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

NCT ID: NCT01120210

Last Updated: 2013-07-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-30
• Study Completion Date: 2011-09-30

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.

Conditions

Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Part 1 (Main Study)

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

Group Type: EXPERIMENTAL

JNJ-39588146 5 ng/kg/min

Intervention Type: DRUG

1-hour infusion of JNJ-39588146 5 ng/kg/min on Day 1

JNJ-39588146 15 ng/kg/min

Intervention Type: DRUG

1-hour infusion of JNJ-39588146 15 ng/kg/min on Day 1

JNJ-39588146 30 ng/kg/min

Intervention Type: DRUG

1-hour infusion of JNJ-39588146 30 ng/kg/min on Day 1

Placebo

Intervention Type: DRUG

1-hour infusion of matching placebo on Day 1

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

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

1-hour infusion of matching placebo on Day 1

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

Intervention Type: DRUG

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.

Interventions

JNJ-39588146 5 ng/kg/min

1-hour infusion of JNJ-39588146 5 ng/kg/min on Day 1

Intervention Type: DRUG

JNJ-39588146 15 ng/kg/min

1-hour infusion of JNJ-39588146 15 ng/kg/min on Day 1

Intervention Type: DRUG

JNJ-39588146 30 ng/kg/min

1-hour infusion of JNJ-39588146 30 ng/kg/min on Day 1

Intervention Type: DRUG

Placebo

1-hour infusion of matching placebo on Day 1

Intervention Type: 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.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 86 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial

Role: STUDY_DIRECTOR

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Locations

Aalst, , Belgium

B-1070 Bruxelles, , Belgium

Genk, , Belgium

Bad Nauheim, , Germany

Hamburg, , Germany

Warsaw, , Poland

Wroclaw, , Poland

Bucharest, , Romania

Tg. Mures, , Romania

Countries

Belgium; Germany; Poland; Romania

References

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.

Reference Type: DERIVED

PMID: 23471413 (View on PubMed)

Other Identifiers

39588146AHF2001

Identifier Type: OTHER

Identifier Source: secondary_id

2009-013929-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR017116

Identifier Type: -

Identifier Source: org_study_id

NCT01678768

Identifier Type: -

Identifier Source: nct_alias