Dose-Ranging Study of Oral Viscous Budesonide in Pediatrics With Eosinophilic Esophagitis

NCT00762073 | Completed Phase 2 Results

• 1 other identifier: MPI-101-01
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 20

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.

Conditions

Eosinophilic Esophagitis (EoE)

Keywords

eosinophilic esophagitis

Outcome Measures

Primary Outcomes (1)

• Percent of Participants Who Responded to Therapy

  Response was defined as a ≥50% reduction from baseline in the eosinophilic esophagitis (EoE) clinical symptom score (CSS) and a reduction in peak eosinophil count to ≤6/high power field (light microscopy) from esophageal biopsies collected at the final evaluation. The EoE CSS, scored from 0 to 18 by a doctor, assessed 6 categories: 1) heartburn, 2) abdominal pain, 3) nocturnal awakening with symptoms, 4) nausea, regurgitation, or vomiting, 5) anorexia or early satiety, and 6) dysphagia, odynophagia, or food impaction (a severe symptom). Each domain was scored as follows, based on symptoms in the 2 weeks prior to the assessment: 0 = No symptoms and no coping behaviors required; 1 = Mild: Symptoms limited to 1-3 days or no symptoms because coping behaviors were required to avoid symptoms; 2 = Moderate: Symptoms on \>3 days, with or without minor coping behaviors; 3 = Severe: Symptoms interfered with activities of daily living or symptoms persisted and required major coping behaviors.

  12 weeks after the start of treatment

Secondary Outcomes (13)

• Percent of Participants With Histologic Response

  12 weeks after the start of treatment

• Percent of Participants With Histologic Remission

  12 weeks after the start of treatment

• Percent Change From Baseline in Peak Eosinophil Count

  Baseline, 12 weeks after the start of treatment

• Change From Baseline in Endoscopy Score

  Baseline, 12 weeks after the start of treatment

• Percent of Participants With Clinical Response

  12 weeks after the start of treatment

Study Arms (4)

1

PLACEBO COMPARATOR

Drug: placebo

2

EXPERIMENTAL

Low Dose Group

Drug: budesonide

3

EXPERIMENTAL

Medium Dose Group

Drug: budesonide

4

EXPERIMENTAL

High Dose Group

Drug: budesonide

Interventions

budesonide DRUG

oral suspension

2; 3; 4

placebo DRUG

oral suspension matching budesonide

1

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Shire: lead

Study Sites (20)

Phoenix Children's Hospital

Phoenix, Arizona, 85006, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Stanford University Medical Center

Palo Alto, California, 94305, United States

Location

Rady Children's Hospital

San Diego, California, 92123, United States

Location

The Children's Hospital

Aurora, Colorado, 80045, United States

Location

Emory University-Emory Children's Center

Atlanta, Georgia, 30322, United States

Location

Children's Center for Digestive Healthcare

Atlanta, Georgia, 30342, United States

Location

Children's Memorial Hospital

Chicago, Illinois, 60614, United States

Location

Center for Children's Digestive Health

Park Ridge, Illinois, 60068, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

The Center for Human Nutrition

Omaha, Nebraska, 68105, United States

Location

Pediatric Gastroenterology and Nutrition Associates

Las Vegas, Nevada, 89109, United States

Location

South Jersey Pediatric Gastroenterology

Mays Landing, New Jersey, 08330, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Center for Digestive Health

Greenville, South Carolina, 29615, United States

Location

Children's Hospital of the King's Daughters

Norfolk, Virginia, 23507, United States

Location

Virginia Commonwealth University, Medical College of Virginia

Richmond, Virginia, 23219, United States

Location

Carilion Pediatric Gastroenterology

Roanoke, Virginia, 24013, United States

Location

Related Publications (2)

• 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.

  PMID: 35666852 DERIVED

• 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.

  PMID: 24907502 DERIVED

MeSH Terms

Conditions

Eosinophilic Esophagitis

Interventions

Budesonide

Condition Hierarchy (Ancestors)

Esophagitis; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Gastroenteritis; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2008
• First Posted: September 30, 2008
• Study Start: January 8, 2009
• Primary Completion: April 2, 2010
• Study Completion: April 2, 2010
• Last Updated: June 11, 2021
• Results First Posted: October 5, 2015

Record last verified: 2021-06

Locations

US (20)