Evaluation of Pharmacodynamic Effects, Safety, and Tolerability of Patiromer in Pediatric Patients with Hyperkalemia: A Phase 2, Open-Label, Multiple Dose Study

The primary objective of this study is to evaluate the change in **potassium** levels from baseline to Day 28 following the administration of different doses of **patiromer** in children aged 0 to less than 12 years with **hyperkalemia**. This is clinically relevant as managing potassium levels is crucial in preventing potential cardiac and muscular complications associated with hyperkalemia in pediatric patients.

Secondary objectives include assessing the safety and tolerability of patiromer in the same pediatric population. Understanding the safety profile and tolerability is essential for ensuring the therapeutic regimen is both effective and safe for long-term use in children.

The clinical trial involves a total of **26 participants** diagnosed with **hyperkalemia**. The study population consists of pediatric subjects under the age of 12, including both male and female participants. These individuals are considered a vulnerable population due to their age. Participants were selected based on their medical condition, with specific criteria ensuring that their potassium levels exceed the age-appropriate upper limit of normal. The trial includes children who are capable of receiving regular external feeding and medication, including via tubes. Lifestyle considerations such as diet and physical activity are not specified, but participants must be on stable doses of certain medications, if applicable, for at least 14 days prior to screening. The trial aims to assess changes in potassium levels following the administration of different doses of patiromer over a 28-day period.

The clinical trial is designed as a **Phase 2**, open-label, multicenter study to evaluate the pharmacodynamic effects, safety, and tolerability of **patiromer** in pediatric subjects under 12 years of age diagnosed with **hyperkalemia**. The trial consists of two parts: a 4-week pharmacodynamic/dose-ranging period and an optional 52-week safety extension period. The primary objective is to assess changes in potassium levels from baseline to Day 28 following administration of different doses of patiromer. Secondary endpoints include changes in potassium levels at various intervals, occurrence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), and changes in vital signs and laboratory safety evaluations.

Participants will be randomly assigned to receive either 1g or 2g of patiromer in powder form for oral suspension. The trial will commence with a screening visit to confirm eligibility, which includes pediatric subjects with hyperkalemia, who are able to receive regular external feeding and medication. The inclusion criteria require that subjects have potassium levels above the age-appropriate upper limit of normal, and they must be expected to require treatment for hyperkalemia for at least 28 days. The trial will exclude any subjects who do not meet these criteria.

The study visits are structured to include an initial screening visit, followed by regular follow-up visits on Day 3, Day 7, Day 14, and Day 28, with additional visits during the optional safety-extension period. The end-of-study visit will occur at the conclusion of the 4-week period or at the end of the safety extension if the participant continues. The expected length of participant involvement is a minimum of 28 days, with the possibility of extending to 56 weeks if the safety extension is pursued. Conditions that may lead to early termination from the study include non-compliance with the study protocol, withdrawal of consent, or any adverse events that, in the opinion of the investigator, warrant discontinuation of the study drug.

The clinical trial involves the administration of **Patiromer**, a polymer-based active substance, formulated as a **powder for oral suspension**. Two dosage forms are utilized in the study: Patiromer 1g and Patiromer 2g. Both formulations are designed for pediatric use and are provided by Vifor Pharma Inc. The medication is administered orally, with a maximum daily dose of 25 grams and a total maximum dose of 9800 grams over a treatment period of up to 56 days. The primary objective is to evaluate the pharmacodynamic effects, safety, and tolerability of Patiromer in children under 12 years of age with **hyperkalaemia**.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the trial. The study focuses solely on the administration of Patiromer to assess its impact on potassium levels from baseline to Day 28. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. The trial is conducted as an open-label, Phase 2 study, allowing for direct observation of the drug's effects in the target population.

Efficacy in this clinical trial will be assessed by evaluating changes in **potassium** levels from baseline to Day 28. The primary endpoint focuses on the reduction of potassium levels in children under 12 years of age with hyperkalaemia following administration of different doses of patiromer. Secondary endpoints include changes in potassium levels at additional timepoints: Day 3, Day 7, Day 14, and at the end of the study Part 1, as well as during the optional safety-extension period. The occurrence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) will also be monitored. Additional secondary endpoints involve changes in vital signs, 12-lead ECG, and clinical safety laboratory evaluations. Laboratory safety endpoints of special interest include the occurrence of blood potassium levels below the lower limit of normal (LLN) and above the upper limit of normal (ULN), as well as occurrences of blood magnesium, serum calcium, phosphate, fluoride, creatinine, bicarbonate, and blood urea nitrogen levels that are outside the normal range for the respective age. These efficacy parameters will be measured and collected using validated laboratory tests at specified timepoints throughout the study.