Acute decompensated heart failure MedDRA version: 8.1 Level: LLT Classification code 10000803 Term: Acute heart failure
Conditions
Interventions
Product Name: Ularitide
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: ularitide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Phar
Sponsors
PDL BioPharma Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Males and females = 18 years. 2) Unplanned hospitalization for ADHF. 3)Randomization within 24 hours after presentation to emergency department or hospital for ADHF. 4) Dyspnea at rest as assessed by the subject. Subject must have the ability to interpret and report self-assessed dyspnea 5) At least 1 of the following 2 criteria: •Prior medical history of CHF (eg, prior hospitalization for CHF) or left ventricular ejection fraction 8 cm above the clavicle, assessed at 45°angle), rales or crackles more than a third above bases, or 2+ lower extremity edema. 6) Radiographic evidence (at screening) of pulmonary congestion (eg, redistribution, alveolar or interstitial edema, or pleural effusions). 7) On optimal background therapy for ADHF (as determined by the investigator); subjects are required to have received, at a minimum, at least one hour of oxygen supplementation and at least one dose of IV furosemide at a minimum dose of 40 mg (or another diuretic at a comparable dose; eg, 2 mg bumetanide or 20 mg torsemide), with the last bolus being delivered >2 hours before study drug administration is initiated. 8) If subject received IV opiate, the last dose should have been >3 hours before administration of study drug. 9) If the subject is a woman of potential childbearing age, documentation of a negative urine pregnancy test result within 24 hours prior to randomization. 10) 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). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) Breathing rate 200 mmHg within an hour before randomization, or SBP <120 mmHg for subjects receiving intravenous (IV) inotropics or vasodilators. A SBP <90 mmHg any time before randomization. (Subjects on baseline IV inotropes or vasodilators must be on a stable dose for =3 hours prior to randomization.) 3) Brain natriuretic peptide (BNP) <400 pg/mL or NT pro-BNP <1200 pg/mL, anytime from initial presentation to hospital to randomization. 4) Active ongoing myocardial ischemia, hospitalization for acute myocardial infarction, or administration of thrombolytic therapy in the last 30 days. 5) Any cardiogenic shock (SBP <90 mmHg with signs or symptoms of organ hypoperfusion) from initial presentation to randomization. 6) Body temperature = 38ºC. 7) Acute unstable clinical condition such as a hemodynamically significant arrhythmia or a persistent heart rate =130 bpm or is refractory to treatment (at the time of screening), or any unstable heart failure syndrome requiring any mechanical-assist device or emergency surgery. 8) Acute decompensated heart failure associated with endocrine, metabolic, or drug-related toxicity. 9) Percutaneous coronary intervention, coronary artery bypass graft surgery, other cardiac surgery, or major noncardiac surgery within 90 days prior to randomization. 10) Any volume depletion or severe electrolyte imbalance. 11) Anemia (hemoglobin <10 mg/dL or hematocrit <30%). 12) Significant acute or chronic respiratory disorder (eg, severe chronic obstructive pulmonary disease) or primary pulmonary hypertension with baseline dyspnea that may interfere with the ability to interpret dyspnea assessments or hemodynamic measurements. 13) For subjects with concomitant invasive hemodynamic monitoring (ie, pulmonary artery catheter monitoring): Baseline PCWP of = 20 mmHg.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy and safety of ularitide with placebo in subjects hospitalized for symptomatic ADHF.;Secondary Objective: To characterize the pharmacokinetic (limited to steady-state concentration [Css] and clearance [CL]) and immunogenicity profiles of ularitide versus placebo in subjects hospitalized for symptomatic ADHF. To assess a subject’s change in quality of life throughout dosing and during follow up compared with baseline.;Primary end point(s): A statistically significant improvement in the mean scores of subject-assessed dyspnea, as measured by the 7 point Likert scale, and SGA, as measured by the 7 point Likert scale, at 6 hours from initiation of study drug infusion for the ularitide group compared with the placebo group. Additionally, a trend towards improvement in dyspnea at 3 hours and SGA at 3 and 48 hours from initiation of study drug infusion for the ularitide group compared with the placebo group will also be assessed. | — |
Countries
Finland, Lithuania
Outcome results
None listed