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

• Status: Terminated
• Trial end date: 2020-03-31
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: AstraZeneca
• Treatments: Spironolactone

Criteria

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.