Evaluation of Glucothera Plus Solution for Peritoneal Dialysis in Pediatric End-Stage Kidney Disease: A Safety Assessment of Levocarnitine and Drug Combination

The primary objective of this study is to demonstrate the **safety** of Glucothera Plus in the pediatric population undergoing peritoneal dialysis for **End-stage Kidney Disease**. Establishing the safety profile of this solution is clinically significant as it ensures that the treatment does not pose undue risks to children, a vulnerable patient group, thereby supporting its use in managing this severe condition.

Secondary objectives include assessing efficacy parameters, specifically the restoration of **L-carnitine** levels. Evaluating these parameters is crucial for understanding the therapeutic benefits of Glucothera Plus beyond its safety, potentially improving clinical outcomes for pediatric patients with end-stage kidney disease.

The clinical trial focuses on a **pediatric population** diagnosed with **End-stage Kidney Disease** (ESRD). Participants include both male and female patients under the age of 18, who have been undergoing treatment with Continuous Ambulatory Peritoneal Dialysis (CAPD) or Automated Peritoneal Dialysis (APD) for at least six months. The study population is characterized by an L-carnitine plasma level of ≤30 nmol/ml and a dwell volume ranging from 800 ml/m² to 1200 ml/m² body surface. Participants have not experienced peritonitis episodes in the last three months and have provided written informed consent. The trial involves a vulnerable population, and the sponsor has not provided the total number of participants. The selection criteria ensure that the study population is homogenous in terms of treatment and health status, allowing for a focused assessment of the safety of Glucothera Plus in this specific demographic.

The clinical trial is designed to evaluate the safety of **Glucothera Plus**, a **solution for peritoneal dialysis**, in a pediatric population diagnosed with **end-stage kidney disease**. This is a Phase III, randomized, double-blind, controlled trial. The trial is expected to commence on April 1, 2024, and conclude by December 31, 2024. The study will involve multiple visits, including an initial screening visit, several follow-up visits, and an end-of-study visit. The inclusion criteria require participants to be male or female patients under 18 years old, diagnosed with end-stage renal disease, and undergoing continuous ambulatory peritoneal dialysis (CAPD) or automated peritoneal dialysis (APD) for at least six months. Participants must have a plasma **L-carnitine** level of ≤30 nmol/ml, a dwell volume between 800 ml/m² and 1200 ml/m² body surface, and no peritonitis episodes in the last three months. Written informed consent is mandatory for participation.

The trial will assess primary endpoints based on continuous adverse events reporting, including blood pressure and weight evaluation. Secondary endpoints will include Kt/V urea, 24-hour peritoneal ultrafiltration, 24-hour urinary volume, peritoneal equilibration test, residual kidney function, and plasma L-carnitine levels. Tolerability will be assessed through blood chemistry and hematology. The sequence of study visits is structured as follows: the initial screening visit (V1) will confirm eligibility and baseline measurements. Follow-up visits (V2 and V3) will monitor safety and efficacy parameters, while the final visit (V4) will conclude the study assessments. The expected duration of participant involvement is approximately four months, with a maximum treatment period of four weeks. Conditions that may lead to early termination from the study include the occurrence of significant adverse events or withdrawal of consent by the participant or their legal guardian.

The clinical trial involves the administration of **GLUCOTHERA PLUS**, a **solution for peritoneal dialysis**. This experimental medication is designed for **intraperitoneal use** and is intended to demonstrate safety in the pediatric population. The solution contains a combination of active substances, including **levocarnitine**, **magnesium chloride hexahydrate**, **sodium chloride**, **calcium chloride dihydrate**, **glucose monohydrate**, and **sodium lactate**. The maximum daily dose is set at 25% (V/V) percent volume/volume, with a total maximum dose of 25% (V/V) percent volume/volume over a treatment period of up to four weeks. The pharmaceutical form is specifically tailored for peritoneal dialysis, and the product is of chemical origin.

**Levocarnitine**, also known as L-carnitine, is a chemical substance included in the formulation to support metabolic processes. **Magnesium chloride hexahydrate** (E511) is incorporated to maintain electrolyte balance. **Sodium chloride**, commonly referred to as sodium chlorid, is used to ensure isotonicity of the solution. **Calcium chloride dihydrate**, or calcii chloridum dihydricum, is added to provide necessary calcium ions. **Glucose monohydrate**, also known as dextrose monohydrate, serves as an energy source. Lastly, **sodium lactate**, or lactic acid sodium salt, is included to help regulate the pH of the solution.

Throughout the trial, participant compliance with the dosing schedule will be closely monitored to ensure adherence to the treatment protocol. The study does not involve any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment. The trial is conducted under the sponsorship of IPERBOREAL PHARMA S.R.L., and the product is not classified as a pediatric formulation or an orphan drug. The trial's main objective is to establish the safety profile of GLUCOTHERA PLUS in children undergoing peritoneal dialysis.

Efficacy in the clinical trial of Glucothera Plus for peritoneal dialysis in children will be assessed using several secondary endpoints. These include the measurement of **Kt/V urea**, 24-hour peritoneal ultrafiltration, 24-hour urinary volume, and the Peritoneal Equilibration Test, all evaluated at timepoints V2 and V3. Additionally, residual kidney function will be assessed at the same timepoints. Plasma **L-carnitine** levels will be measured at V1, V2, and V3 to evaluate the treatment's impact on this biomarker. Tolerability will be assessed through blood chemistry and hematology at V2, V3, and V4. These parameters will be collected and analyzed to determine the efficacy of Glucothera Plus in the pediatric population undergoing peritoneal dialysis.