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Strategies in Maintenance for Patients Receiving Long-term Therapy (S.I.M.P.L.E.) With MMX (Multi-Matrix System) Mesalamine for Ulcerative Colitis (UC)

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ClinicalTrials.gov Identifier: NCT00446849
Recruitment Status : Completed
First Posted : March 13, 2007
Results First Posted : July 8, 2010
Last Update Posted : October 24, 2011
Sponsor:
Information provided by (Responsible Party):
Shire

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Ulcerative Colitis
Intervention Drug: MMX Mesalamine
Enrollment 290
Recruitment Details  
Pre-assignment Details A total of 290 subjects were enrolled in the study (138 in the acute phase and 152 that went directly into the maintenance phase). The 56 subjects that completed the acute phase entered the maintenance phase making a total of 208 subjects in the maintenance phase of the study.
Arm/Group Title Multi-Matrix System (MMX) Mesalamine
Hide Arm/Group Description Subjects whose ulcerative colitis (UC) was in flare at screening were enrolled in the 2-month acute phase (MMX Mesalamine dosed orally once-daily [QD] at 2.4-4.8 g/day), while those whose ulcerative colitis was quiescent at screening were enrolled directly into the 12-month maintenance phase (MMX Mesalamine dosed orally QD at 2.4 g/day). Subjects who were treated in the acute phase and attained quiescence were continued into the maintenance phase.
Period Title: Acute Phase
Started 138
Completed 56
Not Completed 82
Reason Not Completed
Lack of Efficacy             64
Protocol Violation             10
Consent withdrawn             4
Lost to Follow-up             2
Physician Decision             1
noncompliance             1
Period Title: Maintenance Phase
Started 208
Completed 138
Not Completed 70
Reason Not Completed
Lack of Efficacy             40
Protocol Violation             7
Adverse Event             6
Consent withdrawn             5
Lost to Follow-up             3
Pregnancy             1
noncompliance             2
prohibited medication use             2
antibiotic use             1
study closure             1
hydrocodone use             1
concomitant medication use             1
Arm/Group Title MMX Mesalamine (Maintenance Phase)
Hide Arm/Group Description Subjects whose ulcerative colitis was quiescent at screening were enrolled directly into the 12-month maintenance phase (MMX Mesalamine dosed orally QD at 2.4 g/day). Subjects who were treated in the acute phase and attained quiescence were continued into the maintenance phase. A total of 208 subjects entered the maintenance phase (152 whose UC was quiescent at screening + 56 whose UC was quiescent after the acute phase).
Overall Number of Baseline Participants 208
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 208 participants
<=18 years
0
   0.0%
Between 18 and 65 years
185
  88.9%
>=65 years
23
  11.1%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 208 participants
46.9  (13.70)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 208 participants
Female
108
  51.9%
Male
100
  48.1%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 208 participants
208
1.Primary Outcome
Title Clinical Recurrence of Ulcerative Colitis (UC) During the Maintenance Phase at 6 Months
Hide Description Clinical recurrence is defined as 4 or more bowel movements per day above the subject's normal frequency and associated with any of the following: urgency, abdominal pain, or rectal bleeding.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Maintenance phase efficacy population (MPEP) includes all subjects who, during the maintenance phase, took at least 1 dose of study medication and had at least 1 post-dose efficacy assessment.
Arm/Group Title MMX Mesalamine (Maintenance Phase)
Hide Arm/Group Description:
Subjects whose ulcerative colitis was in flare at screening were enrolled in the 2-month acute phase (MMX Mesalamine dosed QD at 2.4-4.8 g/day), while those whose ulcerative colitis was quiescent at screening were enrolled directly into the 12-month maintenance phase (MMX Mesalamine dosed QD at 2.4 g/day). Subjects who were treated in the acute phase and attained quiescence were continued into the maintenance phase.
Overall Number of Participants Analyzed 207
Measure Type: Number
Unit of Measure: participants
Yes 46
No 150
Missing 11
2.Secondary Outcome
Title Clinical Recurrence of UC During the Maintenance Phase at 12 Months
Hide Description Clinical recurrence is defined as 4 or more bowel movements per day above the subject's normal frequency and associated with any of the following: urgency, abdominal pain, or rectal bleeding.
Time Frame 12 Months
Hide Outcome Measure Data
Hide Analysis Population Description
MPEP
Arm/Group Title MMX Mesalamine (Maintenance Phase)
Hide Arm/Group Description:
Subjects whose ulcerative colitis was in flare at screening were enrolled in the 2-month acute phase (MMX Mesalamine dosed QD at 2.4-4.8 g/day), while those whose ulcerative colitis was quiescent at screening were enrolled directly into the 12-month maintenance phase (MMX Mesalamine dosed QD at 2.4 g/day). Subjects who were treated in the acute phase and attained quiescence were continued into the maintenance phase.
Overall Number of Participants Analyzed 207
Measure Type: Number
Unit of Measure: participants
Yes 69
No 125
Missing 13
3.Secondary Outcome
Title Clinical Recurrence of UC During the Maintenance Phase Associated With Subject Compliance at 6 Months
Hide Description Clinical recurrence is defined as 4 or more bowel movements per day above the subject's normal frequency and associated with any of the following: urgency, abdominal pain, or rectal bleeding. Compliance is a subject's adherence to a recommended course of treatment and for this study is calculated: [(Sum of days' supplies dispensed) divided by (Sum of days in all refill intervals)] x 100.
Time Frame 6 Months
Hide Outcome Measure Data
Hide Analysis Population Description
MPEP with non-missing data for clinical recurrence at 6 months.
Arm/Group Title MMX Mesalamine (Maintenance Phase)
Hide Arm/Group Description:
Subjects whose ulcerative colitis was in flare at screening were enrolled in the 2-month acute phase (MMX Mesalamine dosed QD at 2.4-4.8 g/day), while those whose ulcerative colitis was quiescent at screening were enrolled directly into the 12-month maintenance phase (MMX Mesalamine dosed QD at 2.4 g/day). Subjects who were treated in the acute phase and attained quiescence were continued into the maintenance phase.
Overall Number of Participants Analyzed 196
Measure Type: Number
Unit of Measure: Percent of participants
< 80% Compliant (n = 36) 36.1
80-120% Compliant (n = 158) 20.9
> 120% Compliant (n = 2) 0
4.Secondary Outcome
Title Clinical Recurrence of UC During the Maintenance Phase Associated With Subject Compliance at 12 Months
Hide Description Clinical recurrence is defined as 4 or more bowel movements per day above the subject's normal frequency and associated with any of the following: urgency, abdominal pain, or rectal bleeding. Compliance is a subject's adherence to a recommended course of treatment and for this study is calculated: (Sum of days' supplies dispensed) divided by (Sum of days in all refill intervals) x 100.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
MPEP with non-missing data for clinical recurrence at 12 months.
Arm/Group Title MMX Mesalamine (Maintenance Phase)
Hide Arm/Group Description:
Subjects whose ulcerative colitis was in flare at screening were enrolled in the 2-month acute phase (MMX Mesalamine dosed QD at 2.4-4.8 g/day), while those whose ulcerative colitis was quiescent at screening were enrolled directly into the 12-month maintenance phase (MMX Mesalamine dosed QD at 2.4 g/day). Subjects who were treated in the acute phase and attained quiescence were continued into the maintenance phase.
Overall Number of Participants Analyzed 194
Measure Type: Number
Unit of Measure: Percent of participants
< 80% Compliant (n = 40) 52.5
80-120% Compliant (n = 154) 31.2
5.Secondary Outcome
Title Quiescent UC During the Maintenance Phase at 12 Months
Hide Description Quiescent UC is defined as scores of 0 for both rectal bleeding and bowel movements. Rectal bleeding is assessed on a scale from 0-3 (0 = no rectal bleeding, 1 = streaks of blood, 2 = obvious blood, 3 = mostly blood). Bowel movements are assessed on a scale of 0-2 (0 = 0-1 more than normal per day, 1 = 2-3 more than normal per day, 2 = 4 or more than normal per day).
Time Frame 12 Months
Hide Outcome Measure Data
Hide Analysis Population Description
MPEP with non-missing data at 12 months.
Arm/Group Title MMX Mesalamine (Maintenance Phase)
Hide Arm/Group Description:
Subjects whose ulcerative colitis was in flare at screening were enrolled in the 2-month acute phase (MMX Mesalamine dosed QD at 2.4-4.8 g/day), while those whose ulcerative colitis was quiescent at screening were enrolled directly into the 12-month maintenance phase (MMX Mesalamine dosed QD at 2.4 g/day). Subjects who were treated in the acute phase and attained quiescence were continued into the maintenance phase.
Overall Number of Participants Analyzed 126
Measure Type: Number
Unit of Measure: Participants
101
6.Secondary Outcome
Title Endoscopic Remission of UC During the Maintenance Phase at 12 Months
Hide Description Endoscopic remission is defined as an endoscopy score of less than or equal to 1. Endoscopy score (mucosal appearance) ranges from 0-3 (0 = normal [intact vascular pattern; no friability or granulation], 1 = mild [erythema; decreased vascular pattern; minimal granularity], 2 = moderate [marked erythema; granularity; friability; absent vascular pattern; bleeding with minimal trauma; no ulcerations], 3 = severe [ulceration; spontaneous bleeding].
Time Frame 12 Months
Hide Outcome Measure Data
Hide Analysis Population Description
MPEP with non-missing data at 12 months.
Arm/Group Title MMX Mesalamine (Maintenance Phase)
Hide Arm/Group Description:
Subjects whose ulcerative colitis was in flare at screening were enrolled in the 2-month acute phase (MMX Mesalamine dosed QD at 2.4-4.8 g/day), while those whose ulcerative colitis was quiescent at screening were enrolled directly into the 12-month maintenance phase (MMX Mesalamine dosed QD at 2.4 g/day). Subjects who were treated in the acute phase and attained quiescence were continued into the maintenance phase.
Overall Number of Participants Analyzed 132
Measure Type: Number
Unit of Measure: Participants
124
Time Frame [Not Specified]
Adverse Event Reporting Description Safety population defined as all subjects who took at least one dose of study medication. In the acute phase 138 were randomized, but only 137 received at least one dose of study medication.
 
Arm/Group Title MMX Mesalamine (Acute Phase) MMX Mesalamine (Maintenance Phase)
Hide Arm/Group Description Subjects whose ulcerative colitis was in flare at screening were enrolled in the 2-month acute phase (MMX Mesalamine dosed QD at 2.4-4.8 g/day). Subjects whose ulcerative colitis was quiescent at screening were enrolled directly into the 12-month maintenance phase (MMX Mesalamine dosed QD at 2.4 g/day). Subjects who were treated in the acute phase and attained quiescence were continued into the maintenance phase.
All-Cause Mortality
MMX Mesalamine (Acute Phase) MMX Mesalamine (Maintenance Phase)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
MMX Mesalamine (Acute Phase) MMX Mesalamine (Maintenance Phase)
Affected / at Risk (%) Affected / at Risk (%)
Total   3/137 (2.19%)   9/208 (4.33%) 
Cardiac disorders     
Atrial fibrilation  1/137 (0.73%)  0/208 (0.00%) 
Angina unstable  0/137 (0.00%)  1/208 (0.48%) 
Gastrointestinal disorders     
Hematochezia  0/137 (0.00%)  1/208 (0.48%) 
Ileus  0/137 (0.00%)  1/208 (0.48%) 
Pancreatitis  0/137 (0.00%)  1/208 (0.48%) 
Hepatobiliary disorders     
Cholecystitis acute  0/137 (0.00%)  1/208 (0.48%) 
Infections and infestations     
Cellulitis  0/137 (0.00%)  1/208 (0.48%) 
Injury, poisoning and procedural complications     
Stent occlusion  1/137 (0.73%)  0/208 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain  0/137 (0.00%)  1/208 (0.48%) 
Nervous system disorders     
Headache  1/137 (0.73%)  0/208 (0.00%) 
Psychiatric disorders     
Schizophrenia  0/137 (0.00%)  1/208 (0.48%) 
Reproductive system and breast disorders     
Endometriosis  0/137 (0.00%)  1/208 (0.48%) 
Vascular disorders     
Hypertension  0/137 (0.00%)  1/208 (0.48%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
MMX Mesalamine (Acute Phase) MMX Mesalamine (Maintenance Phase)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/137 (0.00%)   12/208 (5.77%) 
Infections and infestations     
Sinusitis  0/137 (0.00%)  12/208 (5.77%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Results Point of Contact
Name/Title: Timothy Whitaker, M.D.
Organization: Shire Pharmaceutical
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT00446849     History of Changes
Other Study ID Numbers: SPD476-404
First Submitted: March 12, 2007
First Posted: March 13, 2007
Results First Submitted: April 9, 2010
Results First Posted: July 8, 2010
Last Update Posted: October 24, 2011