Renal Hemodynamic Effects of RLX030A in Subjects With Chronic Heart Failure (CHF)

Phase 2

Completed

Conditions: Chronic Heart Failure (CHF)

Interventions: Drug: RLX030
Drug: Placebo

Registration Number: NCT01546532

Lead Sponsor: Novartis Pharmaceuticals

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 118

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
RLX030	RLX030	RLX030 as intravenous infusion for 24 hours.
Placebo	Placebo	Placebo as intravenous infusion for 24 hours.

Primary Outcome Measures

Name	Time	Method
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	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	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 Outcome Measures

Name	Time	Method
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	The filtration fraction (FF) is derived as the ratio of GFR divided by RBF in percent.
Change over time in Diuresis	During 24 hours of infusion and after the end of the infusion	Urine samples will be collected for analyses.
Change over time in calculated creatinine clearance	During 24 hours of infusion and after the end of the infusion	Urine samples will be collected for analyses.
Change over time on fractional sodium excretion(natriuresis)	During 24 hours of infusion and after the end of the infusion	Urine samples will be collected for analyses.
Central aortic systolic pressure-time curve	During 24 hours of infusion and after the end of the infusion	A cuff will be used for a brachial blood pressure measurement and a wrist sensor for arterial pulse waveforms
Radial augmentation index-time curve	During 24 hours of infusion and after the end of the infusion	A cuff will be used for a brachial blood pressure measurement and a wrist sensor for arterial pulse waveforms
Number of patients with adverse events, serious adverse events and death	During 24 hours of infusion and after the end of the infusion	Monitoring of adverse events, serious adverse events and death from screening to end of study
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	Blood will be collected from an indwelling catheter.
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	Blood will be collected from an indwelling catheter.
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	Blood will be collected from an indwelling catheter.
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	Blood will be collected from an indwelling catheter.
Pharmacokinetics of RLX030: mean residence time (MRT)intravenous administration	During 24 hours of infusion and for 24 hours after the end of infusion	Blood will be collected from an indwelling catheter.
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	Blood will be collected from an indwelling catheter.
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	Blood will be collected from an indwelling catheter.
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	Continuous 12 lead Holter ECG monitoring for extraction of ECGs and analysis