Trial Outcomes & Findings for Randomized Placebo-Controlled Trial of Budesonide Multi-Matrix System (MMX®) 9 Milligrams (mg) in Participants With Ulcerative Colitis Currently on a 5-Aminosalicylic Acid (5-ASA) (NCT NCT01532648)

Results Overview

Clinical remission defined as a score of 0 for rectal bleeding and 0 for stool frequency components from the Ulcerative Colitis Disease Activity Index (UCDAI). UCDAI is the sum (0 to 12) of 4 severity scores (0 to 3). Stool frequency and rectal bleeding were based on information recorded in daily participant diaries. The diary entries were averaged for rectal bleeding and stool frequency for 3 days prior to (and closest to) Day 56 with non-missing diary data, within 5 days prior to (and closest to) Day 56. The 5 days did not include any days of the flexible sigmoidoscopy (or colonoscopy) or the preparation for the flexible sigmoidoscopy (or colonoscopy). These averages were rounded to integer values. If either subscore could not be calculated because of missing data, the score for that UCDAI component was set to missing. Participants with insufficient data at Day 56 were excluded from the analysis. Participants who had clinical remission at Baseline were classified as non-responders.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

510 participants

Primary outcome timeframe

Baseline up to Day 56

Results posted on

2019-09-06

Participant Flow

Participant milestones

Participant milestones
Measure	Budesonide MMX Participants received 1 oral tablet of budesonide multi-matrix system (MMX) 9 milligrams (mg) for 56 days. Additionally, participants continued to receive the same dose of their existing oral 5-aminosalicylic acid (5-ASA) medication from their treating physician.	Placebo Participants received 1 oral tablet of matching budesonide MMX placebo for 56 days. Additionally, participants continued to receive the same dose of their existing oral 5-ASA medication from their treating physician.
Overall Study STARTED	255	255
Overall Study Safety Population	255	255
Overall Study Intent-To-Treat Population	230	228
Overall Study COMPLETED	219	238
Overall Study NOT COMPLETED	36	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Budesonide MMX Participants received 1 oral tablet of budesonide multi-matrix system (MMX) 9 milligrams (mg) for 56 days. Additionally, participants continued to receive the same dose of their existing oral 5-aminosalicylic acid (5-ASA) medication from their treating physician.	Placebo Participants received 1 oral tablet of matching budesonide MMX placebo for 56 days. Additionally, participants continued to receive the same dose of their existing oral 5-ASA medication from their treating physician.
Overall Study Lost to Follow-up	3	4
Overall Study Lack of Efficacy	4	1
Overall Study Protocol Violation	1	1
Overall Study Adverse Event	12	9
Overall Study Withdrawal by Subject	16	2

Baseline Characteristics

Randomized Placebo-Controlled Trial of Budesonide Multi-Matrix System (MMX®) 9 Milligrams (mg) in Participants With Ulcerative Colitis Currently on a 5-Aminosalicylic Acid (5-ASA)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Budesonide MMX n=255 Participants Participants received 1 oral tablet of budesonide MMX 9 mg for 56 days. Additionally, participants continued to receive the same dose of their existing oral 5-ASA medication from their treating physician.	Placebo n=255 Participants Participants received 1 oral tablet of matching budesonide MMX placebo for 56 days. Additionally, participants continued to receive the same dose of their existing oral 5-ASA medication from their treating physician.	Total n=510 Participants Total of all reporting groups
Age, Continuous	44.5 years STANDARD_DEVIATION 13.86 • n=5 Participants	44.9 years STANDARD_DEVIATION 13.44 • n=7 Participants	44.7 years STANDARD_DEVIATION 13.64 • n=5 Participants
Sex: Female, Male Female	122 Participants n=5 Participants	108 Participants n=7 Participants	230 Participants n=5 Participants
Sex: Female, Male Male	133 Participants n=5 Participants	147 Participants n=7 Participants	280 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to Day 56

Population: Participants who received at least 1 dose of study drug and had active ulcerative colitis (UC) at study entry as a cause of their symptoms (Intent-To-Treat Population \[ITT\]) with evaluable clinical remission data.

Clinical remission defined as a score of 0 for rectal bleeding and 0 for stool frequency components from the Ulcerative Colitis Disease Activity Index (UCDAI). UCDAI is the sum (0 to 12) of 4 severity scores (0 to 3). Stool frequency and rectal bleeding were based on information recorded in daily participant diaries. The diary entries were averaged for rectal bleeding and stool frequency for 3 days prior to (and closest to) Day 56 with non-missing diary data, within 5 days prior to (and closest to) Day 56. The 5 days did not include any days of the flexible sigmoidoscopy (or colonoscopy) or the preparation for the flexible sigmoidoscopy (or colonoscopy). These averages were rounded to integer values. If either subscore could not be calculated because of missing data, the score for that UCDAI component was set to missing. Participants with insufficient data at Day 56 were excluded from the analysis. Participants who had clinical remission at Baseline were classified as non-responders.

Outcome measures

Outcome measures
Measure	Budesonide MMX n=230 Participants Participants received 1 oral tablet of budesonide MMX 9 mg for 56 days. Additionally, participants continued to receive the same dose of their existing oral 5-ASA medication from their treating physician.	Placebo n=228 Participants Participants received 1 oral tablet of matching budesonide MMX placebo for 56 days. Additionally, participants continued to receive the same dose of their existing oral 5-ASA medication from their treating physician.
Number of Participants Who Achieved Clinical Remission at Day 56	56 Participants	52 Participants

SECONDARY outcome

Timeframe: Baseline up to Day 56

Population: Participants who received at least 1 dose of study drug and had active UC at study entry as a cause of their symptoms (ITT Population) with evaluable clinical response data.

Clinical response defined as an improvement in UCDAI from Baseline of ≥3 points with a rectal bleeding score ≤1. UCDAI is the sum (0 to 12) of 4 severity scores (0 to 3). Rectal bleeding was based on information recorded in daily participant diaries. The diary entries were averaged for rectal bleeding for 3 days prior to (and closest to) Day 56 with non-missing diary data, within 5 days prior to (and closest to) Day 56. The 5 days did not include any days of the flexible sigmoidoscopy (or colonoscopy) or the preparation for the flexible sigmoidoscopy (or colonoscopy). These averages were rounded to integer values. If either subscore could not be calculated because of missing data, the score for that UCDAI component was set to missing. Participants with insufficient data at Day 56 were excluded from the analysis.

Outcome measures

Outcome measures
Measure	Budesonide MMX n=230 Participants Participants received 1 oral tablet of budesonide MMX 9 mg for 56 days. Additionally, participants continued to receive the same dose of their existing oral 5-ASA medication from their treating physician.	Placebo n=228 Participants Participants received 1 oral tablet of matching budesonide MMX placebo for 56 days. Additionally, participants continued to receive the same dose of their existing oral 5-ASA medication from their treating physician.
Number of Participants of Who Achieved Clinical Response at Day 56	101 Participants	86 Participants

SECONDARY outcome

Timeframe: Baseline up to Day 56

Population: Participants who received at least 1 dose of study drug and had active UC at study entry as a cause of their symptoms (ITT Population) with evaluable UCDAI remission data.

UCDAI remission was defined as a total UCDAI score ≤1 with subscores of 0 for rectal bleeding, stool frequency, and mucosal appearance of the colon. UCDAI is the sum (0 to 12) of 4 severity scores (0 to 3). Stool frequency and rectal bleeding were based on information recorded in daily participant diaries and mucosal appearance was based on endoscopy results. The diary entries were averaged for rectal bleeding and stool frequency for 3 days prior to (and closest to) Day 56 with non-missing diary data, within 5 days prior to (and closest to) Day 56. The 5 days did not include any days of the flexible sigmoidoscopy (or colonoscopy) or the preparation for the flexible sigmoidoscopy (or colonoscopy). These averages were rounded to integer values. If the subscore could not be calculated because of missing data, the score for that UCDAI component was set to missing. Participants with insufficient data at Day 56 were excluded from the analysis.

Outcome measures

Outcome measures
Measure	Budesonide MMX n=230 Participants Participants received 1 oral tablet of budesonide MMX 9 mg for 56 days. Additionally, participants continued to receive the same dose of their existing oral 5-ASA medication from their treating physician.	Placebo n=228 Participants Participants received 1 oral tablet of matching budesonide MMX placebo for 56 days. Additionally, participants continued to receive the same dose of their existing oral 5-ASA medication from their treating physician.
Number of Participants Who Achieved UCDAI Remission at Day 56	30 Participants	17 Participants

SECONDARY outcome

Timeframe: Screening and Day 56

Population: Participants who received at least 1 dose of study drug and had active UC at study entry as a cause of their symptoms (ITT Population) with evaluable endoscopic response data.

Endoscopic remission was defined as a score of 0 in the mucosal appearance component subscore of the UCDAI at Day 56. UCDAI is the sum (0 to 12) of 4 severity scores (0 to 3). Mucosal appearance was based on endoscopy results. If the mucosal appearance subscore could not be calculated because of missing data, endoscopic remission was set to missing. Participants with insufficient data at Day 56 were excluded from the analysis.

Outcome measures

Outcome measures
Measure	Budesonide MMX n=230 Participants Participants received 1 oral tablet of budesonide MMX 9 mg for 56 days. Additionally, participants continued to receive the same dose of their existing oral 5-ASA medication from their treating physician.	Placebo n=228 Participants Participants received 1 oral tablet of matching budesonide MMX placebo for 56 days. Additionally, participants continued to receive the same dose of their existing oral 5-ASA medication from their treating physician.
Number of Participants Who Achieved Endoscopic Remission at Day 56	46 Participants	28 Participants

SECONDARY outcome

Timeframe: Baseline and Day 56

Population: Participants who received at least 1 dose of study drug and had active UC at study entry as a cause of their symptoms (ITT Population) with evaluable histologic healing data.

Participants achieved histologic healing if histologic assessments of all biopsy specimens were graded as 0 (normal mucosa). If the score for ≥1 sample was missing, the overall score at that visit was set to missing. Participants with insufficient data at Day 56 were excluded from analysis.

Outcome measures

Outcome measures
Measure	Budesonide MMX n=230 Participants Participants received 1 oral tablet of budesonide MMX 9 mg for 56 days. Additionally, participants continued to receive the same dose of their existing oral 5-ASA medication from their treating physician.	Placebo n=228 Participants Participants received 1 oral tablet of matching budesonide MMX placebo for 56 days. Additionally, participants continued to receive the same dose of their existing oral 5-ASA medication from their treating physician.
Number of Participants Who Achieved Histologic Healing at Day 56	62 Participants	40 Participants

SECONDARY outcome

Timeframe: Baseline up to Day 56

Population: Participants who received at least 1 dose of study drug and had active UC at study entry as a cause of their symptoms (ITT Population) with evaluable UCDAI data.

Treatment failure was defined as an unchanged, worsened, or missing UCDAI score at Day 56. UCDAI is the sum (0 to 12) of 4 severity scores (0 to 3). Stool frequency and rectal bleeding was based on information recorded in daily participant diaries and mucosal appearance was based on endoscopy results. The diary entries were averaged for rectal bleeding and stool frequency for 3 days prior to (and closest to) Day 56 with non-missing diary data, within 5 days prior to (and closest to) Day 56. The 5 days did not include any days of the flexible sigmoidoscopy (or colonoscopy) or the preparation for the flexible sigmoidoscopy (or colonoscopy). These averages were rounded to integer values. If the subscore could not be calculated because of missing data, the score for that UCDAI component was set to missing. Participants with insufficient data at Day 56 were excluded from the analysis.

Outcome measures

Outcome measures
Measure	Budesonide MMX n=230 Participants Participants received 1 oral tablet of budesonide MMX 9 mg for 56 days. Additionally, participants continued to receive the same dose of their existing oral 5-ASA medication from their treating physician.	Placebo n=228 Participants Participants received 1 oral tablet of matching budesonide MMX placebo for 56 days. Additionally, participants continued to receive the same dose of their existing oral 5-ASA medication from their treating physician.
Number of Participants With Treatment Failure at Day 56	45 Participants	61 Participants

SECONDARY outcome

Timeframe: Baseline, Days 14, 28, and 56

Population: Participants who received at least 1 dose of study drug and had active UC at study entry as a cause of their symptoms (ITT Population) with evaluable IBD-QoL data.

The IBD-QoL questionnaire was self-completed by the participant. The IBD-QoL is a disease-specific instrument to evaluate the quality of life of participants with UC. This 32-item questionnaire has 4 dimensions: bowel function, emotional function, systemic symptoms, and social function. The total score is presented, which ranges from 32 to 224, with higher scores indicating a better quality of life. The scores of participants in remission usually range from 170 to 190. If \>50% of the questionnaire answers for a particular dimension were missing, this dimension score was set to missing. The total score for the IBD-QoL was the sum of the domain scores, however, if any dimension score was missing, the total IBD-QoL score was set to missing.

Outcome measures

Outcome measures
Measure	Budesonide MMX n=230 Participants Participants received 1 oral tablet of budesonide MMX 9 mg for 56 days. Additionally, participants continued to receive the same dose of their existing oral 5-ASA medication from their treating physician.	Placebo n=228 Participants Participants received 1 oral tablet of matching budesonide MMX placebo for 56 days. Additionally, participants continued to receive the same dose of their existing oral 5-ASA medication from their treating physician.
Change From Baseline in Inflammatory Bowel Disease-Quality of Life (IBD-QoL) Questionnaire Scores Baseline	132.8 scores on a scale Standard Deviation 31.36	134.1 scores on a scale Standard Deviation 32.48
Change From Baseline in Inflammatory Bowel Disease-Quality of Life (IBD-QoL) Questionnaire Scores Change at Day 14	24.4 scores on a scale Standard Deviation 27.45	21.3 scores on a scale Standard Deviation 29.20
Change From Baseline in Inflammatory Bowel Disease-Quality of Life (IBD-QoL) Questionnaire Scores Change at Day 28	31.8 scores on a scale Standard Deviation 33.38	25.7 scores on a scale Standard Deviation 33.16
Change From Baseline in Inflammatory Bowel Disease-Quality of Life (IBD-QoL) Questionnaire Scores Change at Day 56	31.1 scores on a scale Standard Deviation 38.73	31.7 scores on a scale Standard Deviation 37.02

Adverse Events

Budesonide MMX

Serious events: 10 serious events

Other events: 14 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Budesonide MMX n=255 participants at risk Participants received 1 oral tablet of budesonide MMX 9 mg for 56 days. Additionally, participants continued to receive the same dose of their existing oral 5-ASA medication from their treating physician.	Placebo n=255 participants at risk Participants received 1 oral tablet of matching budesonide MMX placebo for 56 days. Additionally, participants continued to receive the same dose of their existing oral 5-ASA medication from their treating physician.
Blood and lymphatic system disorders Anemia	0.39% 1/255 • Baseline up to Day 85 All randomized participants who received at least 1 dose of study drug (Safety Population).	0.00% 0/255 • Baseline up to Day 85 All randomized participants who received at least 1 dose of study drug (Safety Population).
Infections and infestations Bronchitis	0.39% 1/255 • Baseline up to Day 85 All randomized participants who received at least 1 dose of study drug (Safety Population).	0.00% 0/255 • Baseline up to Day 85 All randomized participants who received at least 1 dose of study drug (Safety Population).
Metabolism and nutrition disorders Hypokalemia	0.39% 1/255 • Baseline up to Day 85 All randomized participants who received at least 1 dose of study drug (Safety Population).	0.00% 0/255 • Baseline up to Day 85 All randomized participants who received at least 1 dose of study drug (Safety Population).
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.00% 0/255 • Baseline up to Day 85 All randomized participants who received at least 1 dose of study drug (Safety Population).	0.39% 1/255 • Baseline up to Day 85 All randomized participants who received at least 1 dose of study drug (Safety Population).
Gastrointestinal disorders Colitis ulcerative	2.4% 6/255 • Baseline up to Day 85 All randomized participants who received at least 1 dose of study drug (Safety Population).	0.39% 1/255 • Baseline up to Day 85 All randomized participants who received at least 1 dose of study drug (Safety Population).
Gastrointestinal disorders Pancreatitis active	0.39% 1/255 • Baseline up to Day 85 All randomized participants who received at least 1 dose of study drug (Safety Population).	0.00% 0/255 • Baseline up to Day 85 All randomized participants who received at least 1 dose of study drug (Safety Population).

Other adverse events

Other adverse events
Measure	Budesonide MMX n=255 participants at risk Participants received 1 oral tablet of budesonide MMX 9 mg for 56 days. Additionally, participants continued to receive the same dose of their existing oral 5-ASA medication from their treating physician.	Placebo n=255 participants at risk Participants received 1 oral tablet of matching budesonide MMX placebo for 56 days. Additionally, participants continued to receive the same dose of their existing oral 5-ASA medication from their treating physician.
Gastrointestinal disorders Colitis ulcerative	4.3% 11/255 • Baseline up to Day 85 All randomized participants who received at least 1 dose of study drug (Safety Population).	3.5% 9/255 • Baseline up to Day 85 All randomized participants who received at least 1 dose of study drug (Safety Population).
Skin and subcutaneous tissue disorders Acne	1.2% 3/255 • Baseline up to Day 85 All randomized participants who received at least 1 dose of study drug (Safety Population).	2.0% 5/255 • Baseline up to Day 85 All randomized participants who received at least 1 dose of study drug (Safety Population).

Additional Information

Director of Clinical Operations

Bausch Health Americas, Inc

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Please contact Sponsor directly for additional information.
Publication restrictions are in place

Restriction type: OTHER