A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled Study to Evaluate the Renal Hemodynamic Effects of RLX030 and Placebo Infused for 24 Hours in Subjects With Chronic Heart Failure (CHF)

Novartis Pharmaceuticals1 site in 1 country118 target enrollmentFebruary 2012

ConditionsChronic Heart Failure (CHF)

InterventionsRLX030 Placebo

DrugsRLX030 Placebo

Overview

Phase: Phase 2
Intervention: RLX030
Conditions: Chronic Heart Failure (CHF)
Sponsor: Novartis Pharmaceuticals
Enrollment: 118
Locations: 1
Primary Endpoint: Change from baseline in glomerular filtration rate (GFR) as measured by Iothalamate (IOTH) clearance in subjects with CHF after 24 hours i.v. infusion of RLX030
Status: Completed
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This study will assess the renal hemodynamic effect of RLX030 infusion in subjects with chronic heart failure. In addition safety and effects on renal function and biomarkers will be assessed.

Registry

clinicaltrials.gov

Start Date

February 2012

End Date

December 2012

Last Updated

5 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Novartis Pharmaceuticals

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Written informed consent must be obtained before any assessment is performed.
•Male and female heart failure patients with body weight \<160 kg, on standard therapy including a stable dose of furosemide 40-240 mg/day orally (p.o). or equivalent dose of loop diuretics, reduced systolic function (LVEF ≤ 45% measured within the past 6 months), BNP ≥ 100 pg/mL or NT-pro-BNP of ≥ 400 pg/mLNYHA Class II or III, and worsening symptoms, e.g. fatigue, dyspnea, breathlessness within 3 months
•Mild to moderate renal impairment
•Exclusion criteria:
•Systolic blood pressure (SBP) \< 110 mm Hg at the time of randomization
•Administration of intravenous radiographic contrast agent within 72 hours prior to randomization or acute contrast-induced nephropathy at the time of randomization
•Current use of non-steroidal antiinflammatory drugs (NSAIDs)
•Current or planned (through the completion of study drug infusion) treatment with any i.v. therapies, including vasodilators (including nesiritide), positive inotropic agents, vasopressors, levosimendan, or mechanical support (intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, or any ventricular assist device).
•Clinically significant hepatic impairment defined as hepatic encephalopathy of any degree or total bilirubin \> 50 μmol/l (3 mg/dl) or, if patient is not on warfarin therapy, INR \> 2.0 (or Prothrombin Time \> 2 \* ULN)
•Other protocol-defined inclusion/exclusion criteria may apply.

Exclusion Criteria

Not provided

Arms & Interventions

RLX030

RLX030 as intravenous infusion for 24 hours.

Intervention: RLX030

Placebo

Placebo as intravenous infusion for 24 hours.

Intervention: Placebo

Outcomes

Primary Outcomes

Change from baseline in glomerular filtration rate (GFR) as measured by Iothalamate (IOTH) clearance in subjects with CHF after 24 hours i.v. infusion of RLX030

Time Frame: Baseline, during and after the end of 24 hours infusion

Serial blood and urine collections over time for determination of IOTH and its clearance respectively

Change from baseline in renal plasma flow (RPF) measured by Para-aminohippuric acid (PAH) clearance in subjects with CHF after 24 hours intravenous (i.v) infusion of RLX030

Time Frame: Baseline, during and after the end of 24 hours infusion

Serial blood and urine collections over time for determination of PAH and its clearance respectively

Secondary Outcomes

Change from baseline in filtration fraction (FF) in subjects with CHF after 24 hours infusion of RLX030(Baseline, during and after the end of 24 hours of infusion)
Change over time in Diuresis(During 24 hours of infusion and after the end of the infusion)
Change over time in calculated creatinine clearance(During 24 hours of infusion and after the end of the infusion)
Change over time on fractional sodium excretion(natriuresis)(During 24 hours of infusion and after the end of the infusion)
Central aortic systolic pressure-time curve(During 24 hours of infusion and after the end of the infusion)
Radial augmentation index-time curve(During 24 hours of infusion and after the end of the infusion)
Number of patients with adverse events, serious adverse events and death(During 24 hours of infusion and after the end of the infusion)
Pharmacokinetics of RLX030: area under the serum concentration-time curve from time zero to infinity (AUCinf)Time(During 24 hours of infusion and for 24 hours after the end of infusion)
Pharmacokinetics of RLX030: area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)(During 24 hours of infusion and for 24 hours after the end of infusion)
Pharmacokinetics of RLX030: serum concentration over 20 hours of infusion (C24h)(During 24 hours of infusion and for 24 hours after the end of infusion)
Pharmacokinetics of RLX030: terminal elimination half-life (T1/2)following intravenous administration(During 24 hours of infusion and for 24 hours after the end of infusion)
Pharmacokinetics of RLX030: mean residence time (MRT)intravenous administration(During 24 hours of infusion and for 24 hours after the end of infusion)
Pharmacokinetics of RLX030: volume of distribution at steady state (Vss) following intravenous administration(During 24 hours of infusion and for 24 hours after the end of infusion)
Pharmacokinetics of RLX030: systemic clearance from serum (CL) following intravenous administration(natriuresis)(During 24 hours of infusion and for 24 hours after the end of infusion)
Corrected QT (QTc) Interval Using Fridericia's and Bazett's Formula(Baseline, during the 24 hours of infusion and after the end of the infusion)