SZC for Hyperkalemia

(PEDZ-K Trial)

Recruiting at 50 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: Lactulose, Rifaximin, CPS, others

Disqualifiers: HIV, Cardiac arrhythmias, Haemodialysis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

140 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of sodium zirconium cyclosilicate (SZC) for children with hyperkalemia, a condition characterized by excessive potassium in the blood. The study will evaluate how well this treatment reduces potassium levels in children across different age groups. Children requiring ongoing or short-term treatment for hyperkalemia, including those on stable dialysis, may be suitable candidates for this trial. Participants will receive the medication in phases to determine the optimal dose for maintaining normal potassium levels. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment for hyperkalemia in children.

Will I have to stop taking my current medications?

The trial requires that participants stop taking certain medications like lactulose, rifaximin, sodium polystyrene sulfonate, or patiromer before starting the study treatment. If you are on these medications, you will need to stop them for a specified period before joining the trial.

Is there any evidence suggesting that sodium zirconium cyclosilicate is likely to be safe for children?

Research has shown that sodium zirconium cyclosilicate (SZC) is generally safe for adults with high potassium levels in the blood. In studies involving 1,760 patients, SZC demonstrated a safety profile similar to a placebo, meaning it did not cause more side effects than a sugar pill. Importantly, no reports indicated dangerously low potassium levels, which supports its safety.

The FDA has already approved SZC for treating high potassium in adults, indicating its safety for this group. However, researchers are still studying its safety and effectiveness in children. So far, no major safety issues have emerged in adults, which is a positive sign for its potential use in children as well. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hyperkalemia?

Unlike the standard of care for hyperkalemia, which often includes treatments like diuretics and calcium polystyrene sulfonate, Sodium Zirconium Cyclosilicate (SZC) offers a unique approach. SZC is distinct because it acts by selectively binding potassium in the gastrointestinal tract, which helps rapidly reduce high potassium levels in the blood. This mechanism is different from other treatments that can have slower onset times or broader effects. Additionally, SZC can be administered conveniently as a powder mixed with water or sprinkled onto food, making it a flexible option for patients of all ages, including very young children. Researchers are excited about SZC because it promises a faster, targeted response to hyperkalemia with potentially fewer side effects.

What evidence suggests that sodium zirconium cyclosilicate is effective for hyperkalemia in children?

Research has shown that sodium zirconium cyclosilicate (SZC), the treatment under study in this trial, effectively treats hyperkalemia, a condition characterized by excessive potassium in the blood. Studies have found that patients taking SZC experienced a noticeable drop in potassium levels compared to those who did not take it. Lowering potassium levels helps prevent serious heart issues. SZC also aids individuals with heart failure, making it easier to manage their condition. The treatment is considered safe and effective for controlling potassium levels, offering a promising option for those with hyperkalemia. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for children under 18 with high blood potassium (hyperkalemia) who need long-term treatment. They must be able to have regular blood tests, not have severe gut issues or major surgeries, and can't be on certain medications or dialysis. Girls who can have babies must use two birth control methods.

Inclusion Criteria

I am under 18 years old.

My potassium levels are normal or high but I'm not on the highest dose of medication for it.

My heart's electrical activity, measured by an ECG, is within the normal range.

Exclusion Criteria

I might have a condition that reduces blood flow to my intestines.

You have false high levels of potassium in your blood due to certain health conditions.

My family has a history of long QT syndrome.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Correction Phase (CP)

Participants receive a fixed dose of SZC three times daily for up to 3 days until normokalaemia is achieved

Up to 3 days

Maintenance Phase (MP)

Participants who achieve normokalaemia in the CP enter a 28-day open-label Maintenance Phase with dose titration to maintain normokalaemia

28 days

Long-term Maintenance Phase (LTMP)

Participants may continue in a long-term maintenance phase with the same titration regimen as in MP

Up to 22 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Sodium Zirconium Cyclosilicate (SZC)

Trial Overview

The study tests different doses of Sodium Zirconium Cyclosilicate (SZC) in kids with hyperkalemia. It has three phases: correction, maintenance, and long-term maintenance where the dose may change to keep potassium levels normal.

How Is the Trial Designed?

Group I: Active Arm ( Sodium Zirconium Cyclosilicate SZC) Experimental Treatment 5 Interventions

Dosage formulation: 5 g sachets 2.5 g sachets 0.25 g sprinkle capsules 0.125 g sprinkle capsules (can be manufactured to support participants \<2 years of age) Route of administration: Oral Dosing instructions: SZC is provided as a powder. At the time of dosing SZC is mixed with a quantity of water or sprinkled onto semi-solid food (eg, milk, baby food, yogurt, or ice cream) within an hour of drug administration. Packaging and labelling: Study treatment will be provided in sachets packed in cartons or sprinkle capsules in high density polyethylene bottles, as appropriate for the dose. Each carton of sachets, individual sachets, and bottle of capsules will be labelled in accordance with Good Manufacturing Practice Annex 13 and per country regulatory requirement. Participant-specific dosing cards (diary) will be provided.

Sodium Zirconium Cyclosilicate (SZC) is already approved in European Union, United States for the following indications:

Approved in European Union as Lokelma for:

• Hyperkalemia

Approved in United States as Lokelma for:

• Hyperkalemia

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

Sodium zirconium cyclosilicate (Lokelma®) is effective in treating non-life-threatening hyperkalemia and has fewer side effects compared to older treatments.

The study suggests that Lokelma can appear radiopaque on CT imaging, which could help in differentiating it from other potential sources of radiopacity, thus providing a new perspective on imaging techniques in patients treated with this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiopacity of sodium zirconium cyclosilicate on CT imaging. Kolesnik, M., Berezovsky, D., Sayegh, M., et al.[2022]

The study tested a new dental material made of calcium silicate-based cement with zirconium oxide and found it to have low cytotoxicity, making it a promising option for root-end filling in dental procedures.

At a concentration of 10 mg/mL, both the white Portland cement and the zirconium oxide variant increased the viability of fibroblasts compared to the control group, suggesting potential benefits in dental applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental Calcium Silicate-Based Cement with and without Zirconium Oxide Modulates Fibroblasts Viability. Slompo, C., Peres-Buzalaf, C., Gasque, KC., et al.[2017]

Adding zirconium dioxide (ZrO2) to tricalcium silicate (TCS) cements does not affect their mechanical strength, maintaining similar fracture toughness to Biodentine, a control cement.

The modified TCS cements showed improved calcium release over time and reduced cytotoxicity, particularly the TCS 50 formulation, indicating it could be a safer and more effective option for dental applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified tricalcium silicate cement formulations with added zirconium oxide. Li, X., Yoshihara, K., De Munck, J., et al.[2018]

In a study of 24 patients with heart failure and hyperkalemia, sodium zirconium cyclosilicate (SZC) was safely administered for 3 months without causing adverse effects, including hypokalemia.

SZC therapy led to decreased serum potassium levels and allowed for increased doses of renin-angiotensin-aldosterone system inhibitors, which improved heart function as indicated by enhanced left ventricular ejection fraction and reduced plasma B-type natriuretic peptide levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Implications of Sodium Zirconium Cyclosilicate Therapy in Patients with Systolic Heart Failure and Hyperkalemia. Imamura, T., Oshima, A., Narang, N., et al.[2021]

Sodium zirconium cyclosilicate (SZC) significantly alters dual-energy X-ray absorptiometry (DXA) results, increasing bone mineral density (BMD) measurements by 18% to 110% in spine phantoms, indicating it may confound results in actual patients.

The study demonstrated a dose-dependent effect of SZC on body composition, with higher doses leading to significant increases in lean mass and decreases in fat mass, suggesting that DXA technologists should be cautious when interpreting results in patients taking SZC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Newly Recognized DXA Confounder: The Potassium-Binding Medication Sodium Zirconium Cyclosilicate. McCarney, B., Binkley, N., Krueger, D.[2021]

The article reviews the use of Sodium Zirconium Cyclosilicate as a treatment for hyperkalaemia, a condition characterized by elevated potassium levels in the blood.

Sodium Zirconium Cyclosilicate is effective in lowering potassium levels, providing a safe and efficient option for managing hyperkalaemia in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correction to: Sodium Zirconium Cyclosilicate: A Review in Hyperkalaemia. Hoy, SM.[2019]

Citations

1.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa1411487

Sodium Zirconium Cyclosilicate in Hyperkalemia

Patients with hyperkalemia who received ZS-9, as compared with those who received placebo, had a significant reduction in potassium levels at 48 ...

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/25415807/

Sodium zirconium cyclosilicate in hyperkalemia

Patients with hyperkalemia who received ZS-9, as compared with those who received placebo, had a significant reduction in potassium levels ...

3.

journals.lww.com

journals.lww.com/cjasn/fulltext/2019/06000/sodium_zirconium_cyclosilicate_among_individuals.7.aspx

Sodium Zirconium Cyclosilicate among Individuals with...

Individuals with severe hyperkalemia (K +>6.0 mmol/L) are at increased risk of cardiac arrhythmias and sudden death, and they often require emergency treatment ...

4.

jacc.org

jacc.org/doi/10.1016/j.jacc.2024.11.014

Sodium Zirconium Cyclosilicate for Management of ...

In participants with symptomatic HFrEF and hyperkalemia, SZC led to large improvements in optimizing the use and dose of MRA and K+ levels, and reductions in ...

5.

academic.oup.com

academic.oup.com/ckj/article/17/11/sfae313/7829284

Sodium zirconium cyclosilicate treatment and rates of ...

Sodium zirconium cyclosilicate (SZC) reduces serum potassium in patients with chronic hyperkalaemia in clinical trials, but its role in the ...

6.

lokelma-hcp.com

lokelma-hcp.com/explore-lokelma/safety

LOKELMA Safety Information | LOKELMA for Oral Suspension

LOKELMA is indicated for the treatment of hyperkalemia in adults. LOKELMA should not be used as an emergency treatment for life-threatening hyperkalemia.

7.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2018/207078s000lbl.pdf

LOKELMA is sodium zirconium - accessdata.fda.gov

The total exposure to LOKELMA in the safety and efficacy clinical trials of patients with hyperkalemia was 1,760 patients with 652 patients exposed to LOKELMA ...

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7771984/

Long-term safety and efficacy of sodium zirconium ...

Sodium zirconium cyclosilicate (SZC; formerly ZS-9) is a selective potassium (K + ) binder for the treatment of adults with hyperkalaemia.

9.

mayoclinic.org

mayoclinic.org/drugs-supplements/sodium-zirconium-cyclosilicate-oral-route/description/drg-20443787

Sodium zirconium cyclosilicate (oral route) - Side effects & ...

Sodium zirconium cyclosilicate is used to treat hyperkalemia (high potassium in the blood). ... Safety and efficacy have not been established.