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

Primary Purpose

Heart Failure

Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
AZD9977
Spironolactone
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure focused on measuring Heart failure., Oral selective mineralocorticoid receptor modulator., Heart failure with preserved ejection fraction (HFpEF).

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Research Site
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Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Spironolactone

AZD9977

Arm Description

Spironolactone treatment for 28 days

AZD9977 treatment for 28 days

Outcomes

Primary Outcome Measures

Relative change (%) from baseline in serum potassium
To compare the effect of AZD9977 with spironolactone on serum potassium (sK+)

Secondary Outcome Measures

Plasma trough concentrations (Ctrough) values of spironolactone and AZD9977
To evaluate the pharmacokinetics (PK) of AZD9977 and spironolactone
Relative change (%) from baseline in serum potassium
To compare the effects of AZD9977 with spironolactone on serum potassium at Day 14.

Full Information

First Posted
September 21, 2018
Last Updated
April 30, 2020
Sponsor
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT03682497
Brief Title
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

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Terminated
Why Stopped
Attendance at study sites carries risk of COVID-19 infection. Non-attendance at planned study site visits has unacceptable study related patient safety risk.
Study Start Date
November 1, 2018 (Actual)
Primary Completion Date
March 31, 2020 (Actual)
Study Completion Date
March 31, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure
Keywords
Heart failure., Oral selective mineralocorticoid receptor modulator., Heart failure with preserved ejection fraction (HFpEF).

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
68 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Spironolactone
Arm Type
Active Comparator
Arm Description
Spironolactone treatment for 28 days
Arm Title
AZD9977
Arm Type
Experimental
Arm Description
AZD9977 treatment for 28 days
Intervention Type
Drug
Intervention Name(s)
AZD9977
Intervention Description
AZD9977 capsules taken orally for 28 days.
Intervention Type
Drug
Intervention Name(s)
Spironolactone
Intervention Description
Spironolactone tablets taken orally for 28 days.
Primary Outcome Measure Information:
Title
Relative change (%) from baseline in serum potassium
Description
To compare the effect of AZD9977 with spironolactone on serum potassium (sK+)
Time Frame
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 Outcome Measure Information:
Title
Plasma trough concentrations (Ctrough) values of spironolactone and AZD9977
Description
To evaluate the pharmacokinetics (PK) of AZD9977 and spironolactone
Time Frame
PK samples will be taken (within 60 min prior to dose) at day 1, 7, 14, 21 and 28.
Title
Relative change (%) from baseline in serum potassium
Description
To compare the effects of AZD9977 with spironolactone on serum potassium at Day 14.
Time Frame
Measurements on day 1, 7 and 14 will be used. The primary comparison between Spironolactone and AZD9977 will be done at day 14.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
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.
Facility Information:
Facility Name
Research Site
City
Plovdiv
ZIP/Postal Code
4002
Country
Bulgaria
Facility Name
Research Site
City
Sofia
ZIP/Postal Code
1309
Country
Bulgaria
Facility Name
Research Site
City
Sofia
ZIP/Postal Code
1784
Country
Bulgaria
Facility Name
Research Site
City
Brandys nad Labem
ZIP/Postal Code
250 01
Country
Czechia
Facility Name
Research Site
City
Ceska Lipa
ZIP/Postal Code
470 77
Country
Czechia
Facility Name
Research Site
City
Jaromer
ZIP/Postal Code
551 01
Country
Czechia
Facility Name
Research Site
City
Louny
ZIP/Postal Code
440 01
Country
Czechia
Facility Name
Research Site
City
Pardubice
ZIP/Postal Code
530 02
Country
Czechia
Facility Name
Research Site
City
Praha
ZIP/Postal Code
130 00
Country
Czechia
Facility Name
Research Site
City
Praha
ZIP/Postal Code
140 59
Country
Czechia
Facility Name
Research Site
City
Katowice
ZIP/Postal Code
40-081
Country
Poland
Facility Name
Research Site
City
Kraków
ZIP/Postal Code
31-202
Country
Poland
Facility Name
Research Site
City
Legnica
ZIP/Postal Code
59-220
Country
Poland
Facility Name
Research Site
City
Warszawa
ZIP/Postal Code
02-097
Country
Poland
Facility Name
Research Site
City
Wrocław
ZIP/Postal Code
50-981
Country
Poland
Facility Name
Research Site
City
Hull
ZIP/Postal Code
HU3 2JZ
Country
United Kingdom
Facility Name
Research Site
City
Leicester
ZIP/Postal Code
LE3 9PQ
Country
United Kingdom
Facility Name
Research Site
City
Sheffield
ZIP/Postal Code
S5 7AU
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD Sharing Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD Sharing Access Criteria
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD Sharing URL
https://astrazenecagroup-dt.pharmacm.com/DT/Home

Learn more about this trial

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

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