Study to Evaluate the Effects of Oral Administration of Lixivaptan in Patients With Congestive Heart Failure

Inclusion Criteria:

• Ability to understand the purpose and risks of the study and to provide signed and dated informed consent.
• Men and women aged 18 years or older.
• History of chronic CHF defined as requiring standard HF treatment (including diuretics) for a minimum of 30 days.
• Documented LVEF by any method within 12 months prior to screening.

• The patient has clinical evidence of volume overload at the time of inclusion with at least one of the following:

  • Dyspnea
  • Pulmonary congestion (rales)
  • Peripheral edema
  • Increased jugular venous pressure and/or hepatic congestion with ascites
  • Chest x-ray consistent with CHF
  • Plasma brain natriuretic peptide (BNP) ≥150 pg/mL or N-terminal prohormone brain natriuretic peptide (NT pro-BNP) ≥450 pg/mL

Exclusion Criteria:

• Women who are pregnant (positive pregnancy test), breastfeeding, or who will not adhere to the reproductive precautions as outlined in this protocol and in the informed consent form (ICF).
• Sustained (three blood pressure measurements over 1 hour) systolic blood pressure <90 mmHg at Screening or Day 0.
• ST segment elevation myocardial infarction or stroke within 30 days prior to Screening.
• Hemodynamically destabilizing cardiac arrhythmia within 30 days prior to Day 0.
• Clinically significant valvular disease.
• Known clinically significant obstructive, restrictive, or hypertrophic cardiomyopathy.
• Cardiac surgery or percutaneous coronary intervention within 30 days prior to Day 0.
• Major surgical procedure within 7 days prior to Day 0.
• Likely to undergo cardiac transplantation, left ventricular assist device (LVAD) or other device implantation, or other cardiac surgery within 3 months after Screening.
• Placement of implantable cardioverter defibrillator or cardiac resynchronization therapy device within 60 days prior to Day 0.
• CHF due to uncorrected thyroid disease, active myocarditis, or known amyloid cardiomyopathy.
• Presence of any clinically significant (as determined by the Investigator) endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, oncologic, and/or other major disease that might interfere with safe and compliant participation in this study.

• Screening laboratory findings as follows:

  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 times the upper limit of normal
  • Total bilirubin >2.0 mg/dL
  • Serum creatinine >3.0 mg/dL
  • Hemoglobin <9.0 g/dL
• Uncontrolled diabetes mellitus as defined by the Investigator (e.g., glycosylated hemoglobin [HbA1c] >9%).
• History of chronic drug/medication abuse within the past 6 months; or current alcohol abuse.
• Co-morbid condition with an expected survival of less than 3 months.
• Known allergy to any vasopressin antagonist or any condition for which treatment with a vasopressin antagonist may present undue risk to the patient.
• Current or recent administration (within 7 days of Day 0) of prohibited medications as listed in Section 8.6.4 .
• Participation in any other investigational study of drugs or devices within 30 days prior to Screening.