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

Phase 1

Terminated

• Conditions: Heart Failure
• Interventions: Drug: Spironolactone; Drug: AZD9977

• Registration Number: NCT03682497
• Lead Sponsor: AstraZeneca

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-09-21
• Study First Submitted QC: 2018-09-21
• Study First Posted: 2018-09-24
• Study Start: 2018-11-01
• Primary Completion: 2020-03-31
• Study Completion: 2020-03-31
• Status Verified: 2020-04
• Last Update Submitted: 2020-04-30
• Last Update Posted: 2020-05-01

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 68

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Spironolactone	Spironolactone	Spironolactone treatment for 28 days
AZD9977	AZD9977	AZD9977 treatment for 28 days

Primary Outcome Measures

Name	Time	Method
Relative change (%) from baseline in serum potassium	Measurements on day 1, 7, 14, 21 and 28 will be used. The primary comparison between Spironolactone and AZD9977 will be done at day 28.	To compare the effect of AZD9977 with spironolactone on serum potassium (sK+)

Secondary Outcome Measures

Name	Time	Method
Plasma trough concentrations (Ctrough) values of spironolactone and AZD9977	PK samples will be taken (within 60 min prior to dose) at day 1, 7, 14, 21 and 28.	To evaluate the pharmacokinetics (PK) of AZD9977 and spironolactone
Relative change (%) from baseline in serum potassium	Measurements on day 1, 7 and 14 will be used. The primary comparison between Spironolactone and AZD9977 will be done at day 14.	To compare the effects of AZD9977 with spironolactone on serum potassium at Day 14.

Trial Locations

Locations (1)

Research Site; 🇬🇧 Sheffield, United Kingdom