Pharmacokinetic Evaluation of Oral Viscous Budesonide in Paediatric Patients with Eosinophilic Oesophagitis in Repaired Oesophageal Atresia.

Eosinophilic oesophagitis is a long-term complication of oesophageal atresia (EA), an uncommon condition that affects approximately 1 in 3500 infants. An exploratory, open-label phase 2 clinical trial was conducted in paediatric eosinophilic oesophagitis after oesophageal atresia (EoE-EA) to assess the safety, pharmacokinetics, and efficacy of oral viscous budesonide (OVB). In total, eight patients were enrolled in the study and assigned to a twice-daily dosing regimen of either 0.8 or 1 mg OVB, depending on age and height, administered for 12 weeks. OVB was safe and effective in the treatment of EoE-EA. The current investigation focuses on the pharmacokinetics of budesonide and the impact of an oral viscous formulation on its absorption and bioavailability. Using a non-linear mixed effects approach, two distinct absorption profiles were identified, despite marked interindividual variability in drug concentrations. Budesonide exposure was higher than previously reported in children following oral inhalation. Even though no significant effect has been observed on serum cortisol levels, future studies should consider exploring different doses, schedules, and/or treatment durations, as there may be an opportunity to reduce the risk of cortisol suppression.

Oral Viscous Budesonide in Children With Eosinophilic Esophagitis After Repaired Esophageal Atresia: A Clinical Trial.

OBJECTIVES: A high prevalence of eosinophilic esophagitis (EoE) has been reported in children with repaired esophageal atresia (EA). Topical steroids proved to be an effective and safe therapy in EoE, although not approved in pediatrics. We report the results of the first clinical trial of oral viscous budesonide (OVB) performed in children with EoE after repaired esophageal atresia (EoE-EA). METHODS: This open-label, single-arm, phase 2 clinical trial with randomized pharmacokinetic sampling, was conducted at the Bambino Gesù Children's Hospital between September 2019 and June 2021. EoE-EA patients received an age-banded dose of OVB twice daily for 12 weeks and were endoscopically evaluated. The primary endpoint was the rate of patients achieving histological remission. Secondary endpoints included clinical and endoscopic benefit after treatment, and safety assessments. RESULTS: Eight consecutive EA-EoE patients were enrolled (median age 9.1 years, interquartile range 5.5). Of these, 5 received 0.8 mg and 3 received 1.0 mg twice daily of OVB. Histological remission was obtained in all but 1 patient (87.5%). The clinical score showed significant improvement at the end of treatment in all patients. No endoscopic features of EoE were found after treatment. No treatment-emergent adverse event occurred. CONCLUSION: OVB is an effective, safe, and well-tolerated formulation of budesonide for use in pediatric patients with EoE-EA.

The Investigational Clinical Center: a clinical-supportive and patient-centered trial unit model. Ten years of experience through normal and pandemic times of a large pediatric trial center in Italy.

Evidence-based medicine relies on appropriately designed, conducted and reported clinical trials (CTs) to provide the best proofs of efficacy and safety for pharmacological and non-pharmacological treatments. Modern clinical research features high complexity and requires a high workload for the management of trials-related activities, often hampering physicians' participation to clinical trials. Dealing with children in clinical research adds complexity: rare diseases, parents or legal guardian reluctance to engage and recruitment difficulties are major reasons of pediatric trials failure.However, because in pediatrics many treatments are prescribed off-label or are lacking, well-designed clinical trials are particularly needed. Clinical Trial Units (CTUs) are indeed an important asset in the implementation of clinical trials, but their support to investigators is limited to administrative and non-clinical tasks. In this paper we present the model of the Investigational Clinical Center (ICC) of the Bambino Gesù Children's Hospital in Rome. The ICC includes clinicians supporting the Principal Investigators for clinical management of enrolled patients in compliance of Good Clinical Practice, the legal framework of Clinical Trials. Furthermore, we present 10 years' experience in pediatric clinical trials and how it has been affected in 2020 by the COVID-19 pandemic. The activity of the ICC has been evaluated according to specific metrics of performance. The ICC model offers a complete support, helping investigators, patients and their families to overcome majority of barriers linked to clinical research, even in time of pandemic. We propose this organization as an innovative model for total-supportive and patient-centered clinical trial implementation.