Tolerability and Acceptance of Two Oral Hydrocortisone Compounding Formulation for Pediatrics

The study aims to evaluate the tolerability and acceptance of two compounded formulations of hydrocortisone prepared in the Vall d'Hebron University Hospital (VHUH) Pharmacy Service: one, an oral suspension and the other, chewable tablets prepared using a volume dosing device (M3DIMAKER 3D printer). The main goal is to enhance patient care and adherence among pediatric patients.

This prospective, experimental study employs a randomized, crossover design and will take place solely at VHUH. Approximately 25-30 eligible patients diagnosed with adrenal hyperplasia, isolated primary adrenal insufficiency, or panhypopituitarism will be recruited. Each patient will receive each hydrocortisone formulation for a period of 3 months, totaling 6 months of treatment per patient. All patients will receive the medication at their usual dose and both formulations to assess tolerability and acceptance.

Study Overview

• Status: Not yet recruiting
• Conditions: Adrenal Insufficiency
• Intervention / Treatment: Drug: 3D printed chewable formulation of hydrocortisone; Drug: Oral suspension of hydrocortisone

Detailed Description

Adrenal insufficiency arises from inadequate synthesis of adrenal hormones, with primary, secondary, or tertiary forms depending on the defect's location-adrenal, pituitary, or hypothalamic. Hydrocortisone (17-Hydroxycorticosterone) is the preferred cortisol replacement.

Pediatric hydrocortisone formulations are not commercially available in any presentation. Consequently, compounded formulations are prepared as standard practice. Vall d'Hebron University Hospital's Pharmacy Service currently provides a liquid hydrocortisone formulation for these patients. While liquid formulations are often preferred due to their better dose adjustment and improved acceptability by pediatric patients, they have limitations such as shorter shelf life, possible special storage conditions, and taste problems due to bitter active ingredients. In some cases, particularly for chronic treatments with established and constant doses, other options such as capsules may be considered. Capsules offer longer stability, longer expiration dates, and do not require special storage conditions.

In this context, this study aims to determine the tolerability and acceptance of a new solid magistral formula in the form of chewable hydrocortisone tablets, prepared using a volume dosing device (M3DIMAKERTM 3D printer), compared to the usually preferred liquid formulation. Each of the formulations will be administered for three months. Evaluating the results will allow us to improve assistance to pediatric patients by offering the formulation with better tolerability and acceptance. The study will take place at Vall d'Hebron University Hospital, led by the Pharmacy Service in collaboration with the Pediatric Endocrinology Service.

• Study Type: Interventional
• Enrollment (Estimated): 35
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Carlos Javier Parramón Teixidó; Phone Number: 6017 +3492746017; Email: carlosjavier.parramon@vallhebron.cat
• Study Contact Backup: Name: Hospital Universitari Vall d'Hebron Research Institute; Phone Number: 4010 +34934894010; Email: ceic@vhir.org

Study Locations

• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
    • Contact: Carlos Javier Parramón Teixidó; Phone Number: +3492746017; Email: carlosjavier.parramon@vallhebron.cat

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Outpatients of both sexes, ≥ 6 years old without swallowing problems and up to 17 years old, at the time of signing the informed consent document by parent(s) or guardian(s) and/or patients.
• Diagnosis of adrenal hyperplasia or isolated primary adrenal insufficiency or panhypopituitarism (secondary or tertiary adrenal insufficiency).

Exclusion Criteria:

• Known hypersensitivity to any of the excipients in the formulation of hydrocortisone.
• Any disorder or situation (decompensation) that, in the opinion of the investigating physician, poses a risk of non-compliance with the treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chewable Tablet Group; Group of patients receiving a new hydrocortisone formulation in the form of chewable tablets. Patients in this group will take the 3D printed chewable tablets orally for a duration of three months.	Drug: 3D printed chewable formulation of hydrocortisone; Administration of a novel hydrocortisone formulation provided as chewable tablets. Each tablet, manufactured with a volume dosing device (3D printer), contains a precise dosage of hydrocortisone.
Active Comparator: Oral Suspension Group; Group of patients receiving the standard hydrocortisone formulation in the form of an oral solution. Patients in this group will orally ingest the solution over a period of three months.	Drug: Oral suspension of hydrocortisone; Administration of a standard hydrocortisone oral suspension. The solution, based on simple syrup, contains 1mg of hydrocortisone per milliliter.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability and acceptance of the two compounded oral hydrocortisone formulations	Tolerability will be assessed using a five-point questionnaire, while acceptability will be measured using the hedonic facial scale.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy, compliance and safety of each hydrocortisone formulation	Efficacy will be assessed by the variation in hydrocortisone dosage as a percentage compared to the previous visit, the presence of intercurrent issues, and emergency room visits resulting from the underlying condition. Treatment adherence will be estimated through monitoring medication dispensations from the Pharmacy Service and counting returned medication. Safety will be evaluated by reporting potential adverse effects of treatment, the presence of intercurrent issues, and emergency room visits during follow-up.	6 months

Collaborators and Investigators

• Sponsor: Hospital Universitari Vall d'Hebron Research Institute
• Investigators: Study Chair: Hospital Universitari Vall d'Hebron, Hospital Vall D'Hebron

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2024
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: April 29, 2024
• First Submitted That Met QC Criteria: May 24, 2024
• First Posted (Actual): May 30, 2024

Study Record Updates

• Last Update Posted (Actual): May 30, 2024
• Last Update Submitted That Met QC Criteria: May 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Adrenal Gland Diseases; Adrenal Insufficiency; Anti-Inflammatory Agents; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate
• Other Study ID Numbers: HIDROGUM21; 2021-001069-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No