Crossover Study to Compare the Pharmacokinetics and Bioavailability of a Novel Furosemide Regimen Administered Subcutaneously vs. the Same Dose Administered Intravenously in Subjects With Chronic Heart Failure

Inclusion Criteria:

An Institutional Review Board (IRB) approved informed consent is signed and dated prior to any study-related activities.
Male and female subjects ≥18 years of age, with body volume and weight <130 kg and body mass index (BMI) <38 kg/m2
Females will be non-pregnant, non-lactating, and post-menopausal, surgically sterile (e.g., tubal ligation, hysterectomy), or use TWO (2) of the following forms of contraception: IUD, IUD with spermicide, female condom with spermicide, contraceptive sponge with spermicide, an intravaginal system, diaphragm with spermicide, cervical cap with spermicide, a male sexual partner who agrees to use a male condom with spermicide, a sterile sexual partner, OR abstinence
History of at least 3 months treated heart failure (NYHA class II/III) with presence of symptoms of chronic volume overload requiring ongoing treatment with oral furosemide at a dose of ≥ 40 mg per day for at least 30 days prior to baseline
NT-proBNP > 300 pg/mL or BNP > 100 pg/mL
Agrees to abstain from using alcohol, caffeine-containing products, and tobacco-/nicotine-containing products through CRU discharge (period 2).
Able to participate in the study in the opinion of the investigator
Has the ability to understand the requirements of the study and is willing to comply with all study procedures

Exclusion Criteria:

Acute Decompensated Heart Failure (ADHF) or recent history of hospitalization for heart failure in the last 4 weeks
Worsening of signs or symptoms of heart failure in the two weeks prior to the Screening, or those expected to require intravenous loop diuretics or in-patient treatment for heart failure during the study
Systolic BP (SBP) < 90 mm Hg
Temperature > 38°C (oral or equivalent) or sepsis or active infection requiring IV anti-microbial treatment
Serum sodium < 130 mEq/L and Serum potassium < 3.0 mEq/L
Significant other cardiac abnormalities which may interfere with study participation or study assessments
Current or planned treatment during the study with any IV 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)
Diagnosed with Type I diabetes mellitus or Type II diabetes requiring insulin therapy
Presence or need for urinary catheterization, urinary tract abnormality, or disorder interfering with urination
Impaired renal function, defined as an estimated glomerular filtration rate (eGFR) on admission < 45 mL/min/1.73m2, calculated using the simplified Modification of Diet in Renal Disease (sMDRD) equation
Indication of moderate-to-severe hepatic dysfunctions as determined by the investigator
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 interventional trial, within 30 days prior to Screening
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
Positive test for hepatitis B, hepatitis C, or HIV at Screening
Positive urine drug screen at Screening or Baseline
Concomitant use of any drugs known to interact with furosemide
History of alcohol abuse within 6 months prior to screening, as determined by the Investigator
Positive alcohol breath test on admission to the CRU
History of severe allergic or hypersensitivity reactions to furosemide
Donation of greater than 100 mL of either whole blood or plasma within 30 days prior to study drug administration