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

NCT01120210 | Completed Phase 2 Results DMC

• 3 other identifiers: CR01711639588146AHF20012009-013929-42
• Study Type: interventional
• Target: 62
• Locations: 4 countries
• Sites: 9

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.

Conditions

Heart Failure

Keywords

Heart Failure; Cardiac Failure

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (11)

• 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

Study Arms (2)

Part 1 (Main Study)

EXPERIMENTAL

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; Drug: JNJ-39588146 15 ng/kg/min; Drug: JNJ-39588146 30 ng/kg/min; Drug: Placebo

Part 2 (Extended Infusion Sub-Study)

EXPERIMENTAL

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

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

Interventions

JNJ-39588146 5 ng/kg/min DRUG

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

Part 1 (Main Study)

JNJ-39588146 15 ng/kg/min DRUG

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

Part 1 (Main Study)

JNJ-39588146 30 ng/kg/min DRUG

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

Part 1 (Main Study)

Placebo DRUG

1-hour infusion of matching placebo on Day 1

Part 1 (Main Study); Part 2 (Extended Infusion Sub-Study)

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

Part 2 (Extended Infusion Sub-Study)

Eligibility Criteria

• Age: 18 Years - 86 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (9)

Unknown Facility

Aalst, Belgium

Location

Unknown Facility

B-1070 Bruxelles, Belgium

Location

Unknown Facility

Genk, Belgium

Location

Unknown Facility

Bad Nauheim, Germany

Location

Unknown Facility

Hamburg, Germany

Location

Unknown Facility

Warsaw, Poland

Location

Unknown Facility

Wroclaw, Poland

Location

Unknown Facility

Bucharest, Romania

Location

Unknown Facility

Tg. Mures, Romania

Location

Related Publications (1)

• 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.

  PMID: 23471413 DERIVED

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Limitations and Caveats

Data from the extended infusion sub-study were exploratory; therefore, results for outcome measures from the sub-study are not reported.

Results Point of Contact

• Title: Senior Director Translational Medicine
• Organization: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

wradzisz@its.jnj.com

858.320.3408

Study Officials

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

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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2010
• First Posted: May 10, 2010
• Study Start: June 1, 2010
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: July 19, 2013
• Results First Posted: June 25, 2013

Record last verified: 2013-07

Locations

RO (2); PL (2); DE (2); BE (3)