Ulcerative Colitis
Conditions
Brief summary
The purpose of this study is to compare the efficacy in maintaining remission of ulcerative colitis between a once daily (QD) Asacol regimen and a divided, twice daily (BID) Asacol dosing regimen.
Detailed description
Currently, in the US, Asacol therapy is indicated in divided doses for the maintenance of remission of ulcerative colitis at 1.6 g/day. A once daily dose is potentially beneficial to patients and physicians alike. This study will answer the following questions about once daily dosing: (1) does efficacy differ between once daily and twice daily dosing, (2) do patients prefer a once daily dosing regimen, and (3) is compliance better? This study will confirm whether there are benefits to once daily dosing beyond increased convenience. In order to understand how the QD regimen compares to BID in a real life practice setting, the patient will remain on the total daily dose of Asacol (1.6 g/day to 2.4 g/day) on which they were maintained in remission, but will be assigned to either a QD or BID regimen. This is an investigator-blinded study.
Interventions
DRUGMesalamine Once-Daily
Mesalamine tablets, 1.6-2.4 g/day taken orally once a day for 52 weeks
DRUGMesalamine Twice-Daily
Mesalamine tablets, 1.6-2.4 g/day, taken twice daily for 52 weeks
Sponsors
Warner Chilcott
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Documented history of ulcerative colitis that has been successfully maintained in remission for at least 3 months prior to study entry * At least one flare in the past 18 months * Utilizing a stable maintenance dose of oral Asacol of 1.6 g/day up to 2.4 g/day (stable dose is defined as the same dose for the past 3 months) * Females must be postmenopausal or surgically sterile or have a negative urine pregnancy test and practice acceptable contraception
Exclusion criteria
* History of or current renal disease * History of hepatic disease * History of allergy or hypersensitivity to salicylates, aminosalicylates * Treatment with immunomodulatory therapy, biologic therapy or corticosteroids within 90 days of screening * Received any antidiarrheals, antispasmodics, or antibiotic within 1 month of screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Remaining in Remission at Month 6, ITT Population, Determined by the Simple Clinical Colitis Activity Index (SCCAI) | 6 months | Remission defined as SCCAI \<5. Simple Clinical Colitis Activity Index: minimum score 0, maximum score 19, reflects disease activity over the 24 hours prior to completion. Composite Score: bowel frequency (day, 0-3) (night, 0-2), defecation urgency (0-3), blood in stool (0-3), general well being (0-4), extracolonic features (arthritis, pyoderma gangrenosum, erythema nodosum, uveitis - 1 per manifestation). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Remaining in Remission at Month 3, ITT Population | 3 months | Remission defined as SCCAI \< 5. Simple Clinical Colitis Activity Index: minimum score 0, maximum score 19, reflects disease activity over the 24 hours prior to completion. Composite Score: bowel frequency (day, 0-3) (night, 0-2), defecation urgency (0-3), blood in stool (0-3), general well being (0-4), extracolonic features (arthritis, pyoderma gangrenosum, erythema nodosum, uveitis - 1 per manifestation). |
| Percentage of Patients Remaining in Remission at Month 12, ITT Population | 12 months | Remission defined as SCCAI score \< 5. Simple Clinical Colitis Activity Index: minimum score 0, maximum score 19, reflects disease activity over the 24 hours prior to completion. Composite Score: bowel frequency (day, 0-3) (night, 0-2), defecation urgency (0-3), blood in stool (0-3), general well being (0-4), extracolonic features (arthritis, pyoderma gangrenosum, erythema nodosum, uveitis - 1 per manifestation). |
| Number of Subjects Who Relapse/Flare Within 6 Months, ITT Population | 6 months | Relapse/flare is defined as SCCAI \>= 5. Simple Clinical Colitis Activity Index: minimum score 0, maximum score 19, reflects disease activity over the 24 hours prior to completion. Composite Score: bowel frequency (day, 0-3) (night, 0-2), defecation urgency (0-3), blood in stool (0-3), general well being (0-4), extracolonic features (arthritis, pyoderma gangrenosum, erythema nodosum, uveitis - 1 per manifestation). |
| Total MARS (Medication Adherence Report Scale) Questionnaire Scores, ITT Population, Month 6 | 6 months | MARS: Composite score for the following statements: I change how many times per day I take my medicine, I forget to use it, I stop taking it for a while, I only use it when I am having active symptoms, I decide to miss out on a dose, I take less than instructed, I take more than instructed, I avoid using it if I can, I use it regularly every day (reverse scored): 5-never, 4-rarely, 3-sometimes, 2-often, 1-very often. Minimum score 9, maximum score 45. |
| Percentage of Participants Indicating Ulcerative Colitis in Remission (Patient Defined Remission Index), ITT Population, Month 6 | 6 months | Is your ulcerative colitis in remission (not active)? Y/N |
Countries
Canada, Puerto Rico, United States
Participant flow
Recruitment details
Enrollment began 9 Aug 2007
Participants by arm
| Arm | Count |
|---|---|
| Mesalamine Once-Daily an oral, once daily (QD) mesalamine regimen (1.6 - 2.4 g/day) | 514 |
| Mesalamine Twice-Daily an oral, twice daily (BID) mesalamine regimen (1.6 - 2.4 g/day) | 513 |
| Total | 1,027 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 7 |
| Overall Study | Lost to Follow-up | 17 | 23 |
| Overall Study | Physician Decision | 8 | 14 |
| Overall Study | Protocol Violation | 7 | 9 |
| Overall Study | Relapse | 65 | 65 |
| Overall Study | Took No Study Drug | 2 | 2 |
| Overall Study | Unable to Meet Protocol Criteria | 4 | 1 |
| Overall Study | Withdrawal by Subject | 29 | 14 |
Baseline characteristics
| Characteristic | Mesalamine Once-Daily | Mesalamine Twice-Daily | Total |
|---|---|---|---|
| Age, Customized < 65 years old | 409 Participants | 414 Participants | 823 Participants |
| Age, Customized > = 65 years old | 103 Participants | 97 Participants | 200 Participants |
| Gender Female | 261 participants | 268 participants | 529 participants |
| Gender Male | 251 participants | 243 participants | 494 participants |
| Region of Enrollment Canada | 6 participants | 8 participants | 14 participants |
| Region of Enrollment United States | 506 participants | 503 participants | 1009 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 512 | 0 / 511 |
| serious Total, serious adverse events | 18 / 512 | 9 / 511 |
Outcome results
Primary
Percentage of Patients Remaining in Remission at Month 6, ITT Population, Determined by the Simple Clinical Colitis Activity Index (SCCAI)
Remission defined as SCCAI \<5. Simple Clinical Colitis Activity Index: minimum score 0, maximum score 19, reflects disease activity over the 24 hours prior to completion. Composite Score: bowel frequency (day, 0-3) (night, 0-2), defecation urgency (0-3), blood in stool (0-3), general well being (0-4), extracolonic features (arthritis, pyoderma gangrenosum, erythema nodosum, uveitis - 1 per manifestation).
Time frame: 6 months
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mesalamine Once-Daily | Percentage of Patients Remaining in Remission at Month 6, ITT Population, Determined by the Simple Clinical Colitis Activity Index (SCCAI) | 90.5 Percentage of Participants |
| Mesalamine Twice-Daily | Percentage of Patients Remaining in Remission at Month 6, ITT Population, Determined by the Simple Clinical Colitis Activity Index (SCCAI) | 91.8 Percentage of Participants |
Comparison: Assumed true remission rate is 70% with no difference in remission rates between QD and BID dosing.The non-inferiority margin used in hypothesis testing was set to 10%.p-value: 0.501695% CI: [-2.3, 4.9]Cochran-Mantel-Haenszel
Secondary
Number of Subjects Who Relapse/Flare Within 6 Months, ITT Population
Relapse/flare is defined as SCCAI \>= 5. Simple Clinical Colitis Activity Index: minimum score 0, maximum score 19, reflects disease activity over the 24 hours prior to completion. Composite Score: bowel frequency (day, 0-3) (night, 0-2), defecation urgency (0-3), blood in stool (0-3), general well being (0-4), extracolonic features (arthritis, pyoderma gangrenosum, erythema nodosum, uveitis - 1 per manifestation).
Time frame: 6 months
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mesalamine Once-Daily | Number of Subjects Who Relapse/Flare Within 6 Months, ITT Population | 45 Participants |
| Mesalamine Twice-Daily | Number of Subjects Who Relapse/Flare Within 6 Months, ITT Population | 39 Participants |
p-value: 0.472695% CI: [0.762, 1.796]Log Rank
Secondary
Percentage of Participants Indicating Ulcerative Colitis in Remission (Patient Defined Remission Index), ITT Population, Month 6
Is your ulcerative colitis in remission (not active)? Y/N
Time frame: 6 months
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mesalamine Once-Daily | Percentage of Participants Indicating Ulcerative Colitis in Remission (Patient Defined Remission Index), ITT Population, Month 6 | 83.1 Percentage of Participants |
| Mesalamine Twice-Daily | Percentage of Participants Indicating Ulcerative Colitis in Remission (Patient Defined Remission Index), ITT Population, Month 6 | 86.6 Percentage of Participants |
Comparison: Assumed true remission rate is 70% with no difference in remission rates between QD and BID dosing.The non-inferiority margin used in hypothesis testing was set to 10%.p-value: 0.155795% CI: [-1.3, 8.5]Cochran-Mantel-Haenszel
Secondary
Percentage of Patients Remaining in Remission at Month 12, ITT Population
Remission defined as SCCAI score \< 5. Simple Clinical Colitis Activity Index: minimum score 0, maximum score 19, reflects disease activity over the 24 hours prior to completion. Composite Score: bowel frequency (day, 0-3) (night, 0-2), defecation urgency (0-3), blood in stool (0-3), general well being (0-4), extracolonic features (arthritis, pyoderma gangrenosum, erythema nodosum, uveitis - 1 per manifestation).
Time frame: 12 months
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mesalamine Once-Daily | Percentage of Patients Remaining in Remission at Month 12, ITT Population | 85.4 Percentage of Participants |
| Mesalamine Twice-Daily | Percentage of Patients Remaining in Remission at Month 12, ITT Population | 85.4 Percentage of Participants |
Comparison: Assumed true remission rate is 70% with no difference in remission rates between QD and BID dosing.The non-inferiority margin used in hypothesis testing was set to 10%.p-value: 0.97795% CI: [-4.6, 4.7]Cochran-Mantel-Haenszel
Secondary
Percentage of Patients Remaining in Remission at Month 3, ITT Population
Remission defined as SCCAI \< 5. Simple Clinical Colitis Activity Index: minimum score 0, maximum score 19, reflects disease activity over the 24 hours prior to completion. Composite Score: bowel frequency (day, 0-3) (night, 0-2), defecation urgency (0-3), blood in stool (0-3), general well being (0-4), extracolonic features (arthritis, pyoderma gangrenosum, erythema nodosum, uveitis - 1 per manifestation).
Time frame: 3 months
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mesalamine Once-Daily | Percentage of Patients Remaining in Remission at Month 3, ITT Population | 94.8 Percentage of Participants |
| Mesalamine Twice-Daily | Percentage of Patients Remaining in Remission at Month 3, ITT Population | 95.6 Percentage of Participants |
Comparison: Assumed true remission rate is 70% with no difference in remission rates between QD and BID dosing.The non-inferiority margin used in hypothesis testing was set to 10%.p-value: 0.542695% CI: [-1.8, 3.5]Cochran-Mantel-Haenszel
Secondary
Total MARS (Medication Adherence Report Scale) Questionnaire Scores, ITT Population, Month 6
MARS: Composite score for the following statements: I change how many times per day I take my medicine, I forget to use it, I stop taking it for a while, I only use it when I am having active symptoms, I decide to miss out on a dose, I take less than instructed, I take more than instructed, I avoid using it if I can, I use it regularly every day (reverse scored): 5-never, 4-rarely, 3-sometimes, 2-often, 1-very often. Minimum score 9, maximum score 45.
Time frame: 6 months
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mesalamine Once-Daily | Total MARS (Medication Adherence Report Scale) Questionnaire Scores, ITT Population, Month 6 | 42.3 MARS Score | Standard Error 0.23 |
| Mesalamine Twice-Daily | Total MARS (Medication Adherence Report Scale) Questionnaire Scores, ITT Population, Month 6 | 41.8 MARS Score | Standard Error 0.24 |
p-value: 0.175395% CI: [-1.09, 0.2]ANOVA