Clinical trial NCT00762073: Dose-Ranging Study of Oral Viscous Budesonide in Pediatrics With Eosinophilic Esophagitis
Official title: Oral Viscous Budesonide Suspension (MB-7) in Subjects With Eosinophilic Esophagitis: A Randomized, Placebo-Controlled, Dose-Ranging Study in Children and Adolescents
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Eosinophilic Esophagitis (EoE)
Keywords: eosinophilic esophagitis
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2008-09-30
Enrollment: 82
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, placebo-controlled, parallel-arm, dose-ranging study in subjects with eosinophilic esophagitis, 2-18 years of age. Eligible subjects will be randomized into one of four treatment groups. The Treatment Period will be 12 weeks during which subjects will visit the clinic at study weeks 0 (Baseline Visit), 2, 4, 8 and 12 (Final Treatment Evaluation) for clinical symptom assessment and safety evaluation (including adverse events and vital signs). All study treatments (active drug and placebo) will be administered orally twice daily during the Treatment Period, once in the morning after breakfast and once in the evening at bedtime.


Eligibility criteria: Inclusion Criteria:

* Male and female subjects between the ages of 2-18 years, inclusive
* History of clinical symptoms of esophageal dysfunction intermittently or continuously
* Histologic evidence of EoE with a peak eosinophil count of greater than or equal to 20 eosinophils per HPF, from two or more levels of the esophagus, within six weeks prior to the Baseline Visit
* At the Baseline Visit, subjects must have symptoms with a total EoE Clinical Symptom Score of greater than or equal to 3
* Willingness and ability to continue the dietary therapy, environmental therapy, and/or medical regimens (including gastric acid suppression, if any) in effect at the Screening Visit
* Females of childbearing potential must have a negative serum pregnancy test (beta human chorionic gonadotropin) prior to randomization into the study and sexually active subjects must agree to continue acceptable birth control measures throughout the duration of the study
* Written informed consent (parent or legal guardian) and, as appropriate, subject assent

Exclusion Criteria:

* Current use of immunomodulatory therapy (or anticipated use within 12 weeks following the Baseline Visit)
* Diagnosis of inflammatory bowel disease
* Chronic viral infection or immunodeficiency condition (current)
* Use of swallowed topical corticosteroids for EoE in the 1 month prior to the biopsy required for entrance to this study or at any time between the biopsy and the Baseline Visit
* Use of systemic (oral or parenteral) corticosteroid within 1 month prior to the biopsy required for entrance to this study or at any time between the biopsy and the Baseline Visit
* Morning plasma cortisol level below the lower limit of normal (per Central Laboratory reference range) at the Screening Visit
* Upper gastrointestinal bleeding within 1 month prior to the Screening Visit or between the Screening Visit and Baseline Visit
* Current use of anticoagulants
* Current disease of the gastrointestinal tract aside from the current EoE diagnosis
* Evidence of concurrent eosinophilic gastritis, enteritis, colitis, or proctitis
* Evidence of active infection with Helicobacter pylori
* Evidence of unstable asthma or changes in asthma or allergic rhinitis therapy within 1 month prior to the biopsy required for entrance to this study
* Any female who is pregnant, who is planning to become pregnant, or who is breast-feeding
* Current evidence or history of hypersensitivity or idiosyncratic reaction to budesonide or any other ingredients of the study medication
* Current evidence of oropharyngeal or esophageal candidiasis
* Receipt of an investigational drug within 30 days prior to the biopsy required for entrance to this study
* Any condition or abnormality that, in the opinion of the Principal Investigator, would compromise the safety of the subject or successful conduct of the study

Primary outcomes:
measure: Percent of Participants Who Responded to Therapy
timeFrame: 12 weeks after the start of treatment
Secondary outcomes:
measure: Percent of Participants With Histologic Response
timeFrame: 12 weeks after the start of treatment
measure: Percent of Participants With Histologic Remission
timeFrame: 12 weeks after the start of treatment
measure: Percent Change From Baseline in Peak Eosinophil Count
timeFrame: Baseline, 12 weeks after the start of treatment
measure: Change From Baseline in Endoscopy Score
timeFrame: Baseline, 12 weeks after the start of treatment
measure: Percent of Participants With Clinical Response
timeFrame: 12 weeks after the start of treatment
measure: Percent of Participants With Clinical Remission
timeFrame: 12 weeks after the start of treatment
measure: Percent Change From Baseline in Eosinophilic Esophagitis (EoE) Clinical Symptom Score (CSS)
timeFrame: Baseline, 12 weeks after the start of treatment
measure: Change From Baseline in Physician's Global Assessment Score of Disease Severity
timeFrame: Baseline, 12 weeks after the start of treatment
measure: Maximum Plasma Concentration (Cmax) of Budesonide
timeFrame: Week 2, 4, or 8, or at the Final Treatment Evaluation
measure: Time to Maximum (Tmax) And Half Maximum (T1/2) Plasma Concentration of Budesonide
timeFrame: Week 2, 4, or 8, or at the Final Treatment Evaluation
measure: Area Under The Plasma Concentration-Time Curve (AUC) of Budesonide From Time Zero to Time of The Last Measurable Concentration (AUC0-last)
timeFrame: Week 2, 4, or 8, or at the Final Treatment Evaluation
measure: Percent of Participants With Potential Corticosteroid-Related Treatment-Emergent Adverse Events (TEAEs)
timeFrame: 15 weeks after the start of treatment
measure: Mean Change in Blood Pressure (BP) at End of Treatment
timeFrame: Baseline, 12 weeks after the start of treatment
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital
state: California
city: Aurora
country: United States
facility: The Children's Hospital
state: Colorado
city: Atlanta
country: United States
facility: Emory University-Emory Children's Center
state: Georgia
city: Atlanta
country: United States
facility: Children's Center for Digestive Healthcare
state: Georgia
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: Park Ridge
country: United States
facility: Center for Children's Digestive Health
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Omaha
country: United States
facility: The Center for Human Nutrition
state: Nebraska
city: Las Vegas
country: United States
facility: Pediatric Gastroenterology and Nutrition Associates
state: Nevada
city: Mays Landing
country: United States
facility: South Jersey Pediatric Gastroenterology
state: New Jersey
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Greenville
country: United States
facility: Children's Center for Digestive Health
state: South Carolina
city: Norfolk
country: United States
facility: Children's Hospital of the King's Daughters
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University, Medical College of Virginia
state: Virginia
city: Roanoke
country: United States
facility: Carilion Pediatric Gastroenterology
state: Virginia
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Gupta SK, Hill M, Vitanza JM, Farber RH, Desai NK, Williams J, Song IH. Pharmacokinetics of Budesonide Oral Suspension in Children and Adolescents With Eosinophilic Esophagitis. J Pediatr Gastroenterol Nutr. 2022 Aug 1;75(2):186-191. doi: 10.1097/MPG.0000000000003482. Epub 2022 Jun 6.
citation: Gupta SK, Vitanza JM, Collins MH. Efficacy and safety of oral budesonide suspension in pediatric patients with eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2015 Jan;13(1):66-76.e3. doi: 10.1016/j.cgh.2014.05.021. Epub 2014 Jun 4.