Efficacy and Safety of Budesonide Foam for Participants With Active Mild to Moderate Ulcerative Proctitis or Proctosigmoiditis

Study Overview
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Brief Summary
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The purpose of this study is to establish the efficacy profile of rectally administered budesonide foam, as compared to an equivalent volume of rectally administered placebo foam over the same dosing schedule, in participants who present with a diagnosis of active, mild to moderate, ulcerative proctitis (UP) or ulcerative proctosigmoiditis (UPS). During the study, eligible participants will be allowed to maintain previously established oral 5-aminosalicylic acid (5-ASA) treatment at doses up to 4.8 grams/day (g/day).

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Assess the Efficacy and Safety of Budesonide Foam (2 mg/25 mL BID for 2 Weeks, Followed by 2 mg/25 mL QD for 4 Weeks) Versus Placebo in Subjects With Active Mild to Moderate Ulcerative Proctitis or Proctosigmoiditis

Conditions
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Proctitis, Proctosigmoiditis

Intervention / Treatment
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* Drug: Budesonide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntarily sign written informed consent. Male or non-pregnant and non-lactating females. Confirmed diagnosis (by endoscopy procedure) of active, mild to moderate UP or UPS, with disease extending at least 5 centimeters (cm) but no further than 40 cm from the anal verge. Must possess a baseline Modified Mayo Disease Activity Index (MMDAI) score between 5 and 10. Exclusion Criteria: History or current diagnosis of Crohn's disease and indeterminate colitis. Prior gastrointestinal surgery except appendectomy and hernia. Concomitant active gastrointestinal disease or distortion of intestinal anatomy. History of diverticulitis, collagenous colitis, celiac disease, recurrent pancreatic or known gallbladder disease. Uncontrolled, previously diagnosed type 1 or 2 diabetes mellitus. Uncontrolled abnormal thyroid function. Unstable significant cardiovascular, endocrine, neurologic or pulmonary disease. Hemoglobin levels less than (<) 7.5 grams /deciliter (g/dL). History of sclerosing cholangitis, cirrhosis, or hepatic impairment. Renal disease manifested by greater than (>) 2.0 milligrams/deciliter (mg/dL) serum creatinine. History of avascular hip necrosis, active tuberculosis, ocular herpes simplex or ocular varicella zoster, malignant disease, and human immunodeficiency virus (HIV) or hepatitis B or C. Adrenal insufficiency. Active systemic or cutaneous infection or toxic megacolon, fistula, perforation or abscess. History of uncontrolled psychiatric disorders or seizure disorders. History of asthma requiring ongoing use of inhaled steroids. Recent history of drug or alcohol abuse. Positive stool test for bacterial pathogens, Clostridium difficile toxin, or ovum and parasites. Vaccination within 28 days prior to randomization. Allergies to budesonide or to any other items used in its preparation. Participation in another clinical trial in the past 30 days. Pregnant or at risk of pregnancy. Taking a prohibited medication. Some medications to treat UP/UPS are prohibited during participation in the study, including laxatives and anti-diarrhea medications; however, oral 5-ASA agents at doses up to 4.8 g/day and daily fiber supplements are allowed. Other medications (e.g., antibiotics, anti-seizure and anti-coagulant medicines) are also prohibited.

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Budesonide<br>Participants who were diagnosed with active mild to moderate UP or UPS, will receive 2 milligrams (mg)/25 milliliter (mL) of budesonide foam, rectally twice daily for a period of 2 weeks followed by 2 mg/25 mL of budesonide foam, rectally once daily for a period of 4 weeks. | Drug: Budesonide<br>* Budesonide will be administered as per the dose and schedule specified in the respective arm.<br>|
| Placebo Comparator: Placebo<br>Participants who were diagnosed with active mild to moderate UP or UPS will receive 25 mL of placebo matching to budesonide foam twice daily for a period of 2 weeks followed by once daily for a period of 4 weeks. | Drug: Placebo<br>* Placebo matching to budesonide will be administered as per the schedule specified in the respective arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved Remission | Remission was a combined assessment of clinical and endoscopic variables, defined as an endoscopy score of less than or equal to (<=) 1, a rectal bleeding score of 0, and an improvement or no change from baseline in stool frequency subscales of the Modified Mayo Disease Activity Index (MMDAI) at the end of 6 weeks of treatment. MMDAI was used to assess the overall disease activity for each participant. MMDAI evaluated 4 indices: stool frequency, rectal bleeding, physician's global assessment (PGA) and endoscopy findings each on a scale of 0 to 3 with a maximum total score of 12. Stool frequency MMDAI subscore ranged from 0-3, where 0 indicated normal number of stools per day and 3 indicated 5 or more stools than normal. Rectal bleeding MMDAI subscore ranged from 0-3, where 0 indicated no blood seen and 3 indicated blood alone passed. Endoscopy MMDAI subscore ranged from 0-3, where 0 indicated normal or inactive disease and 3 indicated severe disease (spontaneous bleeding, ulceration). | Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved a Rectal Bleeding MMDAI Subscale Score of 0 at End of Week 6 | The MMDAI was used to assess the overall disease activity for each participant. The MMDAI evaluated 4 indices:stool frequency, rectal bleeding, physician's global assessment and endoscopy findings each on a scale of 0 to 3 with a maximum total score of 12. Rectal bleeding MMDAI subscore ranged from 0-3, where 0 indicated no blood seen and 3 indicated blood alone passed. Missing data was imputed using LOCF method. | Week 6 | 
| Number of Scheduled Assessments With Rectal Bleeding Responder Classification | The MMDAI was used to assess the overall disease activity for each participant. The MMDAI evaluated 4 indices: stool frequency, rectal bleeding, physician's global assessment and endoscopy findings each on a scale of 0 to 3 with a maximum total score of 12. Rectal bleeding MMDAI subscore ranged from 0-3, where 0 indicated no blood seen and 3 indicated blood alone passed. Percentage of participants who were rectal bleeding responder at scheduled assessments were reported. Rectal bleeding responders were defined as those participants who achieved a rectal bleeding MMDAI subscale score of 0 during the treatment period. Missing data was imputed using LOCF method. | Weeks 1, 2, 4, and 6 | 
| Percentage of Participants Who Achieved an Endoscopy MMDAI Subscale Score of 0 or 1 at End of Week 6 | The MMDAI was used to assess the overall disease activity for each participant. The MMDAI evaluated 4 indices: stool frequency, rectal bleeding, physician's global assessment and endoscopy findings each on a scale of 0 to 3 with a maximum total score of 12. Endoscopy subscale ranged from 0-3, where 0 = normal or inactive disease, 1 = mild disease, 2 = moderate disease and 3 = severe disease (spontaneous bleeding, ulceration). Percentage of participants with normal or mild disease have been presented in this outcome measure. Missing data was imputed using LOCF method. | Week 6 | 
| Percentage of Participants Who Achieved a Score of 0 for Rectal Bleeding Subscale and a Combined Score of <=2 for Bowel Frequency and Physician's Global Assessment (PGA) in the MMDAI Subscales at End of Week 6 | The MMDAI was used to assess the overall disease activity for each participant. The MMDAI evaluated 4 indices: stool frequency, rectal bleeding, PGA and endoscopy findings each on a scale of 0 to 3 with a maximum total score of 12. Rectal bleeding subscore ranged from 0-3, where 0 indicated no blood seen and 3 indicated blood alone passed. Bowel frequency (BF) subscore ranged from 0-3, where 0 indicated normal number of stools per day and 3 indicated 5 or more stools than normal. PGA subscore ranged from 0-3, where 0 indicated normal disease and 3 indicated severe disease. Missing data was imputed using LOCF method. | Week 6 | 
| Percentage of Participants Who Achieved an MMDAI Total Score of <= 3 With Greater Than or Equal to (>=2) Points of Improvement From Baseline at the End of Week 6 | The MMDAI was used to assess the overall disease activity for each participant. The MMDAI evaluated 4 indices: stool frequency, rectal bleeding, physician's global assessment and endoscopy findings each on a scale of 0 to 3 with a maximum total score of 12. Rectal bleeding subscore ranged from 0-3, where 0 indicated no blood seen and 3 indicated blood alone passed. BF subscore ranged from 0-3, where 0 indicated normal number of stools per day and 3 indicated 5 or more stools than normal. Physician global assessment (PGA) subscore ranged from 0-3, where 0 indicated normal and 3 indicated severe disease. Endoscopy subscore ranged from 0-3, where 0 indicated normal and 3 indicated severe disease. MMDAI total score ranged from 0-12, where higher score indicated severe disease. Missing data was imputed using LOCF method. | Week 6 | 
| Percentage of Participants Who Achieved Improvement of >=1 Point From Baseline in the MMDAI Endoscopy Subscale Score at End of Week 6 | The MMDAI was used to assess the overall disease activity for each participant. The MMDAI evaluated 4 indices: stool frequency, rectal bleeding, PGA and endoscopy findings each on a scale of 0 to 3 with a maximum total score of 12. Endoscopy subscore ranged from 0-3, where 0 = normal or inactive disease, 1 = mild disease (erythema, decreased vascular pattern), 2 = moderate disease (marked erythema, absent vascular pattern, friability, erosions), and 3 = severe disease (spontaneous bleeding, ulceration). Missing data was imputed using LOCF method. | Week 6 | 
| Percentage of Participants Who Achieved Improvement of >=1 Point From Baseline in the MMDAI Rectal Bleeding Subscale Score at End of Week 6 | The MMDAI was used to assess the overall disease activity for each participant. The MMDAI evaluated 4 indices: stool frequency, rectal bleeding, PGA and endoscopy findings each on a scale of 0 to 3 with a maximum total score of 12. Rectal bleeding MMDAI subscore ranged from 0-3, where 0 = no blood seen, 1 = streaks of blood with stool less than half the time, 2 = obvious blood with stool most of the time, and 3 indicated blood alone passed. Missing data was imputed using LOCF method. | Week 6 | 
| Percentage of Participants Who Achieved >=3 Point Improvement From Baseline in the MMDAI Total Score Including Improvement of >=1 Point From Baseline in the MMDAI Rectal Bleeding Subscale Score and MMDAI Endoscopy Subscale at End of Week 6 | The MMDAI was used to assess the overall disease activity for each participant. The MMDAI evaluated 4 indices: stool frequency, rectal bleeding, PGA and endoscopy findings each on a scale of 0 to 3 with a maximum total score of 12. Rectal bleeding subscore ranged from 0-3, where 0 indicated no blood seen and 3 indicated blood alone passed. BF subscore ranged from 0-3, where 0 indicated normal number of stools per day and 3 indicated 5 or more stools than normal. PGA subscore ranged from 0-3, where 0 indicated normal and 3 indicated severe disease. Endoscopy subscore ranged from 0-3, where 0 indicated normal and 3 indicated severe disease. MMDAI total score ranged from 0-12, where higher score indicated severe disease. Missing data was imputed using LOCF method. | Week 6 | 
| Mean Change From Baseline to Week 6 in MMDAI Total Score and Subscale Scores | The MMDAI was used to assess the overall disease activity for each participant. The MMDAI evaluated 4 indices: stool frequency, rectal bleeding, PGA and endoscopy findings each on a scale of 0 to 3 with a maximum total score of 12. Rectal bleeding subscore ranged from 0-3, where 0 indicated no blood seen and 3 indicated blood alone passed. BF subscore ranged from 0-3, where 0 indicated normal number of stools per day and 3 indicated 5 or more stools than normal. PGA subscore ranged from 0-3, where 0 indicated normal and 3 indicated severe disease. Endoscopy subscore ranged from 0-3, where 0 indicated normal and 3 indicated severe disease. MMDAI total score ranged from 0-12, where higher score indicated severe disease. Missing data was imputed using LOCF method. | Baseline, Week 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Proctitis, Proctosigmoiditis, Ulcerative, Salix, Budesonide foam, Budesonide, Rectal, Gastrointestinal, Colitis, UC, UP, UPS, Additional relevant MeSH terms:, Proctocolitis, Ulcer, Colitis, Ulcerative, Gastroenteritis, Gastrointestinal Diseases, Digestive System Diseases, Rectal Diseases, Intestinal Diseases, Colonic Diseases, Sigmoid Diseases, Pathologic Processes, Inflammatory Bowel Diseases, Bronchodilator Agents, Autonomic Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Pharmacologic Actions, Anti-Asthmatic Agents, Respiratory System Agents, Therapeutic Uses, Glucocorticoids, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Anti-Inflammatory Agents