## Protocol Section
### Identification Module
**NCT ID:** NCT06435481

**Brief Title:** Tolerability and Acceptance of Two Oral Hydrocortisone Compounding Formulation for Pediatrics

**Official Title:** Tolerability and Acceptance of Two Oral Hydrocortisone Compounding Formulation for Pediatrics

#### Organization Study ID Info
**ID:** HIDROGUM21
#### Organization
**Class:** OTHER
**Full Name:** Hospital Universitari Vall d'Hebron Research Institute
#### Secondary ID Infos
**ID:** 2021-001069-20
**Type:** EUDRACT_NUMBER
### Status Module
#### Completion Date
**Date:** 2026-09

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-30

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-24

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2025-09

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-09

**Type:** ESTIMATED

**Status Verified Date:** 2024-04

#### Study First Post Date
**Date:** 2024-05-30
**Type:** ACTUAL
**Study First Submit Date:** 2024-04-29
**Study First Submit QC Date:** 2024-05-24
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Hospital Universitari Vall d'Hebron Research Institute

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Is US Export:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** 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.

**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.

### Conditions Module

**Conditions:**

- Adrenal Insufficiency

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** CROSSOVER

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 35

**Type:** ESTIMATED

**Phases:**

- PHASE4

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 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.

**Intervention Names:**

- Drug: 3D printed chewable formulation of hydrocortisone

**Label:** Chewable Tablet Group

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** 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.

**Intervention Names:**

- Drug: Oral suspension of hydrocortisone

**Label:** Oral Suspension Group

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Chewable Tablet Group

**Description:** 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.

**Name:** 3D printed chewable formulation of hydrocortisone

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Oral Suspension Group

**Description:** Administration of a standard hydrocortisone oral suspension. The solution, based on simple syrup, contains 1mg of hydrocortisone per milliliter.

**Name:** Oral suspension of hydrocortisone

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Tolerability will be assessed using a five-point questionnaire, while acceptability will be measured using the hedonic facial scale.

**Measure:** Tolerability and acceptance of the two compounded oral hydrocortisone formulations

**Time Frame:** 6 months

#### Secondary Outcomes

**Description:** 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.

**Measure:** Efficacy, compliance and safety of each hydrocortisone formulation

**Time Frame:** 6 months

### Eligibility Module

**Eligibility Criteria:** 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.

**Maximum Age:** 18 Years

**Minimum Age:** 6 Years

**Sex:** ALL

**Standard Ages:**

- CHILD

- ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** carlosjavier.parramon@vallhebron.cat

**Name:** Carlos Javier Parramón Teixidó

**Phone:** +3492746017

**Phone Ext:** 6017

**Role:** CONTACT

**Contact 2:**

**Email:** ceic@vhir.org

**Name:** Hospital Universitari Vall d'Hebron Research Institute

**Phone:** +34934894010

**Phone Ext:** 4010

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Barcelona

**Contacts:**

***Contact 1:***

- **Email:** carlosjavier.parramon@vallhebron.cat

- **Name:** Carlos Javier Parramón Teixidó

- **Phone:** +3492746017

- **Role:** CONTACT

**Country:** Spain

**Facility:** Hospital Universitari Vall d'Hebron

**Zip:** 08035

#### Overall Officials

**Official 1:**

**Affiliation:** Hospital Vall d'Hebron

**Name:** Hospital Universitari Vall d'Hebron

**Role:** STUDY_CHAIR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000000307

- Term: Adrenal Gland Diseases

- ID: D000004700

- Term: Endocrine System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC19

- Name: Gland and Hormone Related Diseases

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M3661

- Name: Adrenal Insufficiency

- Relevance: HIGH

- As Found: Adrenal Insufficiency

- ID: M3659

- Name: Adrenal Gland Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M7862

- Name: Endocrine System Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000000309

- Term: Adrenal Insufficiency

### Intervention Browse Module - Ancestors

- ID: D000000893

- Term: Anti-Inflammatory Agents

### Intervention Browse Module - Browse Branches

- Abbrev: Infl

- Name: Anti-Inflammatory Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: PhSol

- Name: Pharmaceutical Solutions

- Abbrev: Derm

- Name: Dermatologic Agents

### Intervention Browse Module - Browse Leaves

- ID: M9912

- Name: Hydrocortisone

- Relevance: HIGH

- As Found: Group A

- ID: M155245

- Name: Hydrocortisone 17-butyrate 21-propionate

- Relevance: HIGH

- As Found: Group A

- ID: M228609

- Name: Hydrocortisone acetate

- Relevance: HIGH

- As Found: Group A

- ID: M263259

- Name: Hydrocortisone hemisuccinate

- Relevance: HIGH

- As Found: Group A

- ID: M21860

- Name: Pharmaceutical Solutions

- Relevance: LOW

- As Found: Unknown

- ID: M242077

- Name: Hydrocortisone-17-butyrate

- Relevance: LOW

- As Found: Unknown

- ID: M4217

- Name: Anti-Inflammatory Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000006854

- Term: Hydrocortisone

- ID: C000033014

- Term: Hydrocortisone 17-butyrate 21-propionate

- ID: C000021650

- Term: Hydrocortisone acetate

- ID: C000007133

- Term: Hydrocortisone hemisuccinate

### Misc Info Module

- Version Holder: 2024-05-31
