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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01008410

Enrollment

265

Registered

2009-11-05

Start date

2009-11-17

Completion date

2013-04-29

Last updated

2019-08-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Proctitis, Proctosigmoiditis

Keywords

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

Brief summary

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).

Interventions

DRUGBudesonide

Budesonide will be administered as per the dose and schedule specified in the respective arm.

DRUGPlacebo

Placebo matching to budesonide will be administered as per the schedule specified in the respective arm.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants Who Achieved Remission	Week 6	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).

Secondary

Measure	Time frame	Description
Number of Scheduled Assessments With Rectal Bleeding Responder Classification	Weeks 1, 2, 4, and 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. 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.
Percentage of Participants Who Achieved an Endoscopy MMDAI Subscale Score of 0 or 1 at End of Week 6	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.
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	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.
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	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.
Percentage of Participants Who Achieved a Rectal Bleeding MMDAI Subscale Score of 0 at End of Week 6	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.
Percentage of Participants Who Achieved Improvement of >=1 Point From Baseline in the MMDAI Rectal Bleeding Subscale Score at End of Week 6	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.
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	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.
Mean Change From Baseline to Week 6 in MMDAI Total Score and Subscale Scores	Baseline, 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.
Percentage of Participants Who Achieved Improvement of >=1 Point From Baseline in the MMDAI Endoscopy Subscale Score at End of Week 6	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Budesonide Participants who were diagnosed with active mild to moderate (UP or UPS, received 2 mg/25 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.	133
Placebo Participants who were diagnosed with active mild to moderate UP or UPS received 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.	132
Total	265

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	13	7
Overall Study	Lack of Efficacy	2	6
Overall Study	Lost to Follow-up	1	0
Overall Study	Low Cortisol	2	0
Overall Study	Met Exclusion Criterion	0	1
Overall Study	Noncompliance	1	0
Overall Study	Withdrawal by Subject	6	2

Baseline characteristics

Characteristic	Placebo	Total	Budesonide
Age, Continuous	41.4 years STANDARD_DEVIATION 13.24	42.4 years STANDARD_DEVIATION 13.6	43.2 years STANDARD_DEVIATION 13.94
Ethnicity (NIH/OMB) Hispanic or Latino	22 Participants	42 Participants	20 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	110 Participants	223 Participants	113 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants	2 Participants	0 Participants
Race (NIH/OMB) Asian	2 Participants	5 Participants	3 Participants
Race (NIH/OMB) Black or African American	5 Participants	20 Participants	15 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	123 Participants	238 Participants	115 Participants
Sex: Female, Male Female	80 Participants	152 Participants	72 Participants
Sex: Female, Male Male	52 Participants	113 Participants	61 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 134	0 / 131
other Total, other adverse events	66 / 134	47 / 131
serious Total, serious adverse events	2 / 134	3 / 131

Outcome results

Primary

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).

Time frame: Week 6

Population: ITT population included all randomized participants. Missing data was imputed using last observation carried forward (LOCF) method.

Arm	Measure	Value (NUMBER)
Budesonide	Percentage of Participants Who Achieved Remission	38.3 percentage of participants
Placebo	Percentage of Participants Who Achieved Remission	25.8 percentage of participants

Comparison: The logistic regression test was used to test for a difference in the percentages between the 2 treatment arms after adjusting for analysis center (country).p-value: 0.0324Regression, Logistic

Secondary

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.

Time frame: Baseline, Week 6