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

Sponsor
AstraZeneca (Industry)
Overall Status
Terminated
CT.gov ID
NCT03682497
Collaborator
(none)
68
Enrollment
18
Locations
2
Arms
17
Actual Duration (Months)
3.8
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
68 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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.
Actual Study Start Date :
Nov 1, 2018
Actual Primary Completion Date :
Mar 31, 2020
Actual Study Completion Date :
Mar 31, 2020

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Spironolactone

Spironolactone treatment for 28 days

Drug: Spironolactone
Spironolactone tablets taken orally for 28 days.
Experimental: AZD9977

AZD9977 treatment for 28 days

Drug: AZD9977
AZD9977 capsules taken orally for 28 days.

Outcome Measures

Primary Outcome Measures

  1. 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

  1. 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

  2. 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 99 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Research Site Plovdiv Bulgaria 4002
2 Research Site Sofia Bulgaria 1309
3 Research Site Sofia Bulgaria 1784
4 Research Site Brandys nad Labem Czechia 250 01
5 Research Site Ceska Lipa Czechia 470 77
6 Research Site Jaromer Czechia 551 01
7 Research Site Louny Czechia 440 01
8 Research Site Pardubice Czechia 530 02
9 Research Site Praha Czechia 130 00
10 Research Site Praha Czechia 140 59
11 Research Site Katowice Poland 40-081
12 Research Site Kraków Poland 31-202
13 Research Site Legnica Poland 59-220
14 Research Site Warszawa Poland 02-097
15 Research Site Wrocław Poland 50-981
16 Research Site Hull United Kingdom HU3 2JZ
17 Research Site Leicester United Kingdom LE3 9PQ
18 Research Site Sheffield United Kingdom S5 7AU

Sponsors and Collaborators

  • AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT03682497
Other Study ID Numbers:
  • D6401C00004
First Posted:
Sep 24, 2018
Last Update Posted:
May 1, 2020
Last Verified:
Apr 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by AstraZeneca
Heart failure.
Oral selective mineralocorticoid receptor modulator.
Heart failure with preserved ejection fraction (HFpEF).
Additional relevant MeSH terms:
Heart Failure
Spironolactone

Study Results

No Results Posted as of May 1, 2020