Clinical trial NCT02329834 (phase 2/phase 3, status: completed)
Conditions: heart failure
ICD codes: I50.814, I09.81, I50.82, I50.89, I50.9, T86.22, I11.0
Drugs: fursemide injection solution for subcutaneous administration (80 mg), furosemide injection, usp
SMILES: NS(=O)(=O)C1=C(Cl)C=C(NCC2=CC=CO2)C(=C1)C(O)=O
Eligibility criteria:

        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