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

This is an interventional treatment trial for Heart Failure Read More

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