Ulcerative Colitis
Conditions
Keywords
ulcerative colitis, compliance, mesalamine, clinical study, clinical trial, clinical research, maintenance, long term, uc study, uc trial, uc research, open label, once a day, once, daily, daily dosing, simple, oral
Brief summary
To evaluate the percentage of subjects with clinical recurrence of UC at 6 months using MMX mesalamine once daily.
Interventions
DRUGMMX Mesalamine
MMX™ mesalamine 2.4g/day to 4.8g/day once-daily (QD) (two to four 1.2g tablets MMX™ mesalamine, dosed QD,respectively).
Sponsors
Shire
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
- Acute Phase: 1. Male and female subjects aged at least 18 years with active mild to moderate UC may enter the Acute Phase of the study. 2. Must have a previous diagnosis of UC confirmed by histology and endoscopy or radiology. 3. Males or non-pregnant, non-lactating FOCP who have a negative serum pregnancy test prior to entering the study and who are using adequate forms of contraception for the duration of the study. 4. General medical assessment must be satisfactory and there must not be clinically significant and relevant abnormalities. 5. Subject must have had \>2 acute episodes of UC (a documented episode of increased bowel frequency with rectal blood loss for which UC therapy was intensified) in their medical history. 6. Subjects who have relapsed on maintenance therapy after 2 weeks with doses of mesalamine at: a. \<2.0g/day, will be allowed into the Acute Phase at 2.4g/day QD, or b. between 2.0g/day - 3.0g/day will be allowed into the Acute Phase at 4.8g/day QD. Inclusion Criteria - Maintenance Phase: 1. Subjects determined to be quiescent at study entry on prior oral mesalamine therapy will be eligible to enter directly into the Maintenance Phase. 2. UC must have been considered to be quiescent, with scores of zero for both rectal bleeding and bowel movements.
Exclusion criteria
- Acute Phase: 1. Subjects who have been in relapse for \>6 weeks. 2. Female subjects who are pregnant or lactating, including females with a positive pregnancy test at screening. 3. Subjects must not have used another investigational agent within the last 30 days prior to enrollment. 4. Subjects who have unsuccessfully treated their current relapse with steroids or a mesalamine dose of \>2.0 g/day. 5. Subjects who have relapsed on maintenance therapy with doses of mesalamine \>2.0g/day. If the subject had a recent dose reduction from 2.0g/day to less than or equal to 2.0g/day and relapsed within 2 weeks of that dose reduction, the subject will not be eligible. 6. Subjects who have used systemic or rectal steroids within the last 4 weeks prior to Baseline, immunosuppressants within the last 6 weeks, antibiotic use within the last 7 days or chronic use of any anti-inflammatory drugs within 7 days prior to Baseline. 7. Subjects with hypersensitivity to salicylates/aspirin are excluded. 8. Subjects with moderate or severe hepatic impairment. 9. Subjects with Crohn's Disease, proctitis (where the extent of inflammation is less than or equal to 15cm), short bowel syndrome, bleeding disorders, or active peptic ulcer disease. 10. Subjects with asthma are excluded only if they are known to be mesalamine-sensitive. 11. Subjects with a positive stool culture for enteric pathogens (including Salmonella, Shigella, Yersinia, Aeromonas, Plesiomonas or Campylobacter) are excluded, as are those with C. difficile toxin present or with ova or parasites as detected by microscopy. 12. Subjects who have a history of previous colonic surgery. 13. Subjects with moderate or severe renal impairment are contra-indicated for treatment with mesalamine compounds and are excluded from the study. 14. Subjects with current or recurrent disease that could affect the colon, the action, absorption or disposition of the study drug, or clinical or laboratory assessments. 15. Subjects with current or relevant previous history of serious, severe or unstable (acute or progressive) physical or psychiatric illness, any medical disorder that may require treatment or make the patient unlikely to fully complete the study, or any condition that presents undue risk from the study drug or procedures. 16. Subjects with a history of alcohol or other substance abuse within the previous year. 17. Subjects who withdrew from a mesalamine trial due to a possibly or probably related severe AE or SAE are not eligible to enter this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Recurrence of Ulcerative Colitis (UC) During the Maintenance Phase at 6 Months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Recurrence of UC During the Maintenance Phase at 12 Months | 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. |
| Clinical Recurrence of UC During the Maintenance Phase Associated With Subject Compliance at 6 Months | 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. |
| Clinical Recurrence of UC During the Maintenance Phase Associated With Subject Compliance at 12 Months | 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. |
| Quiescent UC During the Maintenance Phase at 12 Months | 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). |
| Endoscopic Remission of UC During the Maintenance Phase at 12 Months | 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 \[ulceration; spontaneous bleeding\]. |
Countries
United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| MMX Mesalamine (Maintenance Phase) 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). | 208 |
| Total | 208 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Acute Phase | Consent withdrawn | 4 |
| Acute Phase | Lack of Efficacy | 64 |
| Acute Phase | Lost to Follow-up | 2 |
| Acute Phase | noncompliance | 1 |
| Acute Phase | Physician Decision | 1 |
| Acute Phase | Protocol Violation | 10 |
| Maintenance Phase | Adverse Event | 6 |
| Maintenance Phase | antibiotic use | 1 |
| Maintenance Phase | concomitant medication use | 1 |
| Maintenance Phase | Consent withdrawn | 5 |
| Maintenance Phase | hydrocodone use | 1 |
| Maintenance Phase | Lack of Efficacy | 40 |
| Maintenance Phase | Lost to Follow-up | 3 |
| Maintenance Phase | noncompliance | 2 |
| Maintenance Phase | Pregnancy | 1 |
| Maintenance Phase | prohibited medication use | 2 |
| Maintenance Phase | Protocol Violation | 7 |
| Maintenance Phase | study closure | 1 |
Baseline characteristics
| Characteristic | MMX Mesalamine (Maintenance Phase) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 23 Participants |
| Age, Categorical Between 18 and 65 years | 185 Participants |
| Age, Continuous | 46.9 years STANDARD_DEVIATION 13.7 |
| Region of Enrollment United States | 208 Participants |
| Sex: Female, Male Female | 108 Participants |
| Sex: Female, Male Male | 100 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 137 | 12 / 208 |
| serious Total, serious adverse events | 3 / 137 | 9 / 208 |
Outcome results
Primary
Clinical Recurrence of Ulcerative Colitis (UC) During the Maintenance Phase 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.
Time frame: 6 months
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MMX Mesalamine (Maintenance Phase) | Clinical Recurrence of Ulcerative Colitis (UC) During the Maintenance Phase at 6 Months | Yes | 46 participants |
| MMX Mesalamine (Maintenance Phase) | Clinical Recurrence of Ulcerative Colitis (UC) During the Maintenance Phase at 6 Months | No | 150 participants |
| MMX Mesalamine (Maintenance Phase) | Clinical Recurrence of Ulcerative Colitis (UC) During the Maintenance Phase at 6 Months | Missing | 11 participants |
Secondary
Clinical Recurrence of UC During the Maintenance Phase Associated With Subject Compliance 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.
Time frame: 12 months
Population: MPEP with non-missing data for clinical recurrence at 12 months.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MMX Mesalamine (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 |
| MMX Mesalamine (Maintenance Phase) | 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
Clinical Recurrence of UC During the Maintenance Phase Associated With Subject Compliance 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.
Time frame: 6 Months
Population: MPEP with non-missing data for clinical recurrence at 6 months.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MMX Mesalamine (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 |
| MMX Mesalamine (Maintenance Phase) | 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 |
| MMX Mesalamine (Maintenance Phase) | Clinical Recurrence of UC During the Maintenance Phase Associated With Subject Compliance at 6 Months | > 120% Compliant (n = 2) | 0 Percent of participants |
Secondary
Clinical Recurrence of UC During the Maintenance Phase 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.
Time frame: 12 Months
Population: MPEP
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MMX Mesalamine (Maintenance Phase) | Clinical Recurrence of UC During the Maintenance Phase at 12 Months | No | 125 participants |
| MMX Mesalamine (Maintenance Phase) | Clinical Recurrence of UC During the Maintenance Phase at 12 Months | Yes | 69 participants |
| MMX Mesalamine (Maintenance Phase) | Clinical Recurrence of UC During the Maintenance Phase at 12 Months | Missing | 13 participants |
Secondary
Endoscopic Remission of UC During the Maintenance Phase 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 \[ulceration; spontaneous bleeding\].
Time frame: 12 Months
Population: MPEP with non-missing data at 12 months.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MMX Mesalamine (Maintenance Phase) | Endoscopic Remission of UC During the Maintenance Phase at 12 Months | 124 Participants |
Secondary
Quiescent UC During the Maintenance Phase 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).
Time frame: 12 Months
Population: MPEP with non-missing data at 12 months.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MMX Mesalamine (Maintenance Phase) | Quiescent UC During the Maintenance Phase at 12 Months | 101 Participants |