Clinical trial NCT02350725: Furosemide Pharmacodynamics and Pharmacokinetics After Subcutaneous or Oral Administration
Official title: A Single Center, Randomized, Open-label, Cross-over Exploratory Study to Evaluate the Pharmacodynamic and Pharmacokinetic Response to a Subcutaneous Administration or Oral Administration of Furosemide in Subjects With Heart Failure Presenting With Chronic Fluid Overload
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Heart Failure
Keywords: Chronic Fluid Overload
Lead sponsor: scPharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2015-01-30
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this pilot study is to investigate the pharmacodynamic and pharmacokinetic parameters of a novel furosemide formulation administered subcutaneously as compared to oral furosemide.


Eligibility criteria: Inclusion Criteria:

* Written informed consent obtained before any assessment is performed
* Male and female subjects ≥18 years of age, with body weight \<120 kg and body mass index (BMI) \<30 kg/m2
* Female subjects must be at least 2 years post-menopausal
* Participant must have been on oral furosemide (40 mg oid or bid) or therapeutic equivalent (bumetanide 1 mg oid or bid) for a period 90 days before the first dose of study medication
* History of chronic heart failure according to 2012 ESC guidelines with presence of moderate symptoms of chronic fluid overload. Chronic fluid overload is defined as presence of stable signs and symptoms of heart failure and congestion, like dyspnea at mild exertion or minimal exertion, pulmonary congestion and/or peripheral edema at the time of presentation in combination with elevated levels on natriuretic peptides (NT-proBNP \> 300 ng/L)
* In the opinion of the investigator, able to participate in the study

Exclusion Criteria:

* Acute Decompensated Heart Failure (ADHF) or recent history of ADHF or significant worsening in their HF symptoms (within prior 2 weeks)
* Contraindication to furosemide
* Systolic BP (SBP) \< 90 mm Hg
* Temperature \> 38°C (oral or equivalent) or sepsis or active infection requiring i.v. anti-microbial treatment
* Serum sodium \< 130 mmol/L and Serum potassium \< 3.0 mmol/L
* Current or planned (throughout the completion of study drug infusion) treatment with any i.v. therapies, including inotropic agents, vasopressors, levosimendan, nesiritide or analogues; or mechanical support (intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, or any ventricular assist device)
* History of gastric or intestinal surgery that may affect absorption of oral medication
* Presence or need for urinary catheterization
* Current or planned ultrafiltration, hemofiltration, or dialysis
* Impaired renal function defined as an estimated glomerular filtration rate (eGFR) on admission \< 30 mL/min/1.73 m2 will be calculated as per standard at local laboratory
* Administration of intravenous radiographic contrast agent within 72 hours prior to screening or acute contrast-induced nephropathy at the time of screening
* Major surgery within 30 days prior to screening
* Administration of an investigational drug or implantation of investigational device, or participation in another trial, within 30 days before screening
* Inability to follow instructions or comply with procedures
* Any surgical or medical condition which in the opinion of the investigator may interfere with participation in the study or which may affect the outcome of the study

Primary outcomes:
measure: Diuresis and natriuresis
timeFrame: 8 hours
Secondary outcomes:
measure: Body Water Content
timeFrame: 8 hours
measure: Pharmacokinetic profiles
timeFrame: 8 hours
measure: Cardiac Markers (NTpro-BNP, hs-Trop T, galectin-3)
timeFrame: 8 hours
measure: Dypsnea Scores on Visual Analog Scale and Likert Scale
timeFrame: 8 hours
measure: Injection site reaction on Draize Scale and Visual Analog Pain Scale
timeFrame: 8 hours
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
affiliation: University Medical Center Groningen
name: Rudolf A. de Boer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: