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

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

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).

Study Overview

• Status: Completed
• Conditions: Proctitis; Proctosigmoiditis
• Intervention / Treatment: Drug: Budesonide; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 281
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Dothan, Alabama, United States
  • Arizona
    • Mesa, Arizona, United States
    • Tucson, Arizona, United States
  • Arkansas
    • Little Rock, Arkansas, United States
  • California
    • Chula Vista, California, United States
    • Garden Grove, California, United States
    • Mission Hills, California, United States
    • Monterey, California, United States
    • Roseville, California, United States
    • San Francisco, California, United States
  • Colorado
    • Lafayette, Colorado, United States
  • Connecticut
    • Bristol, Connecticut, United States
    • Hamden, Connecticut, United States
  • Florida
    • Altamonte Springs, Florida, United States
    • Cape Coral, Florida, United States
    • Hialeah, Florida, United States
    • North Miami Beach, Florida, United States
    • Winter Park, Florida, United States
  • Georgia
    • Macon, Georgia, United States
    • Marietta, Georgia, United States
    • Suwanee, Georgia, United States
  • Illinois
    • Moline, Illinois, United States
  • Iowa
    • Davenport, Iowa, United States
  • Kansas
    • Topeka, Kansas, United States
  • Louisiana
    • Metairie, Louisiana, United States
  • Maryland
    • Annapolis, Maryland, United States
    • Hagerstown, Maryland, United States
    • Prince Frederick, Maryland, United States
    • Silver Springs, Maryland, United States
  • Michigan
    • Chesterfield, Michigan, United States
    • Rochester, Michigan, United States
  • Mississippi
    • Tupelo, Mississippi, United States
  • Missouri
    • Saint Louis, Missouri, United States
  • New Jersey
    • Egg Harbor Township, New Jersey, United States
    • Marlton, New Jersey, United States
  • New York
    • Great Neck, New York, United States
    • Mineola, New York, United States
    • New York, New York, United States
    • North Massapequa, New York, United States
    • Stony Brook, New York, United States
  • North Carolina
    • Asheville, North Carolina, United States
    • Fayetteville, North Carolina, United States
    • Greensboro, North Carolina, United States
    • Jacksonville, North Carolina, United States
    • New Bern, North Carolina, United States
    • Raleigh, North Carolina, United States
    • Rocky Mount, North Carolina, United States
    • Wilmington, North Carolina, United States
  • Ohio
    • Beachwood, Ohio, United States
  • Oklahoma
    • Tulsa, Oklahoma, United States
  • Oregon
    • Portland, Oregon, United States
  • Tennessee
    • Germantown, Tennessee, United States
  • Texas
    • Houston, Texas, United States
    • La Porte, Texas, United States
    • Pasadena, Texas, United States
    • Plano, Texas, United States
    • San Antonio, Texas, United States
  • Utah
    • Ogden, Utah, United States
    • West Valley City, Utah, United States
  • Virginia
    • Chesapeake, Virginia, United States
    • Lynchburg, Virginia, United States
  • Wisconsin
    • Monroe, Wisconsin, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 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 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Budesonide; 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; Budesonide will be administered as per the dose and schedule specified in the respective arm.
Placebo Comparator: Placebo; 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; Placebo matching to budesonide will be administered as per the dose and schedule specified in the respective arm.

What is the study measuring?

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, 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 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 (BF) 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. 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, 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
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

Collaborators and Investigators

• Sponsor: Bausch Health Americas, Inc.
• Investigators: Study Director, Bausch health companies

Publications and helpful links

General Publications

• Bosworth BP, Sandborn WJ, Rubin DT, Harper JR. Baseline Oral 5-ASA Use and Efficacy and Safety of Budesonide Foam in Patients with Ulcerative Proctitis and Ulcerative Proctosigmoiditis: Analysis of 2 Phase 3 Studies. Inflamm Bowel Dis. 2016 Aug;22(8):1881-6. doi: 10.1097/MIB.0000000000000860.
• Sandborn WJ, Bosworth B, Zakko S, Gordon GL, Clemmons DR, Golden PL, Rolleri RL, Yu J, Barrett AC, Bortey E, Paterson C, Forbes WP. Budesonide foam induces remission in patients with mild to moderate ulcerative proctitis and ulcerative proctosigmoiditis. Gastroenterology. 2015 Apr;148(4):740-750.e2. doi: 10.1053/j.gastro.2015.01.037. Epub 2015 Jan 30.

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2009
• Primary Completion (Actual): March 18, 2013
• Study Completion (Actual): March 18, 2013

Study Registration Dates

• First Submitted: November 4, 2009
• First Submitted That Met QC Criteria: November 4, 2009
• First Posted (Estimate): November 5, 2009

Study Record Updates

• Last Update Posted (Actual): August 14, 2019
• Last Update Submitted That Met QC Criteria: July 19, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Additional relevant MeSH terms:; Pathologic Processes; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Glucocorticoids; Physiological Effects of Drugs; Inflammatory Bowel Diseases; Gastrointestinal; Colonic Diseases; Peripheral Nervous System Agents; Pharmacologic Actions; Colitis, Ulcerative; Therapeutic Uses; Colitis; Hormones; UC; Anti-Asthmatic Agents; Ulcer; Rectal Diseases; Anti-Inflammatory Agents; Bronchodilator Agents; Autonomic Agents; Respiratory System Agents; Budesonide; Rectal; Hormones, Hormone Substitutes, and Hormone Antagonists; Ulcerative; Proctitis; UP; Proctosigmoiditis; Salix; Budesonide foam; UPS; Proctocolitis; Sigmoid Diseases
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Colitis; Sigmoid Diseases; Ulcer; Proctitis; Proctocolitis; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Budesonide
• Other Study ID Numbers: BUCF3002