Clinical trial NCT03682497: Study in HFpEF Patients to Compare the Effect of AZD9977 and Spironolactone on Serum Potassium
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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Heart Failure
Keywords: Heart failure.
Oral selective mineralocorticoid receptor modulator.
Heart failure with preserved ejection fraction (HFpEF).
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2018-09-24
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Relative change (%) from baseline in serum potassium
timeFrame: 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 outcomes:
measure: Plasma trough concentrations (Ctrough) values of spironolactone and AZD9977
timeFrame: PK samples will be taken (within 60 min prior to dose) at day 1, 7, 14, 21 and 28.
measure: Relative change (%) from baseline in serum potassium
timeFrame: Measurements on day 1, 7 and 14 will be used. The primary comparison between Spironolactone and AZD9977 will be done at day 14.
Other outcomes:
Locations:
city: Plovdiv
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Brandys nad Labem
country: Czechia
facility: Research Site
city: Ceska Lipa
country: Czechia
facility: Research Site
city: Jaromer
country: Czechia
facility: Research Site
city: Louny
country: Czechia
facility: Research Site
city: Pardubice
country: Czechia
facility: Research Site
city: Praha
country: Czechia
facility: Research Site
city: Praha
country: Czechia
facility: Research Site
city: Katowice
country: Poland
facility: Research Site
city: Kraków
country: Poland
facility: Research Site
city: Legnica
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Wrocław
country: Poland
facility: Research Site
city: Hull
country: United Kingdom
facility: Research Site
city: Leicester
country: United Kingdom
facility: Research Site
city: Sheffield
country: United Kingdom
facility: Research Site
Study officials:
References: