Pharmacokinetics, Efficacy, Tolerability and Safety of Different Budesonide Oral Gel Doses in Adults' Subjects of Both Genders With Eosinophilic Esophagitis (EoE) (BESIDE)

A Phase I/II, Multicenter, Double-blind, Parallel, Randomized Trial to Assess Pharmacokinetics, Efficacy, Tolerability and Safety of Different Budesonide Oral Gel Doses in Adults Subjects of Both Genders With Eosinophilic Esophagitis (EoE)

A phase I/II, multicenter, double-blind, parallel, randomized trial to assess pharmacokinetics, efficacy, tolerability and safety of different budesonide oral gel doses in adults subjects of both genders with eosinophilic esophagitis (EoE)

Study Overview

• Status: Not yet recruiting
• Conditions: Eosinophilic Esophagitis
• Intervention / Treatment: Drug: Budesonide Gel

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects able to read, understand and sign the Informed Consent Form (ICF) approved by Ethical Committee;
• Male and female subjects aged between 18 and 75 years old;
• Body weight between 60-100 kg;
• Body mass index (BMI) ≥ 18.5 and ≤ 29.9 kg/m2;
• Non-childbearing potential female subjects. Childbearing potential is defined as: post-menopausal women (defined as 12 months of amenorrhea or more), hysterectomized women, oophorectomized (bilateral) women and/or those who underwent tubal ligation;
• Female participants of childbearing potential who test negative for the pregnancy test on the day of administration of the first dose of the drug (Visit 1), as well as throughout the clinical trial;
• Female participants who practice adequate contraception or who abstain from all activities that could result in pregnancy for at least 28 days before administering the first dose of the drug (Visit 1);
• Female participants who agree to continue adequate contraception for 1 month after administration of the last dose of the investigational drug;
• Participants diagnosed with EoE, verified from a combination of symptoms compatible with EoE and histological finding greater than 15 eosinophils per high-power field in at least one esophageal mucosal biopsy;
• Participants unresponsive to stable dose of proton-pump inhibitor (PPI).

Exclusion Criteria:

• Subjects with a malignancy history within the last 5 years, except from successfully treated basal cell carcinoma;
• History of esophageal stenosis requiring dilation and/or stenosis at endoscopy not allowing to pass the endoscope;
• Subjects with a eosinophilic gastroenteritis diagnosis (presence of eosinophilic infiltrate in gastric antrum and duodenum);
• Subjects with a reflux esophagitis history;
• Subject with a previous serious asthma diagnosis;
• Subjects with a gastroesophageal tract disease that, at the investigator's discretion, is deemed as an obstacle to take part in the trial;
• People with chronic diseases on regular drugs that, in the investigator's opinion, may interfere with the trial;
• Medical conditions such as serious heart or lung diseases preventing the safe performance of endoscopy;
• Subjects with conditions known to be related to esophageal eosinophilia, including Crohn's disease, Churg-Strauss, achalasia and hypereosinophilic syndrome;
• Subjects who have been on oral, intranasal or systemic corticosteroid at least 15 days prior to trial start;
• Smoker of having quit smoking less than 6 months ago;
• Have a history of excessive alcohol intake for at least 6 months prior to trial start (intake of 5 or more alcoholic beverages in one day or 15 or more alcoholic beverages per week);
• Subjects having 5 or more cups of tea or coffee per day and who cannot abstain from them for the trial period;
• Be on CYP3A4 inhibitors, such as ketoconazole and grapefruit juice;
• Electrocardiogram (ECG) findings that, in the investigator's opinion, may jeopardize participation in the trial;
• History or presence of gastrointestinal or liver disease or other condition interfering with drug absorption, distribution, excretion or metabolism;
• Subjects with hypersensitivity or contraindication of using any formulation components;
• Subjects who have been part of trial protocols in the last 12 (twelve) months (CNS Resolution 251, dated August 7, 1997, item III, sub-item J);
• Have donated blood (> 500 mL) or undergone major surgery within the 3 months prior to the ICF signature date;
• Have been vaccinated for the 30 days prior to admission;
• Clinical evidence of infectious process potentially contributing for dysphagia (candidiasis, cytomegalovirus (CMV), herpes);
• Other dysphagia cause identified at endoscopy (peptic stenosis, web, ring, achalasia, esophageal neoplasm);
• Breastfeeding subjects, who plan to become pregnant or with a positive pregnancy test during the trial;
• Any medical condition or laboratory change that, in the investigator's opinion, may jeopardize participation in the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Low dose	Drug: Budesonide Gel; Twice daily regimen
Experimental: Group 2; Middle dose	Drug: Budesonide Gel; Twice daily regimen
Experimental: Group 3; High dose	Drug: Budesonide Gel; Twice daily regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determination of Pharmacokinetic Profiles	Peak Plasma Concentration (Cmax)	First 24 hours after a single drug dose administration
Determination of Pharmacokinetic Profiles	Area under the plasma concentration versus time curve (AUC)	First 24 hours after a single drug dose administration
Determination of Pharmacokinetic Profiles	Half-life (T1/2)	First 24 hours after a single drug dose administration
Determination of Pharmacokinetic Profiles	Oral clearance (CL/F)	First 24 hours after a single drug dose administration
Proportion of subjects reaching a histological response	≤ 6 eosinophils per high power field	8 weeks of treatment
Improvement in dysphagia symptoms consistent with the disease	EAT (Eating Assessment Tool) -10 questionnaire	8 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of non-serious and serious adverse events rate		Through 8 weeks
Quality of life assessment of subjects	WHOQOL-bref questionnaire	Through 8 weeks

Collaborators and Investigators

• Sponsor: Bazell Pharma AG

Study record dates

Study Major Dates

• Study Start (Estimated): July 31, 2024
• Primary Completion (Estimated): April 30, 2025
• Study Completion (Estimated): April 30, 2025

Study Registration Dates

• First Submitted: January 3, 2022
• First Submitted That Met QC Criteria: January 13, 2022
• First Posted (Actual): January 28, 2022

Study Record Updates

• Last Update Posted (Estimated): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Immune System Diseases; Hypersensitivity, Immediate; Hematologic Diseases; Gastrointestinal Diseases; Gastroenteritis; Hypersensitivity; Esophageal Diseases; Leukocyte Disorders; Eosinophilia; Eosinophilic Esophagitis; Esophagitis; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Budesonide
• Other Study ID Numbers: BAZ006-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is not a plan to make individual participant data (IPD) available

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No