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

AstraZeneca

Status and phase

Terminated

Phase 1

Conditions

Heart Failure

Treatments

Drug: AZD9977

Drug: Spironolactone

Study type

Interventional

Funder types

Industry

Identifiers

NCT03682497

D6401C00004

Details and patient eligibility

About

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.

Enrollment

68 patients

Sex

All

Ages

18 to 99 years old

Volunteers

No Healthy Volunteers

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.