A Study to Investigate the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of an Intravenous Solution of JNJ-39588146 or Placebo in Patients With Heart Failure

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

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.

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Drug: JNJ-39588146 5 ng/kg/min; Drug: JNJ-39588146 15 ng/kg/min; Drug: JNJ-39588146 30 ng/kg/min; Drug: Placebo; Drug: JNJ-39588146 5, 15, or 30 ng/kg/min

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.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Aalst, Belgium
  • B-1070 Bruxelles, Belgium
  • Genk, Belgium
• Germany
  • Bad Nauheim, Germany
  • Hamburg, Germany
• Poland
  • Warszawa, Poland
  • Wroclaw, Poland
• Romania
  • Bucuresti, Romania
  • Tg. Mures, Romania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 86 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Part 1 (Main Study); 3 consecutive 1-hour infusions of JNJ-39588146 5, 15, or 30 ng/kg/min or matching placebo	Drug: JNJ-39588146 5 ng/kg/min; 1-hour infusion of JNJ-39588146 5 ng/kg/min on Day 1; Drug: JNJ-39588146 15 ng/kg/min; 1-hour infusion of JNJ-39588146 15 ng/kg/min on Day 1; Drug: JNJ-39588146 30 ng/kg/min; 1-hour infusion of JNJ-39588146 30 ng/kg/min on Day 1; Drug: Placebo; 1-hour infusion of matching placebo on Day 1
EXPERIMENTAL: 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	Drug: Placebo; 1-hour infusion of matching placebo on Day 1; Drug: JNJ-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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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 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.	Baseline up through 3 hours post infusion initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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)	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.	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)	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.	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)	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.	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)	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.	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)	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.	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)	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.	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)	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.	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)	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.	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)	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.	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)	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.	Baseline up through 3 hours post infusion initiation

Collaborators and Investigators

• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Publications and helpful links

General Publications

• Gheorghiade M, Greene SJ, Ponikowski P, Maggioni AP, Korewicki J, Macarie C, Metra M, Grzybowski J, Bubenek-Turconi SI, Radziszewski W, Olson A, Bueno OF, Ghosh A, Deckelbaum LI, Li LY, Patel AR, Koester A, Konstam MA. Haemodynamic effects, safety, and pharmacokinetics of human stresscopin in heart failure with reduced ejection fraction. Eur J Heart Fail. 2013 Jun;15(6):679-89. doi: 10.1093/eurjhf/hft023. Epub 2013 Mar 6.

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (ACTUAL): September 1, 2011
• Study Completion (ACTUAL): September 1, 2011

Study Registration Dates

• First Submitted: May 6, 2010
• First Submitted That Met QC Criteria: May 7, 2010
• First Posted (ESTIMATE): May 10, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): July 19, 2013
• Last Update Submitted That Met QC Criteria: July 8, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: Heart Failure; Cardiac Failure
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: CR017116; 39588146AHF2001 (OTHER: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.); 2009-013929-42 (EUDRACT_NUMBER)