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

Heart Failure Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03682497
• Other study ID #: D6401C00004
• Status: Terminated
• Phase: Phase 1
• Start date: November 1, 2018
• Est. completion date: March 31, 2020

Study information

• Verified date: April 2020
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 68
• Est. completion date: March 31, 2020
• Est. primary completion date: March 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Heart Failure

Intervention

Drug:
• AZD9977
AZD9977 capsules taken orally for 28 days.
• Spironolactone
Spironolactone tablets taken orally for 28 days.

Locations

Country	Name	City	State
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Czechia	Research Site	Brandys nad Labem
Czechia	Research Site	Ceska Lipa
Czechia	Research Site	Jaromer
Czechia	Research Site	Louny
Czechia	Research Site	Pardubice
Czechia	Research Site	Praha
Czechia	Research Site	Praha
Poland	Research Site	Katowice
Poland	Research Site	Kraków
Poland	Research Site	Legnica
Poland	Research Site	Warszawa
Poland	Research Site	Wroclaw
United Kingdom	Research Site	Hull
United Kingdom	Research Site	Leicester
United Kingdom	Research Site	Sheffield

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

Bulgaria,  Czechia,  Poland,  United Kingdom, 

Outcome

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