A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Investigate the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of JNJ-39588146 in Subjects With Heart Failure
Overview
- Phase
- Phase 2
- Intervention
- JNJ-39588146 30 ng/kg/min
- Conditions
- Heart Failure
- Sponsor
- Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
- Enrollment
- 62
- Primary Endpoint
- 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)
- Status
- Completed
- Last Updated
- 12 years ago
Overview
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.
Investigators
Eligibility Criteria
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.
Arms & Interventions
Part 1 (Main Study)
3 consecutive 1-hour infusions of JNJ-39588146 5, 15, or 30 ng/kg/min or matching placebo
Intervention: JNJ-39588146 30 ng/kg/min
Part 1 (Main Study)
3 consecutive 1-hour infusions of JNJ-39588146 5, 15, or 30 ng/kg/min or matching placebo
Intervention: JNJ-39588146 5 ng/kg/min
Part 1 (Main Study)
3 consecutive 1-hour infusions of JNJ-39588146 5, 15, or 30 ng/kg/min or matching placebo
Intervention: JNJ-39588146 15 ng/kg/min
Part 1 (Main Study)
3 consecutive 1-hour infusions of JNJ-39588146 5, 15, or 30 ng/kg/min or matching placebo
Intervention: Placebo
Part 2 (Extended Infusion Sub-Study)
1 18-hr infusion of JNJ-39588146 of the highest tolerated dose from Part 1 of the study or matching placebo
Intervention: Placebo
Part 2 (Extended Infusion Sub-Study)
1 18-hr infusion of JNJ-39588146 of the highest tolerated dose from Part 1 of the study or matching placebo
Intervention: JNJ-39588146 5, 15, or 30 ng/kg/min
Outcomes
Primary Outcomes
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)
Time Frame: 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)
Time Frame: 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 Outcomes
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)