Trial Outcomes & Findings for 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) (NCT NCT00446849)
NCT ID: NCT00446849
Last Updated: 2021-06-14
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
290 participants
Primary outcome timeframe
6 months
Results posted on
2021-06-14
Participant Flow
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.
Participant milestones
| Measure |
Multi-Matrix System (MMX) Mesalamine
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.
|
|---|---|
|
Acute Phase
STARTED
|
138
|
|
Acute Phase
COMPLETED
|
56
|
|
Acute Phase
NOT COMPLETED
|
82
|
|
Maintenance Phase
STARTED
|
208
|
|
Maintenance Phase
COMPLETED
|
138
|
|
Maintenance Phase
NOT COMPLETED
|
70
|
Reasons for withdrawal
| Measure |
Multi-Matrix System (MMX) Mesalamine
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.
|
|---|---|
|
Acute Phase
Lack of Efficacy
|
64
|
|
Acute Phase
Protocol Violation
|
10
|
|
Acute Phase
Consent withdrawn
|
4
|
|
Acute Phase
Lost to Follow-up
|
2
|
|
Acute Phase
Physician Decision
|
1
|
|
Acute Phase
noncompliance
|
1
|
|
Maintenance Phase
Lack of Efficacy
|
40
|
|
Maintenance Phase
Protocol Violation
|
7
|
|
Maintenance Phase
Adverse Event
|
6
|
|
Maintenance Phase
Consent withdrawn
|
5
|
|
Maintenance Phase
Lost to Follow-up
|
3
|
|
Maintenance Phase
Pregnancy
|
1
|
|
Maintenance Phase
noncompliance
|
2
|
|
Maintenance Phase
prohibited medication use
|
2
|
|
Maintenance Phase
antibiotic use
|
1
|
|
Maintenance Phase
study closure
|
1
|
|
Maintenance Phase
hydrocodone use
|
1
|
|
Maintenance Phase
concomitant medication use
|
1
|
Baseline Characteristics
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)
Baseline characteristics by cohort
| Measure |
MMX Mesalamine (Maintenance Phase)
n=208 Participants
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).
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
185 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
23 Participants
n=5 Participants
|
|
Age, Continuous
|
46.9 years
STANDARD_DEVIATION 13.70 • n=5 Participants
|
|
Sex: Female, Male
Female
|
108 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
100 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
208 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 6 monthsPopulation: 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.
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.
Outcome measures
| Measure |
MMX Mesalamine (Maintenance Phase)
n=207 Participants
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.
|
|---|---|
|
Clinical Recurrence of Ulcerative Colitis (UC) During the Maintenance Phase at 6 Months
Yes
|
46 participants
|
|
Clinical Recurrence of Ulcerative Colitis (UC) During the Maintenance Phase at 6 Months
No
|
150 participants
|
|
Clinical Recurrence of Ulcerative Colitis (UC) During the Maintenance Phase at 6 Months
Missing
|
11 participants
|
SECONDARY outcome
Timeframe: 12 MonthsPopulation: MPEP
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.
Outcome measures
| Measure |
MMX Mesalamine (Maintenance Phase)
n=207 Participants
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.
|
|---|---|
|
Clinical Recurrence of UC During the Maintenance Phase at 12 Months
No
|
125 participants
|
|
Clinical Recurrence of UC During the Maintenance Phase at 12 Months
Missing
|
13 participants
|
|
Clinical Recurrence of UC During the Maintenance Phase at 12 Months
Yes
|
69 participants
|
SECONDARY outcome
Timeframe: 6 MonthsPopulation: MPEP with non-missing data for clinical recurrence at 6 months.
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.
Outcome measures
| Measure |
MMX Mesalamine (Maintenance Phase)
n=196 Participants
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.
|
|---|---|
|
Clinical Recurrence of UC During the Maintenance Phase Associated With Subject Compliance at 6 Months
< 80% Compliant (n = 36)
|
36.1 Percent of participants
|
|
Clinical Recurrence of UC During the Maintenance Phase Associated With Subject Compliance at 6 Months
80-120% Compliant (n = 158)
|
20.9 Percent of participants
|
|
Clinical Recurrence of UC During the Maintenance Phase Associated With Subject Compliance at 6 Months
> 120% Compliant (n = 2)
|
0 Percent of participants
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: MPEP with non-missing data for clinical recurrence at 12 months.
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.
Outcome measures
| Measure |
MMX Mesalamine (Maintenance Phase)
n=194 Participants
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.
|
|---|---|
|
Clinical Recurrence of UC During the Maintenance Phase Associated With Subject Compliance at 12 Months
< 80% Compliant (n = 40)
|
52.5 Percent of participants
|
|
Clinical Recurrence of UC During the Maintenance Phase Associated With Subject Compliance at 12 Months
80-120% Compliant (n = 154)
|
31.2 Percent of participants
|
SECONDARY outcome
Timeframe: 12 MonthsPopulation: MPEP with non-missing data at 12 months.
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).
Outcome measures
| Measure |
MMX Mesalamine (Maintenance Phase)
n=126 Participants
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.
|
|---|---|
|
Quiescent UC During the Maintenance Phase at 12 Months
|
101 Participants
|
SECONDARY outcome
Timeframe: 12 MonthsPopulation: MPEP with non-missing data at 12 months.
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 \[ulceration; spontaneous bleeding\].
Outcome measures
| Measure |
MMX Mesalamine (Maintenance Phase)
n=132 Participants
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.
|
|---|---|
|
Endoscopic Remission of UC During the Maintenance Phase at 12 Months
|
124 Participants
|
Adverse Events
MMX Mesalamine (Acute Phase)
Serious events: 3 serious events
Other events: 0 other events
Deaths: 0 deaths
MMX Mesalamine (Maintenance Phase)
Serious events: 9 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
MMX Mesalamine (Acute Phase)
n=137 participants at risk
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).
|
MMX Mesalamine (Maintenance Phase)
n=208 participants at risk
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.
|
|---|---|---|
|
Cardiac disorders
Atrial fibrilation
|
0.73%
1/137
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.
|
0.00%
0/208
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.
|
|
Injury, poisoning and procedural complications
Stent occlusion
|
0.73%
1/137
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.
|
0.00%
0/208
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.
|
|
Nervous system disorders
Headache
|
0.73%
1/137
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.
|
0.00%
0/208
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.
|
|
Cardiac disorders
Angina unstable
|
0.00%
0/137
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.
|
0.48%
1/208
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.
|
|
Gastrointestinal disorders
Hematochezia
|
0.00%
0/137
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.
|
0.48%
1/208
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.
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/137
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.
|
0.48%
1/208
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.
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/137
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.
|
0.48%
1/208
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.
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/137
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.
|
0.48%
1/208
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.
|
|
Infections and infestations
Cellulitis
|
0.00%
0/137
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.
|
0.48%
1/208
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.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/137
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.
|
0.48%
1/208
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.
|
|
Psychiatric disorders
Schizophrenia
|
0.00%
0/137
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.
|
0.48%
1/208
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.
|
|
Reproductive system and breast disorders
Endometriosis
|
0.00%
0/137
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.
|
0.48%
1/208
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.
|
|
Vascular disorders
Hypertension
|
0.00%
0/137
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.
|
0.48%
1/208
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.
|
Other adverse events
| Measure |
MMX Mesalamine (Acute Phase)
n=137 participants at risk
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).
|
MMX Mesalamine (Maintenance Phase)
n=208 participants at risk
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.
|
|---|---|---|
|
Infections and infestations
Sinusitis
|
0.00%
0/137
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.
|
5.8%
12/208
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.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER