A Study of Ularitide in the Treatment of Subjects With Acute Decompensated Heart Failure

NCT00487799 | Withdrawn Phase 1 DMC

• 1 other identifier: Ularitide-1503
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 8

Brief Summary

To determine the maximum tolerated dose (MTD) of ularitide in the treatment of subjects hospitalized with symptomatic acute decompensated heart failure (ADHF).

Conditions

Heart Failure, Congestive

Keywords

Acute Decompensated Heart Failure; ADHF; Heart Failure

Outcome Measures

Primary Outcomes (1)

• The MTD of ularitide infused over 48 hours.

Secondary Outcomes (5)

• Frequency, severity, and relationship of AEs and serious adverse events (SAEs) to study drug through Day 32 (ie, 30 days following the end of study drug infusion).

• Physical examinations, vital signs, electrocardiography, and clinical laboratory values through 48 hours.

• Decline in renal function defined as a >25% rise or a 0.3 mg/dL increase in serum creatinine from pre-dose at baseline to 48 hours post the end of infusion and through Day 32.

• Pharmacokinetic profile including Css, AUC, CL, V, and t½ up to 2 hours post end of infusion.

• Incidence of ularitide-specific anti-drug antibodies (ADAb) through Day 32.

Interventions

Ularitide DRUG

Eligibility Criteria

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

You may qualify if:

• Males and females who are 18 years or older.
• Unplanned hospitalization for ADHF.
• Randomization should occur as soon as possible from presentation to emergency department or hospital for ADHF up to 24 hours from admission.
• Dyspnea at rest as assessed by the subject not more than 1 hour prior to randomization. Subjects must have the ability to interpret and report self-assessed dyspnea.
• At least 1 of the following 2 criteria:
• Prior medical history of CHF (eg, prior hospitalization for CHF or left ventricular ejection fraction \<40%, as determined by transthoracic echocardiography at the time of screening or previously determined and documented in the patient's chart as follows):
• Within the previous 6 months in subjects with unstable symptoms, or
• Within the previous 12 months in subjects with stable symptoms.
• Clinical evidence (at screening) of heart failure, including abnormal jugular venous pressure (JVP) (eg, \>8 cm above the clavicle, assessed at 45°angle), rales or crackles more than a third above bases, or 2+ lower extremity edema.
• On optimal background therapy for ADHF (as determined by the investigator); subjects are required to have received, at a minimum, at least 1 hour of oxygen supplementation and at least one dose of IV furosemide at a minimum dose of 40 mg with the last bolus being delivered \>2 hours before study drug administration is initiated (or another diuretic at a comparable dose; eg, 2 mg bumetanide or 20 mg torsemide, with the last bolus being delivered \>4 hours before study drug administration is initiated.
• If subject received IV opiate, the last dose must have been \>3 hours before administration of study drug.
• Women of childbearing potential must have a negative pregnancy test prior to being randomized in the study. Women and men of reproductive potential will agree to utilize effective contraception during the entire treatment period and for 1 month after receiving the last dose of ularitide or placebo.
• Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local subject privacy regulations).

You may not qualify if:

• Any subject will be ineligible for this study if any one of the following criteria is met:
• Breathing rate \<18 breaths per minute (measured during 60 seconds).
• A systolic blood pressure (SBP) \<110 mmHg or \>180 mmHg within an hour before randomization, or SBP \<120 mmHg for subjects receiving IV inotropics or vasodilators. A SBP \<90 mmHg in two successive measurements within 30 minutes before randomization. (Subjects on baseline IV inotropes or vasodilators must be on a stable dose for ³3 hours prior to randomization.)
• BNP \<400 pg/mL or NT?pro-BNP \<1200 pg/mL anytime from initial presentation to hospital to time of randomization.
• Use of IV contrast material within 48 hours before infusion of study drug.
• History of central or peripheral neurological ischemic disorder (stroke, etc.).
• Active myocarditis, obstructive hypertrophic cardiomyopathy, congenital heart disease, restrictive cardiomyopathy, constrictive pericarditis, severe aortic stenosis, uncorrected primary valvular disease, or significant obstructive valve disease.
• Acute decompensated heart failure associated with endocrine (eg, thyroid storm), metabolic, or drug-related toxicity.
• Elevation of serum creatinine?kinase myocardial band (CK?MB) or cardiac troponin (Troponin I) \>2 times the upper limit of normal within 6 hours prior to randomization.
• Active, ongoing myocardial ischemia, hospitalization for acute myocardial infarction, or administration of thrombolytic therapy in the last 30 days prior to randomization, or, any ECG abnormalities in the opinion of the investigator, suggestive of active ischemic changes.
• Percutaneous coronary intervention, coronary artery bypass graft surgery, other cardiac surgery, or major noncardiac surgery within 90 days prior to randomization.
• Any cardiogenic shock (SBP \<90 mmHg with signs or symptoms of organ hypoperfusion) from initial presentation to randomization.
• Any significant volume depletion or severe electrolyte imbalance.
• Renal disorder with a creatinine clearance \<30 mL/min, as calculated by the Cockcroft-Gault equation at screening.
• Use of a phosphodiesterase type 5 (PDE 5) inhibitor such as sildenafil within 72 hours prior to randomization.

Sponsors & Collaborators

• Facet Biotech: lead

Study Sites (8)

UCSD Medical Center

San Diego, California, 92103, United States

Location

The Atlanta Cardiology Group, PC

Atlanta, Georgia, 30342, United States

Location

Feinberg School of Medicine, Northwestern Univ.

Chicago, Illinois, 60611, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Cardiovascular Specialists PC dba New York Heart Ctr.

Syracuse, New York, 13210, United States

Location

Albert Einstein Medical Center

Philadelphia, Pennsylvania, 19141, United States

Location

Kore Cardiovascular Research Institute

Lexington, Tennessee, 38351, United States

Location

MeSH Terms

Conditions

Heart Failure

Interventions

Ularitide

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• William Cotts, MD

  Feinberg School of Medicine, Northwestern Univ.

  PRINCIPAL INVESTIGATOR

• Gregory Ewald, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

• Daniel Fuleihan, MD

  Cardiovascular Specialists PC dba New York Heart Ctr

  PRINCIPAL INVESTIGATOR

• Barry Greenberg, MD

  UCSD Medical Center

  PRINCIPAL INVESTIGATOR

• Darshak Karia, MD

  Albert Einstein Medical Center

  PRINCIPAL INVESTIGATOR

• Elie Korban, MD

  Kore Cardiovascular Research Institute

  PRINCIPAL INVESTIGATOR

• Richard Nowak, MD

  Henry Ford Health System

  PRINCIPAL INVESTIGATOR

• Nirav Y. Raval, MD

  The Atlanta Cardiology Group, PC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: June 15, 2007
• First Posted: June 19, 2007
• Last Updated: July 20, 2009

Record last verified: 2009-07

Locations

US (8)