Dose Ranging Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Budesonide Rectal Foam in Pediatric Patients Aged 5 to 17 Years With Active, Mild to Moderate Distal Ulcerative Colitis

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the efficacy (as measured by induction of remission) of two dose levels (low and high) per age group (5 to <12 and 12 to ≤17 years) of budesonide rectal foam as compared to an equivalent volume of rectally administered placebo foam over the same dosing schedule, in pediatric subjects with active, mild to moderate distal ulcerative colitis (UC).

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Dose Ranging Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Budesonide Rectal Foam BID for 2 Weeks, Followed by QD for 4 Weeks, in Pediatric Patients Aged 5 to 17 Years With Active, Mild to Moderate Distal Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: High dose budesonide rectal foam
* Drug: Low dose budesonide rectal foam
* Drug: Matching placebo rectal foam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and Female (non-pregnant and non-lactating) 5 to ≤17 years of age at Screening. Established diagnosis of UC, based on clinical history, characteristic endoscopic findings, and histopathology results from biopsies. Disease limited to the distal colon and rectum, (disease involving only the first 15 centimeters or less proximal to the anal verge). Active, distal UC of mild or moderate severity, defined as a Modified Mayo Clinic Score (mMCS) between 4 and 8, inclusive, that includes an endoscopy subscore ≥ 2 and a rectal bleeding subscore ≥ 1. If on a background oral 5-ASA, the dose and formulation have remained unchanged for at least 6 weeks prior to Visit 2 (Run-In) and the subject is willing to remain on the same dosage form and regimen for the duration of the study. Exclusion Criteria: Current or prior diagnosis of Crohn's disease or indeterminate colitis. Ulcerative colitis involving the proximal colon - i.e, the sigmoid, left, transverse, and/or ascending colon and cecum; Severe UC, defined as an mMCS > 8. Infectious colitis (based on positive microbiologic tests at Screening) or any recent history of infectious colitis (within 30 days of 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. Active proctologic pathology such as hemorrhoids, fistulas and fissures or other historical anatomic problems which would impair rectal administration (e.g., cloaca, imperforate anus history)

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: High dose budesonide rectal foam<br> | Drug: High dose budesonide rectal foam<br>* Twice a day for 2 weeks, then once a day for 4 weeks<br>|
| Experimental: Low dose budesonide rectal foam<br> | Drug: Low dose budesonide rectal foam<br>* Twice a day for 2 weeks, then once a day for 4 weeks<br>|
| Placebo Comparator: Matching placebo rectal foam<br> | Drug: Matching placebo rectal foam<br>* Twice a day for 2 weeks, then once a day for 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with clinical remission | Clinical remission based on the modified Mayo Clinic Score, defined as an endoscopy score ≤ 1 (excluding friability), a rectal bleeding subscore of 0, and at least a 1-point decrease in stool frequency subscore from Baseline to achieve a stool frequency subscore ≤ 1. Each component is scored from 0 to 3, with total scores ranging from 0 to 9, with higher scores indicating more severe disease. | Day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants who achieve a rectal bleeding subscale score of 0 at the end of six weeks of treatment | Scored from 0 to 3, with higher scores indicating more severe disease. | Day 42 | 
| Proportion of participants who achieve a stool frequency subscale score of 0 at the end of six weeks of treatment. | Scored from 0 to 3, with higher scores indicating more severe disease. | Day 42 | 
| Proportion of subjects who achieve an endoscopy subscale score of 0 or 1 at the end of six weeks of treatment. | Scored from 0 to 3, with higher scores indicating more severe disease. | Day 42 |