0.595]ANCOVA
Comparison: 90% confidence intervals and p values represent the placebo-subtracted LS mean change from baseline in cardiac index (CI) at the end of the 30 ng/kg/min dose.p-value: 0.004990% CI: [0.214, 0.921]ANCOVA
Primary
Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Pulmonary Capillary Wedge Pressure (PCWP)
The effect of JNJ-39588146 on pulmonary capillary wedge pressure (PCWP) was evaluated by administering multiple ascending doses of JNJ-39588146 or placebo over a 3-hour intravenous (IV) infusion period to patients with heart failure. The primary analysis of this study focused on the differences between the treatment groups in terms of Least Squares (LS) mean change from Baseline at each time point; thus, the results provided below consist of the JNJ-39588146 minus placebo differences in LS means (and associated confidence intervals) for change from baseline in PCWP at each time point as well as treatment group LS means and Standard Errors.
Time frame: Baseline up through 3 hours post infusion initiation
Population: The modified intent-to-treat (MITT) population included all randomized patients who received at least 1 dose of study drug, had baseline measurement and at least 1 post-baseline measurement value of at least 1 of the primary endpoints. The efficacy analysis was to be performed using the MITT analysis set.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Pulmonary Capillary Wedge Pressure (PCWP) | 1 hour infusion (5 ng/kg/min) | -0.75 mmHg | Standard Error 1.43 |
| Placebo | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Pulmonary Capillary Wedge Pressure (PCWP) | 2 hour infusion (15 ng/kg/min) | 0.15 mmHg | Standard Error 1.81 |
| Placebo | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Pulmonary Capillary Wedge Pressure (PCWP) | 3 hour infusion (30 ng/kg/min) | 0.05 mmHg | Standard Error 1.97 |
| JNJ-39588146 | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Pulmonary Capillary Wedge Pressure (PCWP) | 1 hour infusion (5 ng/kg/min) | -0.84 mmHg | Standard Error 1.03 |
| JNJ-39588146 | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Pulmonary Capillary Wedge Pressure (PCWP) | 2 hour infusion (15 ng/kg/min) | -1.20 mmHg | Standard Error 1.31 |
| JNJ-39588146 | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Pulmonary Capillary Wedge Pressure (PCWP) | 3 hour infusion (30 ng/kg/min) | -2.53 mmHg | Standard Error 1.42 |
Comparison: 90% confidence intervals and p values represent the placebo-subtracted LS mean change from baseline in pulmonary capillary wedge pressure (PCWP) at the end of the 5 ng/kg/min dose.p-value: 0.472990% CI: [-2.312, 2.131]ANCOVA
Comparison: 90% confidence intervals and p values represent the placebo-subtracted LS mean change from baseline in pulmonary capillary wedge pressure (PCWP) at the end of the 15 ng/kg/min dose.p-value: 0.212390% CI: [-4.164, 1.464]ANCOVA
Comparison: 90% confidence intervals and p values represent the placebo-subtracted LS mean change from baseline in pulmonary capillary wedge pressure (PCWP) at the end of the 30 ng/kg/min dose.p-value: 0.082190% CI: [-5.639, 0.483]ANCOVA
Secondary
Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Calculated Systemic Vascular Resistance (SVR)
The primary analysis of this study focused on the differences between the treatment groups in terms of Least Squares (LS) mean change from Baseline at each time point; thus, the results provided below consist of the JNJ-39588146 minus placebo differences in LS means (and associated confidence intervals) for change from Baseline in Calculated Systemic Vascular Resistance (SVR) at the end of 5, 15 and 30 ng/kg/min Infusions as well as treatment group LS means and Standard Errors.
Time frame: Baseline up through 3 hours post infusion initiation
Population: The modified intent-to-treat (MITT) population included all randomized patients who received at least 1 dose of study drug, had baseline measurement and at least 1 post-baseline measurement value of at least 1 of the primary endpoints. The efficacy analysis was to be performed using the MITT analysis set.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Calculated Systemic Vascular Resistance (SVR) | 1 hour infusion (5 ng/kg/min) | 67.41 dyn.s.cm-5 | Standard Error 147.97 |
| Placebo | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Calculated Systemic Vascular Resistance (SVR) | 2 hour infusion (15 ng/kg/min) | 321.97 dyn.s.cm-5 | Standard Error 116.73 |
| Placebo | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Calculated Systemic Vascular Resistance (SVR) | 3 hour infusion (30 ng/kg/min) | 281.79 dyn.s.cm-5 | Standard Error 131.69 |
| JNJ-39588146 | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Calculated Systemic Vascular Resistance (SVR) | 1 hour infusion (5 ng/kg/min) | -196.95 dyn.s.cm-5 | Standard Error 105.33 |
| JNJ-39588146 | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Calculated Systemic Vascular Resistance (SVR) | 2 hour infusion (15 ng/kg/min) | -61.36 dyn.s.cm-5 | Standard Error 83.09 |
| JNJ-39588146 | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Calculated Systemic Vascular Resistance (SVR) | 3 hour infusion (30 ng/kg/min) | -245.98 dyn.s.cm-5 | Standard Error 93.74 |
Comparison: 95% confidence intervals and p values represent the placebo-subtracted LS mean change from baseline in SVR at the end of the 5 ng/kg/min dose.p-value: 0.05195% CI: [-529.875, 1.147]ANCOVA
Comparison: 95% confidence intervals and p values represent the placebo-subtracted LS mean change from baseline in SVR at the end of the 15 ng/kg/min dose.p-value: 0.000695% CI: [-592.781, -173.867]ANCOVA
Comparison: 95% confidence intervals and p values represent the placebo-subtracted LS mean change from baseline in SVR at the end of the 30 ng/kg/min dose.p-value: 0.000195% CI: [-764.07, -291.478]ANCOVA
Secondary
Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Diastolic Blood Pressure (DBP)
The primary analysis of this study focused on the differences between the treatment groups in terms of LS mean change from Baseline at each time point; thus, the results provided below consist of the JNJ-39588146 minus placebo differences in Least Square (LS) means (and associated confidence intervals) for change from Baseline in diastolic blood pressure(DBP) at each time point as well as treatment group LS means and Standard Errors.
Time frame: Baseline up through 3 hours post infusion initiation
Population: The modified intent-to-treat (MITT) population included all randomized patients who received at least 1 dose of study drug, had baseline measurement and at least 1 post-baseline measurement value of at least 1 of the primary endpoints. The efficacy analysis was to be performed using the MITT analysis set.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Diastolic Blood Pressure (DBP) | 1 hour infusion (5 ng/kg/min) | -0.43 mmHg | Standard Error 2.57 |
| Placebo | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Diastolic Blood Pressure (DBP) | 2 hour infusion (15 ng/kg/min) | 1.83 mmHg | Standard Error 2.7 |
| Placebo | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Diastolic Blood Pressure (DBP) | 3 hour infusion (30 ng/kg/min) | 3.05 mmHg | Standard Error 2.6 |
| JNJ-39588146 | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Diastolic Blood Pressure (DBP) | 1 hour infusion (5 ng/kg/min) | -3.78 mmHg | Standard Error 1.83 |
| JNJ-39588146 | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Diastolic Blood Pressure (DBP) | 2 hour infusion (15 ng/kg/min) | -3.72 mmHg | Standard Error 1.93 |
| JNJ-39588146 | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Diastolic Blood Pressure (DBP) | 3 hour infusion (30 ng/kg/min) | -4.03 mmHg | Standard Error 1.86 |
Comparison: 95% confidence intervals and p values represent the placebo-subtracted LS mean change from baseline in diastolic blood pressure (DBP) at the end of the 5 ng/kg/min dose.p-value: 0.156195% CI: [-8.047, 1.331]ANCOVA
Comparison: 95% confidence intervals and p values represent the placebo-subtracted LS mean change from baseline in diastolic blood pressure (DBP) at the end of the 15 ng/kg/min dose.p-value: 0.028295% CI: [-10.482, -0.622]ANCOVA
Comparison: 95% confidence intervals and p values represent the placebo-subtracted LS mean change from baseline in diastolic blood pressure (DBP) at the end of the 30 ng/kg/min dose.p-value: 0.004395% CI: [-11.818, -2.332]ANCOVA
Secondary
Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Heart Rate (HR)
The primary analysis of this study focused on the differences between the treatment groups in terms of Least Squares (LS) mean change from Baseline at each time point; thus, the results provided below consist of the JNJ-39588146 minus placebo differences in LS means (and associated confidence intervals) for change from Baseline in heart rate (HR) at each time point as well as treatment group LS means and Standard Errors.
Time frame: At 1-hour, 2 hours and 3 hours post infusion initiation
Population: The modified intent-to-treat (MITT) population included all randomized patients who received at least 1 dose of study drug, had baseline measurement and at least 1 post-baseline measurement value of at least 1 of the primary endpoints. The efficacy analysis was to be performed using the MITT analysis set.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Heart Rate (HR) | 1 hour infusion (5 ng/kg/min) | 3.02 beats per minute (bpm) | Standard Error 1.24 |
| Placebo | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Heart Rate (HR) | 2 hour infusion (15 ng/kg/min) | 3.72 beats per minute (bpm) | Standard Error 1.69 |
| Placebo | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Heart Rate (HR) | 3 hour infusion (30 ng/kg/min) | 3.07 beats per minute (bpm) | Standard Error 1.81 |
| JNJ-39588146 | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Heart Rate (HR) | 1 hour infusion (5 ng/kg/min) | 2.69 beats per minute (bpm) | Standard Error 0.91 |
| JNJ-39588146 | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Heart Rate (HR) | 2 hour infusion (15 ng/kg/min) | 4.96 beats per minute (bpm) | Standard Error 1.24 |
| JNJ-39588146 | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Heart Rate (HR) | 3 hour infusion (30 ng/kg/min) | 5.23 beats per minute (bpm) | Standard Error 1.32 |
Comparison: 95% confidence intervals and p values represent the placebo-subtracted LS mean change from baseline in heart rate (HR) at the end of the 5 ng/kg/min dose.p-value: 0.768295% CI: [-2.527, 1.879]ANCOVA
Comparison: 95% confidence intervals and p values represent the placebo-subtracted LS mean change from baseline in heart rate (HR) at the end of the 15 ng/kg/min dose.p-value: 0.410795% CI: [-1.764, 4.235]ANCOVA
Comparison: 95% confidence intervals and p values represent the placebo-subtracted LS mean change from baseline in heart rate (HR) at the end of the 30 ng/kg/min dose.p-value: 0.181195% CI: [-1.046, 5.372]ANCOVA
Secondary
Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Pulmonary Arterial Diastolic Pressure (PADP)
The primary analysis of this study focused on the differences between the treatment groups in terms of Least Square (LS) mean change from Baseline at each time point; thus, the results provided below consist of the JNJ-39588146 minus placebo differences in LS means (and associated confidence intervals) for change from Baseline in Pulmonary Arterial Diastolic Pressure (PADP) at the end of 5, 15 and 30 ng/kg/min Infusions as well as treatment group LS means and Standard Errors.
Time frame: Baseline up through 3 hours post infusion initiation
Population: The modified intent-to-treat (MITT) population included all randomized patients who received at least 1 dose of study drug, had baseline measurement and at least 1 post-baseline measurement value of at least 1 of the primary endpoints. The efficacy analysis was to be performed using the MITT analysis set.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Pulmonary Arterial Diastolic Pressure (PADP) | 1 hour infusion (5 ng/kg/min) | -0.99 mmHg | Standard Error 1.57 |
| Placebo | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Pulmonary Arterial Diastolic Pressure (PADP) | 2 hour infusion (15 ng/kg/min) | -0.83 mmHg | Standard Error 1.91 |
| Placebo | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Pulmonary Arterial Diastolic Pressure (PADP) | 3 hour infusion (30 ng/kg/min) | -0.72 mmHg | Standard Error 1.85 |
| JNJ-39588146 | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Pulmonary Arterial Diastolic Pressure (PADP) | 1 hour infusion (5 ng/kg/min) | -0.29 mmHg | Standard Error 1.12 |
| JNJ-39588146 | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Pulmonary Arterial Diastolic Pressure (PADP) | 2 hour infusion (15 ng/kg/min) | -1.17 mmHg | Standard Error 1.36 |
| JNJ-39588146 | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Pulmonary Arterial Diastolic Pressure (PADP) | 3 hour infusion (30 ng/kg/min) | -1.46 mmHg | Standard Error 1.32 |
Comparison: 95% confidence intervals and p values represent the placebo-subtracted LS mean change from baseline in PADP at the end of the 5 ng/kg/min dose.p-value: 0.630495% CI: [-2.197, 3.588]ANCOVA
Comparison: 95% confidence intervals and p values represent the placebo-subtracted LS mean change from baseline in PADP at the end of the 15 ng/kg/min dose.p-value: 0.84295% CI: [-3.851, 3.153]ANCOVA
Comparison: 95% confidence intervals and p values represent the placebo-subtracted LS mean change from baseline in PADP at the end of the 30 ng/kg/min dose.p-value: 0.665895% CI: [-4.138, 2.669]ANCOVA
Secondary
Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Pulmonary Arterial Systolic Pressure (PASP)
The primary analysis of this study focused on the differences between the treatment groups in terms of Least Squares (LS) mean change from Baseline at each time point; thus, the results provided below consist of the JNJ-39588146 minus placebo differences in LS means (and associated confidence intervals) for change from Baseline in Pulmonary Arterial Systolic Pressure (PASP) at the end of 5, 15 and 30 ng/kg/min Infusions as well as treatment group LS means and Standard Errors.
Time frame: Baseline up through 3 hours post infusion initiation
Population: The modified intent-to-treat (MITT) population included all randomized patients who received at least 1 dose of study drug, had baseline measurement and at least 1 post-baseline measurement value of at least 1 of the primary endpoints. The efficacy analysis was to be performed using the MITT analysis set.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Pulmonary Arterial Systolic Pressure (PASP) | 1 hour infusion (5 ng/kg/min) | 2.69 mmHg | Standard Error 2.1 |
| Placebo | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Pulmonary Arterial Systolic Pressure (PASP) | 2 hour infusion (15 ng/kg/min) | 0.51 mmHg | Standard Error 2.45 |
| Placebo | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Pulmonary Arterial Systolic Pressure (PASP) | 3 hour infusion (30 ng/kg/min) | -0.79 mmHg | Standard Error 2.74 |
| JNJ-39588146 | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Pulmonary Arterial Systolic Pressure (PASP) | 1 hour infusion (5 ng/kg/min) | 1.32 mmHg | Standard Error 1.55 |
| JNJ-39588146 | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Pulmonary Arterial Systolic Pressure (PASP) | 2 hour infusion (15 ng/kg/min) | -0.48 mmHg | Standard Error 1.8 |
| JNJ-39588146 | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Pulmonary Arterial Systolic Pressure (PASP) | 3 hour infusion (30 ng/kg/min) | 0.24 mmHg | Standard Error 2.02 |
Comparison: 95% confidence intervals and p values represent the placebo-subtracted LS mean change from baseline in PASP at the end of the 5 ng/kg/min dose.p-value: 0.484195% CI: [-5.308, 2.554]ANCOVA
Comparison: 95% confidence intervals and p values represent the placebo-subtracted LS mean change from baseline in SV at the end of the 15 ng/kg/min dose.p-value: 0.666595% CI: [-5.567, 3.594]ANCOVA
Comparison: 95% confidence intervals and p values represent the placebo-subtracted LS mean change from baseline in PASP at the end of the 30 ng/kg/min dose.p-value: 0.690495% CI: [-4.107, 6.148]ANCOVA
Secondary
Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Stroke Volume (SV)
The primary analysis of this study focused on the differences between the treatment groups in terms of Least Squares (LS) mean change from Baseline at each time point; thus, the results provided below consist of the JNJ-39588146 minus placebo differences in LS means (and associated confidence intervals) for change from Baseline in Stroke Volume (SV) at the end of the 30 ng/kg/min infusion as well as treatment group LS means and Standard Errors.
Time frame: Baseline up through 3 hours post infusion initiation
Population: The modified intent-to-treat (MITT) population included all randomized patients who received at least 1 dose of study drug, had baseline measurement and at least 1 post-baseline measurement value of at least 1 of the primary endpoints. The efficacy analysis was to be performed using the MITT analysis set.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Stroke Volume (SV) | 1 hour infusion (5 ng/kg/min) | -1.34 mL/beat | Standard Error 6.51 |
| Placebo | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Stroke Volume (SV) | 2 hour infusion (15 ng/kg/min) | -4.33 mL/beat | Standard Error 6.23 |
| Placebo | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Stroke Volume (SV) | 3 hour infusion (30 ng/kg/min) | -0.62 mL/beat | Standard Error 6.7 |
| JNJ-39588146 | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Stroke Volume (SV) | 1 hour infusion (5 ng/kg/min) | 5.75 mL/beat | Standard Error 4.84 |
| JNJ-39588146 | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Stroke Volume (SV) | 2 hour infusion (15 ng/kg/min) | 4.45 mL/beat | Standard Error 4.63 |
| JNJ-39588146 | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Stroke Volume (SV) | 3 hour infusion (30 ng/kg/min) | 13.54 mL/beat | Standard Error 4.98 |
Comparison: 95% confidence intervals and p values represent the placebo-subtracted LS mean change from baseline in SV at the end of the 5 ng/kg/min dose.p-value: 0.212395% CI: [-4.198, 18.359]ANCOVA
Comparison: 95% confidence intervals and p values represent the placebo-subtracted LS mean change from baseline in SV at the end of the 15 ng/kg/min dose.p-value: 0.108395% CI: [-2.016, 19.575]ANCOVA
Comparison: 95% confidence intervals and p values represent the placebo-subtracted LS mean change from baseline in SV at the end of the 30 ng/kg/min dose.p-value: 0.01895% CI: [2.557, 25.771]ANCOVA
Secondary
Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Systolic Blood Pressure (SBP)
The primary analysis of this study focused on the differences between the treatment groups in terms of Least Squares (LS) mean change from Baseline at each time point; thus, the results provided below consist of the JNJ-39588146 minus placebo differences in LS means (and associated confidence intervals) for change from Baseline in systolic blood pressure (SBP) at each time point as well as treatment group LS means and Standard Errors.
Time frame: Baseline up through 3 hours post infusion initiation
Population: The modified intent-to-treat (MITT) population included all randomized patients who received at least 1 dose of study drug, had baseline measurement and at least 1 post-baseline measurement value of at least 1 of the primary endpoints. The efficacy analysis was to be performed using the MITT analysis set.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Systolic Blood Pressure (SBP) | 1 hour infusion (5 ng/kg/min) | 0.15 mmHg | Standard Error 2.95 |
| Placebo | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Systolic Blood Pressure (SBP) | 2 hour infusion (15 ng/kg/min) | 6.94 mmHg | Standard Error 3.17 |
| Placebo | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Systolic Blood Pressure (SBP) | 3 hour infusion (30 ng/kg/min) | 6.32 mmHg | Standard Error 4.09 |
| JNJ-39588146 | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Systolic Blood Pressure (SBP) | 1 hour infusion (5 ng/kg/min) | -0.53 mmHg | Standard Error 2.12 |
| JNJ-39588146 | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Systolic Blood Pressure (SBP) | 2 hour infusion (15 ng/kg/min) | 4.94 mmHg | Standard Error 2.28 |
| JNJ-39588146 | Post-baseline Changes Compared to Placebo (at 1-, 2-, and 3-hours Post Infusion Initiation [ie, at the End of 5, 15 and 30 ng/kg/Min Infusions]) in Systolic Blood Pressure (SBP) | 3 hour infusion (30 ng/kg/min) | 2.55 mmHg | Standard Error 2.94 |
Comparison: 95% confidence intervals and p values represent the placebo-subtracted LS mean change from baseline in systolic blood pressure (SBP) at the end of the 5 ng/kg/min dose.p-value: 0.80395% CI: [-6.06, 4.718]ANCOVA
Comparison: 95% confidence intervals and p values represent the placebo-subtracted LS mean change from baseline in systolic blood pressure (SBP) at the end of the 15 ng/kg/min dose.p-value: 0.492395% CI: [-7.781, 3.801]ANCOVA
Comparison: 95% confidence intervals and p values represent the placebo-subtracted LS mean change from baseline in systolic blood pressure (SBP) at the end of the 30 ng/kg/min dose.p-value: 0.315295% CI: [-11.251, 3.708]ANCOVA
Secondary
Post-baseline Changes Compared to Placebo (at 3-hours Post Infusion Initiation [ie, at the End of 30 ng/kg/Min Infusion]) in Left Ventricular End Diastolic Volume (LVEDV)
The primary analysis of this study focused on the differences between the treatment groups in terms of Least Squares (LS) mean change from Baseline at each time point; thus, the results provided below consist of the JNJ-39588146 minus placebo differences in LS means (and associated confidence intervals) for change from Baseline in Left Ventricular End Diastolic Volume (LVEDV) at the end of the 30 ng/kg/min infusion as well as treatment group LS means and Standard Errors.
Time frame: Baseline up through 3 hours post infusion initiation
Population: The modified intent-to-treat (MITT) population included all randomized patients who received at least 1 dose of study drug, had baseline measurement and at least 1 post-baseline measurement value of at least 1 of the primary endpoints. The efficacy analysis was to be performed using the MITT analysis set.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Post-baseline Changes Compared to Placebo (at 3-hours Post Infusion Initiation [ie, at the End of 30 ng/kg/Min Infusion]) in Left Ventricular End Diastolic Volume (LVEDV) | -13.91 mL | Standard Error 10.05 |
| JNJ-39588146 | Post-baseline Changes Compared to Placebo (at 3-hours Post Infusion Initiation [ie, at the End of 30 ng/kg/Min Infusion]) in Left Ventricular End Diastolic Volume (LVEDV) | -11.93 mL | Standard Error 7.11 |
Comparison: 95% confidence intervals and p values represent the placebo-subtracted LS mean change from baseline in LVEDV at the end of the 30 ng/kg/min dose.p-value: 0.829795% CI: [-16.592, 20.551]ANCOVA
Secondary
Post-baseline Changes Compared to Placebo (at 3-hours Post Infusion Initiation [ie, at the End of the 30 ng/kg/Min Infusion]) in Fractional Shortening (FS)
The primary analysis of this study focused on the differences between the treatment groups in terms of Least Squares (LS) mean change from Baseline at each time point; thus, the results provided below consist of the JNJ-39588146 minus placebo differences in LS means (and associated confidence intervals) for change from Baseline in Fractional Shortening (FS) at the end of the 30 ng/kg/min infusion as well as treatment group LS means and Standard Errors.
Time frame: Baseline up through 3 hours post infusion initiation
Population: The modified intent-to-treat (MITT) population included all randomized patients who received at least 1 dose of study drug, had baseline measurement and at least 1 post-baseline measurement value of at least 1 of the primary endpoints. The efficacy analysis was to be performed using the MITT analysis set.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Post-baseline Changes Compared to Placebo (at 3-hours Post Infusion Initiation [ie, at the End of the 30 ng/kg/Min Infusion]) in Fractional Shortening (FS) | 0.22 percentage | Standard Error 1.54 |
| JNJ-39588146 | Post-baseline Changes Compared to Placebo (at 3-hours Post Infusion Initiation [ie, at the End of the 30 ng/kg/Min Infusion]) in Fractional Shortening (FS) | 1.17 percentage | Standard Error 1.14 |
Comparison: 95% confidence intervals and p values represent the placebo-subtracted LS mean change from baseline in FS at the end of the 30 ng/kg/min dose.p-value: 0.374895% CI: [-1.204, 3.102]ANCOVA
Secondary
Post-baseline Changes Compared to Placebo (at 3-hours Post Infusion Initiation [ie, at the End of the 30 ng/kg/Min Infusion]) in Left Ventricular Ejection Fraction (LVEF)
The primary analysis of this study focused on the differences between the treatment groups in terms of Least Squares (LS) mean change from Baseline at each time point; thus, the results provided below consist of the JNJ-39588146 minus placebo differences in LS means (and associated confidence intervals) for change from Baseline in Left Ventricular Ejection Fraction (LVEF) at the end of the 30 ng/kg/min infusion as well as treatment group LS means and Standard Errors.
Time frame: Baseline up through 3 hours post infusion initiation
Population: The modified intent-to-treat (MITT) population included all randomized patients who received at least 1 dose of study drug, had baseline measurement and at least 1 post-baseline measurement value of at least 1 of the primary endpoints. The efficacy analysis was to be performed using the MITT analysis set.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Post-baseline Changes Compared to Placebo (at 3-hours Post Infusion Initiation [ie, at the End of the 30 ng/kg/Min Infusion]) in Left Ventricular Ejection Fraction (LVEF) | 3.61 percentage | Standard Error 1.93 |
| JNJ-39588146 | Post-baseline Changes Compared to Placebo (at 3-hours Post Infusion Initiation [ie, at the End of the 30 ng/kg/Min Infusion]) in Left Ventricular Ejection Fraction (LVEF) | 3.92 percentage | Standard Error 1.38 |
Comparison: 95% confidence intervals and p values represent the placebo-subtracted LS mean change from baseline in LVEF at the end of the 30 ng/kg/min dose.p-value: 0.86595% CI: [-3.352, 3.968]ANCOVA
Secondary
Post-baseline Changes Compared to Placebo (at 3-hours Post Infusion Initiation [ie, at the End of the 30 ng/kg/Min Infusion]) in Left Ventricular End Systolic Volume (LVESV)
The primary analysis of this study focused on the differences between the treatment groups in terms of Least Squares (LS) mean change from Baseline at each time point; thus, the results provided below consist of the JNJ-39588146 minus placebo differences in LS means (and associated confidence intervals) for change from Baseline in left ventricular end systolic volume (LVESV) at the end of the 30 ng/kg/min infusion as well as treatment group LS means and Standard Errors.
Time frame: Baseline up through 3 hours post infusion initiation
Population: The modified intent-to-treat (MITT) population included all randomized patients who received at least 1 dose of study drug, had baseline measurement and at least 1 post-baseline measurement value of at least 1 of the primary endpoints. The efficacy analysis was to be performed using the MITT analysis set.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Post-baseline Changes Compared to Placebo (at 3-hours Post Infusion Initiation [ie, at the End of the 30 ng/kg/Min Infusion]) in Left Ventricular End Systolic Volume (LVESV) | -15.51 mL | Standard Error 8.93 |
| JNJ-39588146 | Post-baseline Changes Compared to Placebo (at 3-hours Post Infusion Initiation [ie, at the End of the 30 ng/kg/Min Infusion]) in Left Ventricular End Systolic Volume (LVESV) | -15.28 mL | Standard Error 6.36 |
Comparison: 95% confidence intervals and p values represent the placebo-subtracted LS mean change from baseline in left ventricular end systolic volume (LVESV) at the end of the 30 ng/kg/min dose.p-value: 0.976995% CI: [-16.347, 16.823]ANCOVA