SZC for Hyperkalemia
(PEDZ-K Trial)
Recruiting in Palo Alto (17 mi)
+43 other locations
Age: < 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: AstraZeneca
Must not be taking: Lactulose, Rifaximin, CPS, others
Disqualifiers: HIV, Cardiac arrhythmias, Haemodialysis, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Approved in 2 jurisdictions
Trial Summary
What is the purpose of this trial?Sodium zirconium cyclosilicate has been shown to be effective and safe in adults for the treatment of hyperkalaemia, and therefore it is expected to be beneficial in children. This study will evaluate the efficacy, safety and tolerability of sodium zirconium cyclosilicate for the treatment of hyperkalaemia in children \<18 years of age. Approximately 140 participants will enter CP at approximately 46 sites in locations including but not limited to Europe and North America for this study. Treatment will include 3 phases: the CP, MP, and LTMP. Enrolment will start in 2 cohorts, ages 6 to \< 12 years and 12 to \< 18 years. After review of accumulated data, the independent Data Monitoring Committee (iDMC) will recommend whether to open enrolment in the ages 2 to \< 6 years cohort and later in the ages 0 to \< 2 years cohort. All eligible participants with hyperkalaemia will enter an open-label Correction Phase (CP) receiving a fixed dose of SZC three times daily (TID) for up to 3 days until normokalaemia is achieved. Within each age cohorts 2 to \< 18 years, initial participants will be allocated to the dose level (DL) based on body weight equivalent to an adult 5 g TID. After recommendation of higher DLs by the iDMC, subsequent participants may be allocated in the CP to on body weight equivalent to an adult 10 g TID and then potentially on body weight equivalent to an adult 15 g TID. All participants in the ages 0 to \< 2 years cohort will be assigned to the same DL which will be decided based on data from older age cohorts. Participants who successfully achieve normokalaemia in the CP will enter a 28-day open-label Maintenance Phase (MP), which will be initiated with once daily administration of the dose received TID in the CP. During MP, the Investigator is able to titrate the dose up or down in the range 2.5 g to 15 g body weight equivalent to maintain normokalaemia. For participants who, at the end of MP, are normokalaemic or hyperkalaemic without being on maximum dose, the MP is followed by the option to continue the study in a long term maintenance phase (LTMP) where the same titration regimen is used as in MP.
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.
What data supports the effectiveness of the drug Sodium Zirconium Cyclosilicate (SZC) for treating hyperkalemia?
Sodium Zirconium Cyclosilicate (SZC) is a new drug used to treat hyperkalemia (high potassium levels in the blood) and is noted for having fewer side effects compared to older treatments. It is specifically designed to bind potassium, helping to lower its levels in the body.
12345Is Sodium Zirconium Cyclosilicate (SZC) safe for humans?
Sodium Zirconium Cyclosilicate (SZC) is generally considered safe for treating high potassium levels, with fewer side effects compared to older treatments. However, it can appear on imaging tests like CT scans and DXA, which might affect the results of these tests.
12346What makes the drug Sodium Zirconium Cyclosilicate (SZC) unique for treating hyperkalemia?
Sodium Zirconium Cyclosilicate (SZC) is a novel drug for treating hyperkalemia (high potassium levels) that works by specifically binding to potassium in the gut, which helps to remove excess potassium from the body. It is known for having fewer side effects compared to older treatments and is also radiopaque, meaning it can appear on imaging tests like CT scans.
12346Eligibility Criteria
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.
+7 more
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.
+19 more
Trial Timeline
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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Active Arm ( Sodium Zirconium Cyclosilicate SZC)Experimental Treatment5 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Research SiteVancouver, Canada
Research SiteMontreal, Canada
Research SiteStony Brook, NY
Research SiteNew York, NY
More Trial Locations
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Who Is Running the Clinical Trial?
AstraZenecaLead Sponsor
References
Clinical Implications of Sodium Zirconium Cyclosilicate Therapy in Patients with Systolic Heart Failure and Hyperkalemia. [2021]Sodium zirconium cyclosilicate (SZC), a newly introduced specific potassium binder, is introduced to treat hyperkalemia. However, the implications of SZC in up-titrating renin-angiotensin-aldosterone system inhibitors in patients with systolic heart failure remain unknown.
Radiopacity of sodium zirconium cyclosilicate on CT imaging. [2022]A patient who post-operatively develops hyperkalemia is treated with sodium zirconium cyclosilicate (Lokelma®), a novel agent used for the treatment of non-life-threatening hyperkalemia with reduced side effects as compared with its predecessors. On CT imaging of the chest, abdomen, and pelvis, a radiopaque fluid is noticed despite the patient not having received any oral or intravenous contrast nor any medications or supplements that may appear radiopaque. Based on previous CT imaging of zirconium-based tooth implants and their radiopaque appearance on images, it is hypothesized that the sodium zirconium cyclosilicate that the patient was administered is the explanation of the radiopacity on CT imaging. We performed an in-vitro experiment to confirm that Lokelma is radiopaque to support our hypothesis. It is important to fully understand the differential of what may cause different appearances on imaging as well as to eliminate potential sources of artifact prior to imaging, or alternatively, to potentially be able to use medications with known radiopaque properties as alternatives to contrast agents.
Correction to: Sodium Zirconium Cyclosilicate: A Review in Hyperkalaemia. [2019]The article Sodium Zirconium Cyclosilicate: A Review in Hyperkalaemia, written by Sheridan M. Hoy, was originally published Online First without open access.
A Newly Recognized DXA Confounder: The Potassium-Binding Medication Sodium Zirconium Cyclosilicate. [2021]Radio-dense artifacts, including contrast material, alter dual-energy X-ray absorptiometry (DXA) results. An apparent diffuse artifact was identified during spine DXA acquisition in a patient without recent radiographic procedures. The patient reported taking sodium zirconium cyclosilicate (SZC; Lokelma®) 10 g 1 h before scanning. SZC is a potassium-binding agent recently marketed to treat hyperkalemia. Given the chemical composition, we hypothesized that SZC may alter DXA results. This study evaluated if SZC affects DXA results using an encapsulated spine and a total body phantom.
Modified tricalcium silicate cement formulations with added zirconium oxide. [2018]Label="OBJECTIVES" NlmCategory="OBJECTIVE">This study aims to investigate the effect of modifying tricalcium silicate (TCS) cements on three key properties by adding ZrO2.
Experimental Calcium Silicate-Based Cement with and without Zirconium Oxide Modulates Fibroblasts Viability. [2017]The aim of this study was to verify whether the use of zirconium oxide as a radiopacifier of an experimental calcium silicate-based cement (WPCZO) leads to cytotoxicity. Fibroblasts were treated with different concentrations (10 mg/mL, 1 mg/mL, and 0.1 mg/mL) of the cements diluted in Dulbecco's modified Eagle's medium (DMEM) for periods of 12, 24, and 48 h. Groups tested were white Portland cement (WPC), white Portland cement with zirconium oxide (WPCZO), and white mineral trioxide aggregate Angelus (MTA). Control group cells were not treated. The cytotoxicity was evaluated through mitochondrial-activity (MTT) and cell-density (crystal violet) assays. All cements showed low cytotoxicity. In general, at the concentration of 10 mg/mL there was an increase in viability of those groups treated with WPC and WPCZO when compared to the control group (p