Clinical trial NCT02350725 (phase 1/phase 2, status: completed)
Conditions: heart failure
ICD codes: I50.814, I09.81, I50.82, I50.89, I50.9, T86.22, I11.0
Drugs: furosemide injection solution for subcutaneous administration (80 mg), oral furosemide tablets (80 mg)
SMILES: CCOC(=O)OC[C@H]1O[C@@H](OC2=NN(C(C)C)C(C)=C2CC2=CC=C(OC(C)C)C=C2)[C@H](O)[C@@H](O)[C@@H]1O, NS(=O)(=O)C1=C(Cl)C=C(NCC2=CC=CO2)C(=C1)C(O)=O
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