Clinical Trial Results:
A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Oral Budesonide MMX® 9 mg Extended-release Tablets as Add-on Therapy in Patients with Active, Mild or Moderate Ulcerative Colitis not Adequately Controlled on a Background Oral 5-ASA Regimen
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Summary
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EudraCT number |
2011-005115-82 |
Trial protocol |
HU CZ PL BG EE LV LT |
Global end of trial date |
02 Oct 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Jan 2020
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First version publication date |
01 Jan 2020
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
C2011-0401
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01532648 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Salix Pharmaceuticals, Inc
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Sponsor organisation address |
400 Somerset Corporate Blvd, Bridgewater, United States, 08807
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Public contact |
Director of Clinical Operations, Salix Pharmaceuticals, Inc, 011 908-927-0873, Lindsey.Mathew@bauschhealth.com
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Scientific contact |
Director of Clinical Operations, Salix Pharmaceuticals, Inc, 011 908-927-0873, Lindsey.Mathew@bauschhealth.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
02 Oct 2013
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
02 Oct 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
02 Oct 2013
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of this study was to compare the efficacy of budesonide multi-matrix system (MMX) 9 milligrams (mg) and placebo as add-on therapy to an existing oral 5-aminosalicylic acid (5-ASA) regimen for the induction of clinical remission in participants with active, mild to moderate ulcerative colitis (UC) when administered for 8 weeks.
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Protection of trial subjects |
This study was conducted in accordance with the Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects, and with Good Clinical Practice (GCP), as required by the US Code of Federal Regulations applicable to clinical studies (21 CFR Parts 11, 50, 54, 56
and 312, 42 USC 282(j), International Council for Harmonisation, Harmonised Tripartite Guideline
E6(R1): GCP and E2A: Safety Data Management, and applicable local regulations.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
27 Jan 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 115
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Country: Number of subjects enrolled |
Canada: 35
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Country: Number of subjects enrolled |
Czech Republic: 38
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Country: Number of subjects enrolled |
Bulgaria: 48
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Country: Number of subjects enrolled |
Hungary: 33
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Country: Number of subjects enrolled |
Poland: 49
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Country: Number of subjects enrolled |
Ukraine: 54
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Country: Number of subjects enrolled |
Estonia: 17
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Country: Number of subjects enrolled |
Latvia: 27
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Country: Number of subjects enrolled |
Lithuania: 19
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Country: Number of subjects enrolled |
Russian Federation: 75
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Worldwide total number of subjects |
510
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EEA total number of subjects |
231
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
477
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From 65 to 84 years |
33
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85 years and over |
0
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Recruitment
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Recruitment details |
- | |||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
At Screening and Visit 5 (Day 56), participants were required to undergo a flexible sigmoidoscopy (or colonoscopy, if clinically indicated) with 1 photograph and 3 mucosal biopsies taken from the most severely affected region(s) of the colon visualized during the endoscopy procedure. | |||||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Carer, Assessor | |||||||||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Budesonide MMX | |||||||||||||||||||||||||||||||||
Arm description |
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. | |||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Budesonide MMX®
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Investigational medicinal product code |
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Other name |
Budesonide Multi-Matrix System
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Budesonide MMX was administered as per the dose and schedule specified in the respective arms.
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Arm title
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Placebo | |||||||||||||||||||||||||||||||||
Arm description |
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. | |||||||||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Budesonide MMX matching placebo was administered as per the dose and schedule specified in the respective arms.
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| Notes [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: The number of subjects who started is the same as the number of subjects in the arm (N=255). |
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Baseline characteristics reporting groups
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Reporting group title |
Budesonide MMX
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Reporting group description |
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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Budesonide MMX (ITT Population)
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
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.
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Subject analysis set title |
Placebo (ITT Population)
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
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.
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End points reporting groups
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Reporting group title |
Budesonide MMX
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Reporting group description |
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. | ||
Reporting group title |
Placebo
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Reporting group description |
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. | ||
Subject analysis set title |
Budesonide MMX (ITT Population)
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
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.
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Subject analysis set title |
Placebo (ITT Population)
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
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.
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End point title |
Number of Participants Who Achieved Clinical Remission at Day 56 | |||||||||
End point description |
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. 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 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 who had clinical remission at Baseline were classified as non-responders. Population included participants who received at least 1 dose of study drug and had active UC at study entry as a cause of their symptoms (Intent-to-Treat [ITT] Population) with evaluable clinical remission data.
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End point type |
Primary
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End point timeframe |
Baseline up to Day 56
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Statistical analysis title |
Chi square test | |||||||||
Comparison groups |
Budesonide MMX (ITT Population) v Placebo (ITT Population)
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Number of subjects included in analysis |
400
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.4877 | |||||||||
Method |
Chi-squared | |||||||||
Confidence interval |
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End point title |
Number of Participants of Who Achieved Clinical Response at Day 56 | |||||||||
End point description |
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). The 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. Population included 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.
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End point type |
Secondary
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End point timeframe |
Baseline up to Day 56
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Participants Who Achieved UCDAI Remission at Day 56 | |||||||||
End point description |
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 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. Population included 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.
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End point type |
Secondary
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End point timeframe |
Baseline up to Day 56
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Participants Who Achieved Endoscopic Remission at Day 56 | |||||||||
End point description |
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. Population included 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.
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End point type |
Secondary
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End point timeframe |
Screening and Day 56
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Participants Who Achieved Histologic Healing at Day 56 | |||||||||
End point description |
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. Population included 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.
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End point type |
Secondary
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End point timeframe |
Baseline and Day 56
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Participants with Treatment Failure at Day 56 | |||||||||
End point description |
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. 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.
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End point type |
Secondary
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End point timeframe |
Baseline up to Day 56
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| No statistical analyses for this end point | ||||||||||
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End point title |
Change From Baseline in Inflammatory Bowel Disease-Quality of Life (IBD-QoL) Questionnaire Scores | ||||||||||||||||||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline, Days 14, 28, and 56
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Baseline up to Day 85
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Adverse event reporting additional description |
All randomized participants who received at least 1 dose of study drug (Safety Population).
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
11.0
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Reporting groups
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Reporting group title |
Budesonide MMX
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Reporting group description |
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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 2% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
