NCT03682497

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.

Trial Health

60
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
68

participants targeted

Target at P75+ for phase_1 heart-failure

Timeline
Completed

Started Nov 2018

Geographic Reach
4 countries

18 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 21, 2018

Completed
3 days until next milestone

First Posted

Study publicly available on registry

September 24, 2018

Completed
1 month until next milestone

Study Start

First participant enrolled

November 1, 2018

Completed
1.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 31, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 31, 2020

Completed
Last Updated

May 1, 2020

Status Verified

April 1, 2020

Enrollment Period

1.4 years

First QC Date

September 21, 2018

Last Update Submit

April 30, 2020

Conditions

Heart Failure

Keywords

Heart failure.Oral selective mineralocorticoid receptor modulator.Heart failure with preserved ejection fraction (HFpEF).

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (2)

  • 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.

  • 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.

Study Arms (2)

Spironolactone

ACTIVE COMPARATOR

Spironolactone treatment for 28 days

Drug: Spironolactone

AZD9977

EXPERIMENTAL

AZD9977 treatment for 28 days

Drug: AZD9977

Interventions

AZD9977DRUG

AZD9977 capsules taken orally for 28 days.

AZD9977
SpironolactoneDRUG

Spironolactone tablets taken orally for 28 days.

Spironolactone

Eligibility Criteria

Age18 Years - 99 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (18)

Research Site

Plovdiv, 4002, Bulgaria

Location

Research Site

Sofia, 1309, Bulgaria

Location

Research Site

Sofia, 1784, Bulgaria

Location

Research Site

Brandýs nad Labem, 250 01, Czechia

Location

Research Site

Česká Lípa, 470 77, Czechia

Location

Research Site

Jaroměř, 551 01, Czechia

Location

Research Site

Louny, 440 01, Czechia

Location

Research Site

Pardubice, 530 02, Czechia

Location

Research Site

Prague, 130 00, Czechia

Location

Research Site

Prague, 140 59, Czechia

Location

Research Site

Katowice, 40-081, Poland

Location

Research Site

Krakow, 31-202, Poland

Location

Research Site

Legnica, 59-220, Poland

Location

Research Site

Warsaw, 02-097, Poland

Location

Research Site

Wroclaw, 50-981, Poland

Location

Research Site

Hull, HU3 2JZ, United Kingdom

Location

Research Site

Leicester, LE3 9PQ, United Kingdom

Location

Research Site

Sheffield, S5 7AU, United Kingdom

Location

MeSH Terms

Conditions

Heart Failure

Interventions

AZD9977Spironolactone

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

LactonesOrganic ChemicalsPregnenesPregnanesSteroidsFused-Ring CompoundsPolycyclic Compounds

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 21, 2018

First Posted

September 24, 2018

Study Start

November 1, 2018

Primary Completion

March 31, 2020

Study Completion

March 31, 2020

Last Updated

May 1, 2020

Record last verified: 2020-04

Data Sharing

IPD Sharing
Will share

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.

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.
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.
More information

Locations

PL(5)BU(3)GB(3)CZ(7)