Evaluation of Safety and Efficacy of Sodium Zirconium Cyclosilicate in Pediatric Hyperkalemia: An Open-Label Study

The primary objective of this open-label study is to assess the ability to achieve and maintain **normokalaemia** in pediatric patients with **hyperkalaemia** during the Correction Phase (CP) and the 28-day Maintenance Phase (MP) when treated with different dose levels of **sodium zirconium cyclosilicate** (SZC). Achieving and maintaining normokalaemia is clinically significant as it helps prevent the adverse effects associated with elevated potassium levels, such as cardiac arrhythmias and muscle weakness.

Secondary objectives include:

• Evaluating the change in serum potassium (S-K+) levels in children treated with SZC.
• Assessing changes in serum aldosterone levels and serum electrolytes, including bicarbonate, as well as spot urinary pH and urinary electrolyte levels during the MP.
• Evaluating the ability to maintain normokalaemia in children during the Long-term Maintenance Phase (LTMP).

The clinical trial involves a total of **82 participants** diagnosed with **hyperkalaemia**. The study population includes both male and female subjects from birth to under 18 years of age. Participants are required to have either acute or chronic hyperkalaemia, with some receiving a stable peritoneal dialysis regimen for a minimum of two months. The trial population was selected based on specific inclusion criteria, including the ability to achieve and maintain normokalaemia with SZC treatment. Participants must be able to undergo repeated blood draws or effective venous catheterization. Females of childbearing potential are required to have a negative pregnancy test prior to the first dose and must use two forms of medically acceptable contraception if sexually active. The study includes a vulnerable population, as it involves children and adolescents. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the safety and efficacy of **sodium zirconium cyclosilicate** (SZC) in pediatric patients with **hyperkalaemia**. This study is structured as an open-label trial, focusing on both the correction and maintenance of normokalaemia in children. The trial is divided into two main phases: the Correction Phase (CP) and the 28-day Maintenance Phase (MP). The primary objective during the CP is to assess the ability to achieve normokalaemia with different dose levels of SZC, while the MP aims to evaluate the maintenance of normokalaemia in children who have achieved it during the CP.

Participants will be involved in the study for a maximum treatment period of 26 weeks. The trial includes several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor progress and safety, and an end-of-study visit to assess the final outcomes. The inclusion criteria require participants to be from birth to less than 18 years of age, with specific requirements for those on stable peritoneal dialysis. Exclusion criteria are not explicitly detailed in the provided data.

The study will terminate early for participants who do not achieve normokalaemia within the CP or if any safety concerns arise. The primary endpoints include achieving normokalaemia within three days during the CP and maintaining serum potassium levels within the normokalaemia range during the MP. Secondary endpoints involve monitoring serum potassium levels at each scheduled visit and changes in serum aldosterone and electrolytes during the MP.

Participants are expected to provide written informed consent, and females of childbearing potential must adhere to specific contraceptive measures. The trial is estimated to conclude by December 26, 2024, with recruitment having started on November 26, 2018. The study is not categorized as low intervention and is classified as a Phase 3 trial, focusing on the long-term treatment of hyperkalaemia in pediatric patients.

The clinical trial involves the administration of **sodium zirconium cyclosilicate** in two formulations. The first experimental medication is **AZD7270**, an oral suspension containing sodium zirconium cyclosilicate as the active substance. This formulation is designed for pediatric use and is administered orally. The maximum daily dose is 10 grams, with a total maximum dose of 10 grams over a treatment period of up to 26 weeks. The administration schedule is determined based on the specific needs of the pediatric patients with hyperkalemia, and compliance is monitored throughout the study.

The second formulation used in the trial is **Lokelma 5 g powder for oral suspension**, which also contains sodium zirconium cyclosilicate. This formulation is not specifically designed for pediatric use but is included in the study to evaluate its efficacy and safety in maintaining normokalemia. Similar to AZD7270, Lokelma is administered orally with a maximum daily dose of 10 grams and a total maximum dose of 10 grams over a 26-week period. The dosing schedule is consistent with the study protocol, and participant compliance is closely monitored.

Both formulations are provided by AstraZeneca AB and are classified as chemical substances. The trial does not include any non-experimental treatments such as placebo or comparator treatments. The primary objective of the trial is to assess the ability of these formulations to achieve and maintain normokalemia in pediatric patients with hyperkalemia. The study is conducted in an open-label manner, allowing for direct observation of the treatment effects and participant adherence to the dosing regimen.

The efficacy of the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoints include the achievement of **normokalaemia** within the Correction Phase (CP) within 3 days, and the maintenance of serum potassium (S-K+) levels within the normokalaemia range at each of the last two scheduled visits during the 28-day Maintenance Phase (MP). Secondary endpoints will evaluate the S-K+ level at each scheduled visit across all phases, changes in serum aldosterone levels from baseline to Week 3 of the MP, and changes in serum electrolytes, including bicarbonate, as well as spot urinary pH and urinary electrolytes from baseline to Week 3 of the MP. Additionally, in the Long-Term Maintenance Phase (LTMP), the S-K+ value within the normokalaemia range will be assessed at each scheduled visit.