Clinical Trials Register

Summary
EudraCT Number:	2021-003527-14
Sponsor's Protocol Code Number:	D9480C00023
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-11-17
Trial 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

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A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2021-003527-14

A.3

Full title of the trial

An Open-Label, Randomised, Phase 4 Study of Continuing Sodium Zirconium Cyclosilicate (SZC) after Discharge in Participants with Chronic Kidney Disease treated for Hyperkalaemia

A.3.1

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

Continuing Sodium Zirconium Cyclosilicate (SZC) after discharge study

A.3.2

Name or abbreviated title of the trial where available

CONTINUITY

A.4.1

Sponsor's protocol code number

D9480C00023

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
B.5.2	Functional name of contact point	Clinical Study Information Center
B.5.3	Address:
B.5.3.1	Street Address	1800 Concord Pike
B.5.3.2	Town/ city	Wilmington DE
B.5.3.3	Post code	19803
B.5.3.4	Country	United States
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
D.3.2	Product code	SZC
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.3.9.2	Current sponsor code	Sodium zirconium cyclosilicate
D.3.9.3	Other descriptive name	SODIUM ZIRCONIUM CYCLOSILICATE (SZC)
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients with Chronic Kidney Disease treated for Hyperkalaemia whilst in hospital, who are normokalemic and established on maintenance dose of SZC at discharge.

E.1.1.1

Medical condition in easily understood language

Hyperkalemia means that the potassium level in the blood is higher than normal

E.1.1.2

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10020646
E.1.2	Term	Hyperkalaemia
E.1.2	System Organ Class	10027433 - Metabolism and nutrition disorders

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 evaluate the efficacy of continuing SZC as part of the discharge medications, compared to SoC, in maintaining NK

E.2.2

Secondary objectives of the trial

To evaluate the effect of continuing SZC as part of the discharge
medications, compared to SoC:
1. in reducing the incidence of the composite outcome of all-cause hospital admissions or ED visits with HK as a contributing factor, or all cause
death, or use of rescue-therapy for HK
2. in reducing the incidence of all-cause hospital admissions or ED visits with HK as a contributing factor
3. in reducing the number of all-cause hospital admissions or ED visits with HK as a contributing factor
4. in reducing the incidence of hospital admissions or ED visits with HK as a contributing factor
5. in reducing the number of hospital admissions or ED visits with HK as a contributing factor
6. on reducing the risk of RAASi down-titration or discontinuation

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1 Must be 18 years of age or older, at the time of signing the informed consent
2 Admitted to hospital (inpatient care; directly or from ED)
3 With:
- diagnosed CKD (any stage)
or
- eGFR < 90 ml/min/1.73 m2 at, or within 3 months of, study screening, based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (Levey et al, 2009). Note: Race/ethnicity should not be included in CKD-EPI equation calculation.
4 Local laboratory K+ measurement within 24 hours of baseline visit (visit 2), where result is either:
• Hyperkalaemic as defined by site's local practice and K+ ≤ 6.5 mmol/L
• Or, normokalaemic: K+ between ≥ 3.> 5.0 and ≤ 5.0 mmol/L, where patient started and is receiving treatment for this episode of HK
5 Male or female
6 Capable and willing of giving signed informed consent as described in Appendix A which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.

E.4

Principal exclusion criteria

1 Hospitalisation for an acute cardiovascular event within 12 weeks prior
to screening
2 Unable to take oral SZC drug mix
3 -
4 With a life expectancy of less than 6 months
5 Any medical condition that, in the opinion of the investigator or sponsor makes the participant not suitable for inclusion
6 QT interval corrected by the Fridericia method (QTcF) > 550 msec
7 History of QT prolongation associated with other medications that required discontinuation of that medication
8 Congenital long QT syndrome
9 Clinically significant arrythmias as judged by the investigator
10 Ongoing treatment with SZC or patiromer before current ED visit/hospital admission (ongoing treatment with other K-binders before current ED visit/hospital admission is allowed).
Note: Initiation of SZC or patiromer during the current ED
visit/hospitalisation preceding enrolment is allowed.
11 Chronic haemodialysis or peritoneal dialysis or the recipient of or scheduled date for a kidney transplant. Note: Emergency/unscheduled haemodialysis to treat HK during the current ED visit/hospitalisation preceding enrolment is allowed.
12 Participation in another clinical study with an investigational medical product (IMP) administered during the month before screening.
13 Known hypersensitivity to SZC or any of the excipients of the product
14 Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
15 Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements
16 Previous randomisation in the present study
17 For women only: Women of child-bearing potential (WOCBP; ie, those who are not chemically or surgically sterilised or who are not
postmenopausal) who are not willing to use one of the methods of contraception described hereafter, or who are not stable on the
contraception method for the last one month, from the time of signing the informed consent throughout the study and 7 days after the last
dose
(a) Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, transdermal
(b) Progestogen-only hormonal contraception associated with inhibition
of ovulation: oral, injectable, implantable
(c) Intrauterine device
(d) Intrauterine hormone-releasing system
(e) Bilateral tubal occlusion
(f) Vasectomised partner (vasectomised partner is a highly effective birth control method provided that partner is the sole sexual partner of
the WOCBP participant and that the vasectomised partner has received medical assessment of the surgical success
(g) Sexual abstinence: it is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire
period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant.
18 For WOCBP only: Women who have a positive pregnancy test at screening OR women who are breastfeeding.

E.5 End points

E.5.1

Primary end point(s)

Occurrence (yes/no) of NK (K+ between 3.5 and 5.0 mmol/L, inclusive) at 180 days post-discharge.

E.5.1.1

Timepoint(s) of evaluation of this end point

Up to 180 days post-discharge

E.5.2

Secondary end point(s)

- Time to first occurrence of:
• All-cause hospital admissions, or ED visits with HK as a contributing
factor, or all-cause death or use of rescue therapy for HK at any time
post -discharge up to 180 days.
• All-cause hospital admission, or ED visit, with HK as a contributing
factor at any time post -discharge up to 180 days.
• Number of all-cause hospital admission, or ED visits, with HK as a
contributing factor at any time post discharge up to 180 days.
• Hospital admission or ED visit, both with HK as a contributing factor at
any time post-discharge up to 180 days.
• Number of hospital admission or ED visits, both with HK as a
contributing factor at any time post discharge up to 180 days.
• RAASi down titration (or discontinuation)

E.5.2.1

Timepoint(s) of evaluation of this end point

At any time post-discharge up to 180 days.

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

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)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Local standard of care

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

United Kingdom

Belgium

France

Italy

Netherlands

Spain

E.8.7

Trial has a data monitoring committee

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

337

F.4.2.2

In the whole clinical trial

344

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)

No intervention will follow the end of the study. Decision to continue on SZC treatment or SoC will be at investigator's discretion.

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

2021-11-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-08-12

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2024-10-12

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