Randomized Placebo-Controlled Trial of Budesonide Multi-M... | NCT01532648

NCT01532648

Status Module

Label	Type	Description	Intervention Names
Budesonide MMX	Experimental	Participants will receive 1 oral tablet of budesonide MMX 9 mg for 56 days. Additionally, participants will continue to receive the same dose of their existing oral 5-ASA medication from their treating physician.	Drug: Budesonide MMX® Drug: 5-ASA
Placebo	Placebo Comparator	Participants will receive 1 oral tablet of matching budesonide MMX placebo for 56 days. Additionally, participants will continue to receive the same dose of their existing oral 5-ASA medication from their treating physician.	Drug: Placebo Drug: 5-ASA

Name	Type	Description	Arm Group Labels	Other Names
Budesonide MMX®	Drug	Oral tablet taken daily in the morning after breakfast.	Budesonide MMX

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants Who Achieved Clinical Remission at Day 56	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.	Baseline up to Day 56

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants of Who Achieved Clinical Response at Day 56	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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age 18 to 75 years, inclusive.
Established diagnosis of UC, based on clinical history, exclusion of infectious causes, and characteristic endoscopic and histologic findings.
Active mild or moderate UC with an ulcerative colitis disease activity index (UCDAI) score ≥4 and ≤10, with a mucosal appearance score of ≥1, and physician's rating of disease activity of 1 or 2.
Experiencing active UC (flare) despite a therapeutic dose of an oral 5-ASA (for example, mesalamine ≥2.4 g/day for ≥6 weeks prior to randomization, or equivalent). At screening, photographic evidence of active UC based on mucosal appearance must be obtained.
Women of childbearing potential or men of reproductive potential must be willing to use an acceptable form of contraception.
Able to comprehend the full nature and purpose of the study, including possible risks and side effects, and also able to comply with all requirements of the study. Must be able to understand and voluntarily sign an informed consent prior to any study procedures.

Exclusion Criteria:

Limited distal proctitis (from anal verge to 15 centimeters [cm] above the pectineal line).
Severe UC (UCDAI >10 or physician global assessment [PGA] >2), or non-active UC (UCDAI <4).
Infectious colitis or any recent history of infectious colitis (within 30 days of Screening).
Active malignancy or carcinoma in situ within the last 5 years (treated non-melanoma skin cancers are not exclusionary).
Active ulcer or bleeding disorder that may affect evaluation of blood in the stool.
Evidence or history of toxic megacolon or bowel resection.
Crohn's disease or indeterminate colitis.
Known hypersensitivity to budesonide or any ingredients of the budesonide MMX tablets.
Active tuberculosis or other active systemic or local bacterial, fungal, or viral infection.
Liver cirrhosis, evident hepatic or renal disease or insufficiency, or significant impairment of the biohumoral parameters (≥2.5*upper limit of normal [ULN] for alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, or ≥2*ULN for creatinine). Elevations in bilirubin due to benign conditions such as Gilbert's syndrome are not exclusionary.
Severe diseases in other organs or systems.
Local or systemic complications or other pathological states requiring therapy with corticosteroids and/or immunosuppressive agents.
Type 1 diabetes.
Glaucoma or with a family history of glaucoma in first-degree relatives.
Known hepatitis B, hepatitis C, or human immunodeficiency virus (HIV), according to the local privacy policy.
Severe anemia (<9 g/deciliter [dL] hemoglobin), leukopenia (<2.5*10^9 white blood cells [WBC]/liter [L]), or granulocytopenia (<1.2*10^9 cells/L).
Participants with a history of pancolitis (disease that extends to the hepatic flexure or beyond) for ≥8 years or left-sided colitis (disease confined to the left colon [that is, distal to the splenic flexure]) ≥15 years who have not yet completed a surveillance colonoscopy for dysplasia/colorectal cancer screening within the past year.
Prior budesonide MMX treatment.
Use of oral corticosteroids including other budesonide formulations within the last 4 weeks prior to randomization.
Use of any rectal 5-ASA or corticosteroid formulations within the last 2 weeks prior to randomization.
Use of immunosuppressive agents within the last 8 weeks prior to randomization.
Use of anti-tumor necrosis factor-alpha (TNFα) agents or other biologic therapies within the last 3 months prior to randomization.
Participation in experimental therapeutic studies within 30 days of randomization (or within the last 3 months if in an anti-TNFα or biologic agent study). Note: participants who participated in observational-only studies (and who did not receive study therapy) are not excluded.
Any other medical condition that, in the Principal Investigator's opinion, would make the administration of the study drug or study procedures hazardous to the participant or obscure the interpretation of adverse events (AEs) by the appropriate independent ethics committee/institutional review board.

Name	Affiliation	Role
Lindsey Mathew	Bausch Health Companies	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Santarus Clinical Investigational Site 1043		Anaheim	California	92801	United States
Santarus Clinical Investigational Site 1071

PubMed Identifier	Type	Citation	Retractions
28333362	Derived	Rubin DT, Cohen RD, Sandborn WJ, Lichtenstein GR, Axler J, Riddell RH, Zhu C, Barrett AC, Bortey E, Forbes WP. Budesonide Multimatrix Is Efficacious for Mesalamine-refractory, Mild to Moderate Ulcerative Colitis: A Randomised, Placebo-controlled Trial. J Crohns Colitis. 2017 Jul 1;11(7):785-791. doi: 10.1093/ecco-jcc/jjx032.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants Who Achieved Clinical Remission at Day 56

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.

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.

Posted

Count of Participants

Participants

Baseline up to Day 56

ID	Title	Description
OG000	Budesonide MMX	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.
OG001	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.

Units	Counts
Participants	OG000230 OG001228

Title

Denominators

Categories

Title	Measurements
	OG00056 OG00152

Secondary

Number of Participants of Who Achieved Clinical Response at Day 56

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.

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.

Posted

Count of Participants

Participants

Baseline up to Day 56

ID	Title	Description
OG000	Budesonide MMX	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.
OG001	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.

Secondary

Number of Participants Who Achieved UCDAI Remission at Day 56

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.

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.

Posted

Count of Participants

Participants

Baseline up to Day 56

ID	Title	Description
OG000	Budesonide MMX	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.
OG001	Placebo

Secondary

Number of Participants Who Achieved Endoscopic Remission at Day 56

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.

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.

Posted

Count of Participants

Participants

Screening and Day 56

ID	Title	Description
OG000	Budesonide MMX	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.
OG001	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.

Secondary

Number of Participants Who Achieved Histologic Healing at Day 56

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.

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.

Posted

Count of Participants

Participants

Baseline and Day 56

ID	Title	Description
OG000	Budesonide MMX	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.
OG001	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.

Units	Counts
Participants

Secondary

Number of Participants With Treatment Failure at Day 56

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.

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.

Posted

Count of Participants

Participants

Baseline up to Day 56

ID	Title	Description
OG000	Budesonide MMX	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.
OG001	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.

Secondary

Change From Baseline in Inflammatory Bowel Disease-Quality of Life (IBD-QoL) Questionnaire Scores

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.

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.

Posted

Mean

Standard Deviation

scores on a scale

Baseline, Days 14, 28, and 56

ID	Title	Description
OG000	Budesonide MMX	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.
OG001	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.

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Budesonide MMX	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.			10	255	14	255
EG001	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.			2	255	14	255

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Colitis ulcerative	Gastrointestinal disorders	MedDRA 11.0	Systematic Assessment	EG0006 affected255 at risk EG0011 affected255 at risk
Pancreatitis active	Gastrointestinal disorders	MedDRA 11.0	Systematic Assessment	EG0001 affected255 at risk EG0010 affected255 at risk
Anemia	Blood and lymphatic system disorders	MedDRA 11.0	Systematic Assessment	EG0001 affected255 at risk EG0010 affected255 at risk
Bronchitis	Infections and infestations	MedDRA 11.0	Systematic Assessment	EG0001 affected255 at risk EG0010 affected255 at risk
Hypokalemia	Metabolism and nutrition disorders	MedDRA 11.0	Systematic Assessment	EG0001 affected255 at risk EG0010 affected255 at risk
Type 2 diabetes mellitus	Metabolism and nutrition disorders	MedDRA 11.0	Systematic Assessment	EG0000 affected255 at risk EG0011 affected255 at risk

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Colitis ulcerative	Gastrointestinal disorders	MedDRA 11.0	Systematic Assessment		EG00011 affected255 at risk EG0019 affected255 at risk
Acne	Skin and subcutaneous tissue disorders	MedDRA 11.0	Systematic Assessment		EG0003 affected255 at risk EG0015 affected255 at risk

ID	Term
D003092	Colitis
D005759	Gastroenteritis
D005767	Gastrointestinal Diseases
D004066	Digestive System Diseases
D015212	Inflammatory Bowel Diseases
D003108	Colonic Diseases
D007410	Intestinal Diseases

ID	Title	Description
BG000	Budesonide MMX	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.
BG001	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.
BG002	Total	Total of all reporting groups