Evaluation of Pharmacokinetics, Safety, and Efficacy of Empagliflozin in Pediatric Patients with Chronic Kidney Disease: A Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of this study is to evaluate the pharmacokinetics, safety, and efficacy of oral empagliflozin in paediatric patients aged 2 to 17 years diagnosed with chronic kidney disease at risk of progression.

This clinical trial involves 70 participants diagnosed with chronic kidney disease. The study population consists of both male and female pediatric patients between the ages of 2 and 17 years. Participants are selected based on the presence of kidney disease of any underlying etiology, characterized by an estimated glomerular filtration rate (eGFR) between 20 and <90 mL/min/1.73 m² and a urinary albumin-to-creatinine ratio (UACR) of ≥300 mg/g. Eligible individuals must be on a stable dose of maximally tolerated standard of care therapy for at least 30 days prior to screening. This therapy is expected to include a renin-angiotensin-aldosterone system (RAAS) inhibitor, such as an angiotensin receptor blocker (ARB) or an angiotensin-converting enzyme inhibitor (ACEi). Stability in dosage must be maintained throughout the placebo-controlled portion of the study. For patients requiring daily immunosuppressive therapy due to immunological causes, a stable regimen is also mandatory.

This randomised, double-blind, placebo-controlled trial includes an open-label extension to evaluate the pharmacokinetics, safety, and efficacy of empagliflozin in paediatric patients aged 2 to 17 years with chronic kidney disease. The study methodology involves a screening visit to assess eligibility based on estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) levels. Following screening, participants receive either empagliflozin or a matching placebo. The primary endpoints include changes in UACR and urine glucose from Day 1 to the Week 24 visit. Secondary objectives involve monitoring changes in eGFR, urine protein-to-creatinine ratio (UPCR), and plasma concentrations of the active substance. The clinical course includes periodic follow-up visits and an end-of-treatment period. Participation in the trial is contingent upon maintaining a stable dose of standard of care therapy, such as angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and stable immunosuppressive therapy if applicable. Potential adverse events or serious adverse events are monitored throughout the study duration.

The experimental treatment consists of empagliflozin administered as a 10 mg film-coated tablet. The medication is intended for oral administration.

The control group receives a placebo designed to match the appearance of the empagliflozin film-coated tablets.

The assessment of efficacy in patients with chronic kidney disease involves the evaluation of several primary and secondary endpoints. The primary efficacy parameters consist of the change from Day 1 to the Week 24 visit in the urinary albumin-to-creatinine ratio (UACR) and the change in urine glucose concentration from Day 1 to the Week 24 visit.

Secondary efficacy evaluations include:

• Change in estimated glomerular filtration rate (eGFR) over the course of treatment with empagliflozin.
• The annual rate of change in eGFR from Week 8 to Week 24, incorporating treatment effect extrapolation from adult data.
• Change from Day 1 to the Week 24 visit in the urine protein-to-creatinine ratio (UPCR).