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

Johnson & Johnson (J&J)

Status and phase: Completed; Phase 2

Conditions: Heart Failure

Treatments: Drug: Placebo; Drug: JNJ-39588146 30 ng/kg/min; Drug: JNJ-39588146 5 ng/kg/min; Drug: JNJ-39588146 5, 15, or 30 ng/kg/min; Drug: JNJ-39588146 15 ng/kg/min

Study type: Interventional

Funder types: Industry

Identifiers

NCT01120210

CR017116

2009-013929-42 (EudraCT Number)

39588146AHF2001 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 62 patients

Sex: All

Ages: 18 to 86 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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62 participants in 2 patient groups

Part 1 (Main Study)

Experimental group

Description:

3 consecutive 1-hour infusions of JNJ-39588146 5, 15, or 30 ng/kg/min or matching placebo

Treatment:

Drug: JNJ-39588146 30 ng/kg/min

Drug: Placebo

Drug: JNJ-39588146 5 ng/kg/min

Drug: JNJ-39588146 15 ng/kg/min

Part 2 (Extended Infusion Sub-Study)

Experimental group

Description:

1 18-hr infusion of JNJ-39588146 of the highest tolerated dose from Part 1 of the study or matching placebo

Treatment:

Drug: JNJ-39588146 5, 15, or 30 ng/kg/min

Drug: Placebo