Study in HFpEF Patients to Compare the Effect of AZD9977 and Spironolactone on Serum Potassium

A Phase I, Open Label, Randomized, Parallel Group, Multicentre Study to Compare the Effect of AZD9977 and Spironolactone on Serum Potassium [sK+] During 28 Days in Patients With HFmrEF or HFpEF and eGFR in the Range of ≥40 and ≤70 mL/Min/1.73m2.

This is a Phase I, Multicentre study to Compare the Effect of AZD9977 and Spironolactone on Serum Potassium [sK+] during 28 days in Patients with HFmrEF or HFpEF and eGFR in the range of ≥40 and ≤70 mL/min/1.73m2.

Inclusion Criteria:

• Symptoms and signs consistent with a diagnosis of heart failure (HF)
• Left ventricular ejection fraction (LVEF) ≥40% by transthoracic echocardiography within the past 12 months
• Plasma NT-proBNP level ≥125 pg/ml (≥ 600pg/mL if patient has persistent or permanent atrial fibrillation, atrial flutter, or atrial tachycardia)
• Estimated glomerular filtration rate (eGFR) ≥40 and ≤70ml/min/1.73m2 (by CKD-EPI formula).
• Baseline serum potassium (sK+) level ≥3.5 and ≤4.8mmol/l.
• Stable doses of the following medications at baseline for at least 4 weeks prior to randomisation:

Angiotensin receptor blocker (ARB) or Angiotensin converting enzyme inhibitor (ACEi) Loop diuretic (up to a 120mg furosemide dose or equivalent

Exclusion Criteria:

• Patients with documented LVEF <40% at any time (i.e. patients with previously impaired LVEF that has now improved are not permitted).
• Patients experiencing acute decompensation of heart failure requiring hospital admission or escalation in therapy.
• Primary cardiomyopathy (e.g. constrictive, restrictive, infiltrative, toxic, hypertrophic, congenital or any primary cardiomyopathy in judgment of Investigator).
• Hyponatraemia, defined as serum Na+ <135 mmol/L at the time of enrollment.
• Persistent resting sinus tachycardia >110 bpm or sinus bradycardia <45bpm.
• Systolic blood pressure (BP) <110mmHg or >180mmHg.
• Diastolic BP <60 mmHg or >100 mmHg.
• Patients previously intolerant to MRA (e.g. spironolactone or eplerenone) for any reason.
• Medical conditions associated with development of hyperkalaemia (e.g. Addison's disease).
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥2.0 times the upper limit of normal (ULN).
• Patients who have been taking an MR antagonist within 1 month prior to randomization.