Clinical Trials Register

Summary
EudraCT Number:	2018-000175-33
Sponsor's Protocol Code Number:	D9484C00001
National Competent Authority:	Slovakia - SIDC (Slovak)
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2019-08-02
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Slovakia - SIDC (Slovak)

A.2

EudraCT number

2018-000175-33

A.3

Full title of the trial

A Phase II, Randomised, Double-Blind, Placebo Controlled, Parallel-Group, Multicentre, Three Month Duration Potassium Reduction Initiative to Optimize RAAS Inhibition Therapy with Sodium Zirconium Cyclosilicate in Heart Failure (PRIORITIZE HF)

Randomizované, dvojito-zaslepené, placebom kontrolované, paralelné, multicentrické klinické skúšanie vo fáze II, ktorého cieľom je znížiť hladinu draslíka pre optimalizáciu liečby inhibítorom RAAS počas 3 mesiacov liečby hydrát sodno-zirkoničitou soľou kyseliny kremičitej u pacientov so srdcovým zlyhávaním (PRIORITIZE HF).

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A three months study evaluating if the potassium binder sodium zirconium cyclosilicate can help manage a common side effect of heart failure treatment, and thereby allow heart failure treatment to be improved

Klinické skúšanie, ktorého cieľom je zhodnotiť, či užívanie lieku na zníženie hladiny draslíka (hydrát sodno-zirkoničitej soli kyseliny kremičitej) počas 3 mesiacov pomôže zvládať časté vedľajšie účinky liečby na srdcové zlyhávanie, a tým zlepšiť liečbu na srdcové zlyhávanie.

A.3.2

Name or abbreviated title of the trial where available

PRIORITIZE HF

A.4.1

Sponsor's protocol code number

D9484C00001

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03532009

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	AstraZeneca AB
B.1.3.4	Country	Sweden
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	AstraZeneca AB
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AstraZeneca AB
B.5.2	Functional name of contact point	Information Center
B.5.3	Address:
B.5.3.1	Street Address	Karlebyhus, Astaallen
B.5.3.2	Town/ city	Södertälje
B.5.3.3	Post code	151 85
B.5.3.4	Country	Sweden
B.5.4	Telephone number	18772409479
B.5.6	E-mail	information.center@astrazeneca.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Lokelma
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca AB
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Sodium zirconium cyclosilicate OS
D.3.2	Product code	AZD7270
D.3.4	Pharmaceutical form	Powder for oral suspension
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Sodium zirconium cyclosilicate
D.3.9.1	CAS number	242800-27-7
D.3.10	Strength
D.3.10.1	Concentration unit	g gram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Powder for oral suspension
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Heart Failure;
Hyperkalaemia

E.1.1.1

Medical condition in easily understood language

Heart failure (HF) occurrs when the heart is unable to pump sufficient blood to maintain the needs of the body. Hyperkalaemia occurs when the level of potassium in the circulating blood is too high.

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10008908
E.1.2	Term	Chronic heart failure
E.1.2	System Organ Class	100000004849

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To determine if there is a difference between sodium zirconium cyclosilicate (ZS) and placebo in RAAS (renin angiotensin aldosterone system) blockade treatment.

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
2. Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses.
3. Provision of signed and dated written genetic informed consent prior to collection of sample for genetic analysis. Individuals refusing to provide informed consent for genetic testing may still be included in the study, but will not have to provide samples for genetic analysis.
4. Subject must be ≥18 years of age inclusive, at the time of signing the informed consent form.
5. Individuals with established documented diagnosis of symptomatic heart failure with reduced ejection fraction (HFrEF).
6. Individuals with left ventricular ejection fraction ≤ 40%.
7. Individuals receiving background standard of care (an ACEi, ARB, or ARNI with or without low-dose MRA) for HFrEF and treated according tolocally recognized guidelines with both drugs and devices, as appropriate.
8. Individuals with mild hyperkalaemia or at risk of developing hyperkalaemia during the study.
9. Women of childbearing potential must have a negative pregnancy test during screening (before first dose of investigational product [IP]) performed locally.

E.4

Principal exclusion criteria

1. HF due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis,hypertrophic (obstructive) cardiomyopathy or uncorrected primary valvular disease.
2. Current acute decompensated HF, hospitalization due to decompensated HF within 4 weeks prior to enrolment, or myocardial infarction (MI), unstable angina, stroke or transient ischemic attack (TIA) within 12 weeks prior to enrolment.
3. Coronary revascularization or valvular repair/replacement within 12 weeks prior to enrolment or planned to undergo any of these operations after randomization.
4. Implantation of a Cardiac Resynchronization Therapy (CRT) device or Implantable Cardioverter Defibrillator (ICD) within 12 weeks prior to enrolment or intent to perform atrial fibrillation ablation or to implant a CRT device.
5. Previous cardiac transplantation or implantation of a ventricular assistance device (VAD) or similar device, or transplantation or implantation expected after randomization.
6. Symptomatic bradycardia or second (Mobitz type 2) or third-degree heart block without a pacemaker.
7. Symptomatic hypotension or systolic blood pressure (BP) <95 mmHg on 2 consecutive measurements.
8. Receiving dialysis or anticipated by the investigator to require dialysis therapy within 3 months.
9. Prior history of hypersensitivity to a renin angiotensin aldosterone system inhibitor (RAASi) drug, including but not limited to development of angioedema, icterus, hepatitis, or neutropenia or thrombocytopenia requiring treatment modification.
10. Addison’s disease or other causes of hypoaldosteronism.
11. Known hypersensitivity to sodium zirconium cyclosilicate.
12. Any condition outside the cardiovascular (CV) and renal disease area, such as but not limited to malignancy, with a life expectancy of less than 2 years based on investigator´s clinical judgement.
13. Active malignancy requiring treatment.
14. MRA therapies that are mainly investigational and/or are not widely available as an oral dosing formulation (eg, canrenoate and finerenone) are excluded.
15. Treated with potassium binding resins such as sodium polystyrene sulfonate (SPS; e.g. Kayexalate®) or calcium polystyrene sulfonate (CPS; e.g. Resonium®) or the cation exchange polymer, patiromer sorbitex calcium (Veltassa®) within 7 days prior to the first dose of study drug.
16. Treated with potassium supplements within 7 days prior to randomization.
17. Participation in another clinical study with ZS at any time or treatment with any investigational product (IP) during the last 3 months.
18. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff, AstraZeneca representatives, and/or staff at the study site).
19. Judgment by the investigator that the subject should not participate in the study if the subject is unlikely to comply with study procedures, restrictions and requirements.
20. Previous randomisation in the present study.
21. Subjects with a family history of long QT syndrome, presence of cardiac arrhythmias or conduction defects that require immediate treatment, or a QTc(corrected QT interval) of ≥550 msec.

E.5 End points

E.5.1

Primary end point(s)

Proportion of subjects in the following categories at 3 months:
- No ACEi/ARB/ARNI or at less than target dose and no MRA
- ACEi/ARB/ARNI at target dose and no MRA
- MRA at less than target dose
- MRA at target dose

E.5.1.1

Timepoint(s) of evaluation of this end point

Approximately at 3 months

E.5.2

Secondary end point(s)

N/A

E.5.2.1

Timepoint(s) of evaluation of this end point

N/A

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Brazil

Bulgaria

Canada

Hungary

Poland

Romania

Russian Federation

Slovakia

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

140

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

140

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

120

F.4.2

For a multinational trial

F.4.2.1

In the EEA

126

F.4.2.2

In the whole clinical trial

280

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-09-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-09-17

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2020-05-22

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials