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

Study Overview
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Brief Summary
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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)

Official Title
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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)

Conditions
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Eosinophilic Esophagitis

Intervention / Treatment
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* Drug: Budesonide Gel


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Low dose | Drug: Budesonide Gel<br>* Twice daily regimen<br>|
| Experimental: Group 2<br>Middle dose | Drug: Budesonide Gel<br>* Twice daily regimen<br>|
| Experimental: Group 3<br>High dose | Drug: Budesonide Gel<br>* Twice daily regimen<br>|

What is the study measuring?
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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 |