Phase I Interaction Study of Istaroxime and Digoxin in Subjects With Stable Heart Failure

Inclusion Criteria:

Main screening inclusion criteria :

• Signed informed consent;
• Male or female patients ≥18 years;
• Female patients of childbearing potential must not be pregnant;
• Chronic stable cardiac function impairment (no change in heart failure medication over the last 3 months and without any dosage adjustment in the last 4 weeks);
• Systolic blood pressure (SBP) of ≥ 90 mmHg and ≤ 140 mmHg;
• LVEF ≤ 35% by any method (to be performed at screening if not measured within the last 12 months);
• Chronic treatment (i.e. once daily dosing without interruption) with oral digoxin started at least 3 months prior to study entry and without any concomitant administration of other positive inotropic drugs;

Exclusion Criteria:

Main screening exclusion criteria :

• Need for current or intermittent intravenous positive inotrope administration within the preceding 6 months, or hemodynamic support devices;
• Acute coronary syndrome within the past 3 months;
• Coronary artery bypass graft or percutaneous coronary intervention within the past 3 months;
• Stroke within the past 6 months;
• Atrial fibrillation or uncontrolled heart rate (HR) (> 100 beats per minute [bpm]);
• Significant arrhythmia or second or third degree atrio-ventricular block;
• Valvular disease as the primary cause of HF;
• Significant ECG abnormalities as assessed by appropriately qualified physician or investigator including QTcF >450;
• Positive testing for Human Immunodeficiency Virus (HIV), Hepatitis B and/or Hepatitis C;

Main randomization exclusion criteria:

• HR > 100 bpm or < 50 bpm;
• Serum potassium > 5.3 mmol/L or < 3.8 mmol/L and magnesium > 1.1 mmol/L or < 0.6 mmol/L,
• TN I > ULN.