Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Budesonide Extended-release Tablets in Pediatric Subjects Aged 5 to 17 Years With Active, Mild to Moderate Ulcerative Colitis

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, multicenter, study to evaluate the efficacy, safety, and pharmacokinetics (PK) of budesonide extended-release tablets for the induction of remission in pediatric subjects, with active, mild to moderate ulcerative colitis (UC). Subjects will be permitted to continue taking background oral or rectal 5-aminosalicylate (5-ASA) products.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Budesonide Extended-release Tablets n Pediatric Subjects Aged 5 to 17 Years With Active, Mild to Moderate Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Low Dose Budesonide
* Drug: High Dose Budesonide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Established diagnosis of UC is based on: Clinical history Characteristic endoscopic findings Histopathology results from biopsies Age 5 to 17 years, inclusive, at Screening. Subjects should weigh greater than 13.6 kg at Baseline. Active UC of mild or moderate severity, defined as a total Mayo score between 4 and 10, inclusive, with rectal bleeding subscore of ≥ 1, stool frequency subscore of ≥1 and an endoscopy subscore of ≥ 1. If on a background oral or rectal 5-ASA, the dose and formulation have remained unchanged for at least 6 weeks prior to Visit 2 (randomization), Baseline and the subject is willing to remain on the same formulation and dose for the duration of the study. Exclusion Criteria: Current or prior diagnosis of Crohn's disease or indeterminate colitis. Limited distal proctitis (disease involving only the first 15 centimeters or less proximal to the anal verge. Severe UC, defined as total Mayo score >10. Not currently in an active phase or flare, defined as a total Mayo score <4, or Mayo score between 4 and 10, but Mayo subscore of 0 for rectal bleeding, stool frequency or endoscopy. Infectious colitis (based on positive microbiologic tests at Screening) or any recent history of infectious colitis (within 30 days prior to Screening). Prior gastrointestinal surgery, except appendectomy or hernia (e.g., inguinal, umbilical). NOTE: Prior cholecystectomy is not exclusionary if more than 1 year prior to Screening. Evidence or history of toxic megacolon or bowel resection.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 17 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Dose Budesonide<br> | Drug: Low Dose Budesonide<br>* 3 milligrams once daily for ages 5 to 11 years 11 months. 6 milligrams once daily for ages 12 to 17 years.<br>|
| Experimental: High Dose Budesonide<br> | Drug: High Dose Budesonide<br>* 6 milligrams once daily for ages 5 to 11 years 11 months. 9 milligrams once daily for ages 12 to 17 years.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Matching placebo once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary efficacy endpoint is the proportion of subjects who achieve clinical remission at Day 56, defined as a total Mayo score of ≤ 1 with subscores of 0 for both rectal bleeding and stool frequency, and a subscore of ≤ 1 for endoscopy. | The primary efficacy endpoint is the proportion of subjects who achieve clinical remission at Day 56, defined as a total Mayo score of ≤ 1 with subscores of 0 for both rectal bleeding and stool frequency, and a subscore of ≤ 1 for endoscopy. The Mayo score is a composite index score based on 4 components: stool frequency (subject reported), rectal bleeding (subject reported), findings of endoscopy, and the physician's rating of disease activity. Each component is scored from 0 to 3, with total scores range from 0 to 12 with higher scores indicating more severe disease. | 56 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects who achieve a Mayo rectal bleeding subscale score of 0 at Day 56. | Proportion of subjects who achieve a Mayo rectal bleeding subscale score of 0 at Day 56. The Mayo score is a composite index score based on 4 components: stool frequency (subject reported), rectal bleeding (subject reported), findings of endoscopy, and the physician's rating of disease activity. Each component is scored from 0 to 3, with total scores range from 0 to 12 with higher scores indicating more severe disease. | 56 days | 
| Proportion of subjects who achieve a Mayo stool frequency subscale score of 0 at Day 56. | Proportion of subjects who achieve a Mayo stool frequency subscale score of 0 at Day 56. The Mayo score is a composite index score based on 4 components: stool frequency (subject reported), rectal bleeding (subject reported), findings of endoscopy, and the physician's rating of disease activity. Each component is scored from 0 to 3, with total scores range from 0 to 12 with higher scores indicating more severe disease. | 56 days | 
| Proportion of subjects who achieve a Mayo endoscopy subscale score of 0 or 1 at Day 56. | Proportion of subjects who achieve a Mayo endoscopy subscale score of 0 or 1 at Day 56. The Mayo score is a composite index score based on 4 components: stool frequency (subject reported), rectal bleeding (subject reported), findings of endoscopy, and the physician's rating of disease activity. Each component is scored from 0 to 3, with total scores range from 0 to 12 with higher scores indicating more severe disease. | 56 days |