Ulcerative Colitis
Conditions
Brief summary
The purpose of this study is to evaluate the safety and efficacy of Asacol 4.8 g/day (800 mg tablet) versus Asacol 2.4 g/day (400 mg tablet
Detailed description
This study is designed to evaluate the safety and efficacy of 4.8 g/day using 800 mg Asacol tablets as compared to 2.4g/day using 400 mg Asacol tablets in newly- and previously-diagnosed patients who are experiencing a flare-up of mildly to moderately active ulcerative colitis.
Interventions
DRUGmesalamine
mesalamine 2.4 g/day (400 mg tablet) for 6 weeks
Sponsors
Warner Chilcott
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* confirmed diagnosis of ulcerative colitis
Exclusion criteria
* a history of allergy or hypersensitivity to salicylates or aminosalicylates; * a history of extensive small bowel resection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Classified as Treatment Success at Week 6, ITT Population | 6 weeks | Treatment Success - complete or partial response; Complete = complete resolution of clinical assessments (stool frequency, rectal bleeding, PFA \[patient's functional assessment\], sigmoidoscopy) and PGA (physician global assessment) = 0, Partial = improvement from baseline PGA score and improvement in at least 1 of the clinical assessments \[decrease of at least 1 on scale\] and no worsening \[no score increases\] of remaining clinical assessments. Each clinical assessment graded using scale 0/normal, better thru 3/severe, worse. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Physician's Global Assessment (PGA) Percentage of Patients Improved at Week 3, All Randomized Patients | Week 3 | PGA - 0-quiescent disease activity (all 0's) , 1-mild (mostly 1's), 2-moderate (mostly 2's), 3-severe (mostly 3's) based upon on scoring for stool frequency, rectal bleeding, PFR (patient's functional assessment - 0-well, 1-fair, 2-poor, 3-terrible), sigmoidoscopy findings. Improvement defined as either complete response (remission, score = 0) or partial response (improvement on treatment). Scoring Scale: 0-good thru 3-worse. |
| Physician's Global Assessment (PGA) Percentage of Patients Improved at Week 6, All Randomized Patients | Week 6 | PGA - 0-quiescent disease activity (all 0's) , 1-mild (mostly 1's), 2-moderate (mostly 2's), 3-severe (mostly 3's) based upon on scoring for stool frequency, rectal bleeding, PFR (patient's functional assessment - 0-well, 1-fair, 2-poor, 3-terrible), sigmoidoscopy findings. Improvement defined as complete response (remission, score = 0) or partial response (improvement on treatment). Scoring Scale: 0-good thru 3-worse. |
| Stool Frequency Improvement at Week 3, All Randomized Patients (Percentage) | Week 3 | 0: normal stool frequency per day, 1: 1-2 stools greater than normal per day, 2: 3-4 stools greater than normal per day, 3: 5 or more stools greater than normal per day, Scoring Scale: 0-good thru 3-worse. |
| Stool Frequency Improvement at Week 6, All Randomized Patients (Percentage) | Week 6 | 0: normal stool frequency per day, 1: 1-2 stools greater than normal per day, 2: 3-4 stools greater than normal per day, 3: 5 or more stools greater than normal per day, Scoring Scale: 0-good thru 3-worse. |
| Rectal Bleeding Improvement at Week 3, All Randomized Patients (Percentage) | Week 3 | 0: no blood seen, 1: streaks of blood with stool less than half of the time, 2: obvious blood with stool most of the time, 3: blood alone passed, Scoring Scale: 0-good thru 3-worse. |
| Percentage of Patients Classified as Treatment Success at Week 3, ITT Population | 3 weeks | Treatment Success - complete or partial response; Complete = complete resolution of clinical assessments (stool frequency, rectal bleeding, PFA \[patient's functional assessment\], sigmoidoscopy) and PGA (physician global assessment) = 0, Partial = improvement from baseline PGA score and improvement in at least 1 of the clinical assessments \[decrease of at least 1 on scale\] and no worsening \[no score increases\] of remaining clinical assessments. Each clinical assessment graded using scale 0/normal, better thru 3/severe, worse. |
| Improvement in Patient's Functional Assessment (PFA) at Week 3, All Randomized Patients (Percentage) | Week 3 | 0-generally well, 1-fair, 2-poor, 3-terrible |
| Improvement in Patient's Functional Assessment (PFA) at Week 6, All Randomized Patients (Percentage) | Week 6 | 0-generally well, 1-fair, 2-poor, 3-terrible |
| Improvement in Patient's Sigmoidoscopy Assessment Score at Week 3, All Randomized Patients (Percentage) | Week 3 | 0-normal (intact vascular pattern, no friability or granularity), 1-mild (erythema; diminished or absent vascular markings; mild granularity; friability), 2-moderate (marked erythema, granularity; absent vascular markings; bleeds with minimal trauma; no ulcerations), 3-severe (spontaneous bleeding, ulcerations). Scoring Scale: 0-good thru 3-worse. |
| Improvement in Patient's Sigmoidoscopy Assessment Score at Week 6, All Randomized Patients (Percentage) | Week 6 | 0-normal (intact vascular pattern, no friability or granularity), 1-mild (erythema; diminished or absent vascular markings; mild granularity; friability), 2-moderate (marked erythema, granularity; absent vascular markings; bleeds with minimal trauma; no ulcerations), 3-severe (spontaneous bleeding, ulcerations). Scoring Scale: 0-good thru 3-worse. |
| Rectal Bleeding Improvement at Week 6, All Randomized Patients (Percentage) | Week 6 | 0-no blood seen, 1- streaks of blood with stool less than half of the time, 2- obvious blood with stool most of the time, 3- blood alone passed. Scoring Scale: 0-good thru 3-worse. |
Countries
United States
Participant flow
Recruitment details
Screening began 9 Feb 2001
Participants by arm
| Arm | Count |
|---|---|
| Asacol 2.4 g/Day 2 - 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg Asacol tablet) 3 times daily for 6 weeks | 154 |
| Asacol 4.8 g/Day 2 - 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg tablet) 3 times daily for 6 weeks | 147 |
| Total | 301 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 5 |
| Overall Study | Lack of Efficacy | 8 | 7 |
| Overall Study | Physician Decision | 2 | 2 |
| Overall Study | Protocol Violation | 1 | 4 |
| Overall Study | Withdrawal by Subject | 2 | 6 |
Baseline characteristics
| Characteristic | Asacol 2.4 g/Day | Asacol 4.8 g/Day | Total |
|---|---|---|---|
| Age, Customized 18 - 64 years | 141 Participants | 133 Participants | 274 Participants |
| Age, Customized >= 65 years | 13 Participants | 14 Participants | 27 Participants |
| Race/Ethnicity, Customized Asian (Indian) | 2 Partcipants | 2 Partcipants | 4 Partcipants |
| Race/Ethnicity, Customized Asian (Oriental) | 1 Partcipants | 0 Partcipants | 1 Partcipants |
| Race/Ethnicity, Customized Black or African American | 18 Partcipants | 18 Partcipants | 36 Partcipants |
| Race/Ethnicity, Customized Caucasian | 122 Partcipants | 116 Partcipants | 238 Partcipants |
| Race/Ethnicity, Customized Hispanic | 10 Partcipants | 9 Partcipants | 19 Partcipants |
| Race/Ethnicity, Customized Multi-racial/other | 1 Partcipants | 2 Partcipants | 3 Partcipants |
| Sex: Female, Male Female | 79 Participants | 67 Participants | 146 Participants |
| Sex: Female, Male Male | 75 Participants | 80 Participants | 155 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 56 / 154 | 48 / 147 |
| serious Total, serious adverse events | 3 / 154 | 1 / 147 |
Outcome results
Primary
Percentage of Patients Classified as Treatment Success at Week 6, ITT Population
Treatment Success - complete or partial response; Complete = complete resolution of clinical assessments (stool frequency, rectal bleeding, PFA \[patient's functional assessment\], sigmoidoscopy) and PGA (physician global assessment) = 0, Partial = improvement from baseline PGA score and improvement in at least 1 of the clinical assessments \[decrease of at least 1 on scale\] and no worsening \[no score increases\] of remaining clinical assessments. Each clinical assessment graded using scale 0/normal, better thru 3/severe, worse.
Time frame: 6 weeks
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Asacol 2.4 g/Day | Percentage of Patients Classified as Treatment Success at Week 6, ITT Population | 51.3 Percentage of Participants |
| Asacol 4.8 g/Day | Percentage of Patients Classified as Treatment Success at Week 6, ITT Population | 55.9 Percentage of Participants |
Comparison: It was assumed that the true rate of improvement for the 2.4 g/day treatment group is 40% and for the 4.8 g/day group is 60%. To detect a true difference of 20% between these 2 groups with a 2-sided test, type I error of 0.05 (α = 0.05), and power of 90%, 140 patients were required per group to complete the study. To account for a 10% dropout/withdrawal rate, approximately 308 patients were to be enrolled in the study.p-value: 0.441195% CI: [-7.01, 16.11]Chi-squared
Secondary
Improvement in Patient's Functional Assessment (PFA) at Week 3, All Randomized Patients (Percentage)
0-generally well, 1-fair, 2-poor, 3-terrible
Time frame: Week 3
Population: All Randomized Patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Asacol 2.4 g/Day | Improvement in Patient's Functional Assessment (PFA) at Week 3, All Randomized Patients (Percentage) | 42.2 Percentage of Participants |
| Asacol 4.8 g/Day | Improvement in Patient's Functional Assessment (PFA) at Week 3, All Randomized Patients (Percentage) | 49.6 Percentage of Participants |
Comparison: It was assumed that the true rate of improvement for the 2.4 g/day treatment group is 40% and for the 4.8 g/day group is 60%. To detect a true difference of 20% between these 2 groups with a 2-sided test, type I error of 0.05 (α = 0.05), and power of 90%, 140 patients were required per group to complete the study. To account for a 10% dropout/withdrawal rate, approximately 308 patients were to be enrolled in the study.p-value: 0.230695% CI: [-4.66, 19.43]Chi-squared
Secondary
Improvement in Patient's Functional Assessment (PFA) at Week 6, All Randomized Patients (Percentage)
0-generally well, 1-fair, 2-poor, 3-terrible
Time frame: Week 6
Population: All Randomized Patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Asacol 2.4 g/Day | Improvement in Patient's Functional Assessment (PFA) at Week 6, All Randomized Patients (Percentage) | 54.1 Percentage of Participants |
| Asacol 4.8 g/Day | Improvement in Patient's Functional Assessment (PFA) at Week 6, All Randomized Patients (Percentage) | 60.7 Percentage of Participants |
Comparison: It was assumed that the true rate of improvement for the 2.4 g/day treatment group is 40% and for the 4.8 g/day group is 60%. To detect a true difference of 20% between these 2 groups with a 2-sided test, type I error of 0.05 (α = 0.05), and power of 90%, 140 patients were required per group to complete the study. To account for a 10% dropout/withdrawal rate, approximately 308 patients were to be enrolled in the study.p-value: 0.293195% CI: [-5.6, 18.64]Chi-squared
Secondary
Improvement in Patient's Sigmoidoscopy Assessment Score at Week 3, All Randomized Patients (Percentage)
0-normal (intact vascular pattern, no friability or granularity), 1-mild (erythema; diminished or absent vascular markings; mild granularity; friability), 2-moderate (marked erythema, granularity; absent vascular markings; bleeds with minimal trauma; no ulcerations), 3-severe (spontaneous bleeding, ulcerations). Scoring Scale: 0-good thru 3-worse.
Time frame: Week 3
Population: All Randomized Patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Asacol 2.4 g/Day | Improvement in Patient's Sigmoidoscopy Assessment Score at Week 3, All Randomized Patients (Percentage) | 51.5 Percentage of Participants |
| Asacol 4.8 g/Day | Improvement in Patient's Sigmoidoscopy Assessment Score at Week 3, All Randomized Patients (Percentage) | 52.0 Percentage of Participants |
Comparison: It was assumed that the true rate of improvement for the 2.4 g/day treatment group is 40% and for the 4.8 g/day group is 60%. To detect a true difference of 20% between these 2 groups with a 2-sided test, type I error of 0.05 (α = 0.05), and power of 90%, 140 patients were required per group to complete the study. To account for a 10% dropout/withdrawal rate, approximately 308 patients were to be enrolled in the study.p-value: 0.934995% CI: [-11.67, 12.69]Chi-squared
Secondary
Improvement in Patient's Sigmoidoscopy Assessment Score at Week 6, All Randomized Patients (Percentage)
0-normal (intact vascular pattern, no friability or granularity), 1-mild (erythema; diminished or absent vascular markings; mild granularity; friability), 2-moderate (marked erythema, granularity; absent vascular markings; bleeds with minimal trauma; no ulcerations), 3-severe (spontaneous bleeding, ulcerations). Scoring Scale: 0-good thru 3-worse.
Time frame: Week 6
Population: All Randomized Patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Asacol 2.4 g/Day | Improvement in Patient's Sigmoidoscopy Assessment Score at Week 6, All Randomized Patients (Percentage) | 66.7 Percentage of Participants |
| Asacol 4.8 g/Day | Improvement in Patient's Sigmoidoscopy Assessment Score at Week 6, All Randomized Patients (Percentage) | 73.2 Percentage of Participants |
Comparison: It was assumed that the true rate of improvement for the 2.4 g/day treatment group is 40% and for the 4.8 g/day group is 60%. To detect a true difference of 20% between these 2 groups with a 2-sided test, type I error of 0.05 (α = 0.05), and power of 90%, 140 patients were required per group to complete the study. To account for a 10% dropout/withdrawal rate, approximately 308 patients were to be enrolled in the study.p-value: 0.258395% CI: [-4.72, 17.73]Chi-squared
Secondary
Percentage of Patients Classified as Treatment Success at Week 3, ITT Population
Treatment Success - complete or partial response; Complete = complete resolution of clinical assessments (stool frequency, rectal bleeding, PFA \[patient's functional assessment\], sigmoidoscopy) and PGA (physician global assessment) = 0, Partial = improvement from baseline PGA score and improvement in at least 1 of the clinical assessments \[decrease of at least 1 on scale\] and no worsening \[no score increases\] of remaining clinical assessments. Each clinical assessment graded using scale 0/normal, better thru 3/severe, worse.
Time frame: 3 weeks
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Asacol 2.4 g/Day | Percentage of Patients Classified as Treatment Success at Week 3, ITT Population | 42.0 Percentage of Participants |
| Asacol 4.8 g/Day | Percentage of Patients Classified as Treatment Success at Week 3, ITT Population | 38.7 Percentage of Participants |
Comparison: It was assumed that the true rate of improvement for the 2.4 g/day treatment group is 40% and for the 4.8 g/day group is 60%. To detect a true difference of 20% between these 2 groups with a 2-sided test, type I error of 0.05 (α = 0.05), and power of 90%, 140 patients were required per group to complete the study. To account for a 10% dropout/withdrawal rate, approximately 308 patients were to be enrolled in the study.p-value: 0.567795% CI: [-14.67, 8.04]Chi-squared
Secondary
Physician's Global Assessment (PGA) Percentage of Patients Improved at Week 3, All Randomized Patients
PGA - 0-quiescent disease activity (all 0's) , 1-mild (mostly 1's), 2-moderate (mostly 2's), 3-severe (mostly 3's) based upon on scoring for stool frequency, rectal bleeding, PFR (patient's functional assessment - 0-well, 1-fair, 2-poor, 3-terrible), sigmoidoscopy findings. Improvement defined as either complete response (remission, score = 0) or partial response (improvement on treatment). Scoring Scale: 0-good thru 3-worse.
Time frame: Week 3
Population: All Randomized Patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Asacol 2.4 g/Day | Physician's Global Assessment (PGA) Percentage of Patients Improved at Week 3, All Randomized Patients | 49.3 Percentage of Participants |
| Asacol 4.8 g/Day | Physician's Global Assessment (PGA) Percentage of Patients Improved at Week 3, All Randomized Patients | 44.8 Percentage of Participants |
Comparison: It was assumed that the true rate of improvement for the 2.4 g/day treatment group is 40% and for the 4.8 g/day group is 60%. To detect a true difference of 20% between these 2 groups with a 2-sided test, type I error of 0.05 (α = 0.05), and power of 90%, 140 patients were required per group to complete the study. To account for a 10% dropout/withdrawal rate, approximately 308 patients were to be enrolled in the study.p-value: 0.47395% CI: [-16.6, 7.7]Chi-squared
Secondary
Physician's Global Assessment (PGA) Percentage of Patients Improved at Week 6, All Randomized Patients
PGA - 0-quiescent disease activity (all 0's) , 1-mild (mostly 1's), 2-moderate (mostly 2's), 3-severe (mostly 3's) based upon on scoring for stool frequency, rectal bleeding, PFR (patient's functional assessment - 0-well, 1-fair, 2-poor, 3-terrible), sigmoidoscopy findings. Improvement defined as complete response (remission, score = 0) or partial response (improvement on treatment). Scoring Scale: 0-good thru 3-worse.
Time frame: Week 6
Population: All Randomized Patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Asacol 2.4 g/Day | Physician's Global Assessment (PGA) Percentage of Patients Improved at Week 6, All Randomized Patients | 61.4 Percentage of Participants |
| Asacol 4.8 g/Day | Physician's Global Assessment (PGA) Percentage of Patients Improved at Week 6, All Randomized Patients | 64.8 Percentage of Participants |
Comparison: It was assumed that the true rate of improvement for the 2.4 g/day treatment group is 40% and for the 4.8 g/day group is 60%. To detect a true difference of 20% between these 2 groups with a 2-sided test, type I error of 0.05 (α = 0.05), and power of 90%, 140 patients were required per group to complete the study. To account for a 10% dropout/withdrawal rate, approximately 308 patients were to be enrolled in the study.p-value: 0.576195% CI: [-8.48, 15.26]Chi-squared
Secondary
Rectal Bleeding Improvement at Week 3, All Randomized Patients (Percentage)
0: no blood seen, 1: streaks of blood with stool less than half of the time, 2: obvious blood with stool most of the time, 3: blood alone passed, Scoring Scale: 0-good thru 3-worse.
Time frame: Week 3
Population: All Randomized Patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Asacol 2.4 g/Day | Rectal Bleeding Improvement at Week 3, All Randomized Patients (Percentage) | 48.1 Percentage of Participants |
| Asacol 4.8 g/Day | Rectal Bleeding Improvement at Week 3, All Randomized Patients (Percentage) | 59.1 Percentage of Participants |
Comparison: It was assumed that the true rate of improvement for the 2.4 g/day treatment group is 40% and for the 4.8 g/day group is 60%. To detect a true difference of 20% between these 2 groups with a 2-sided test, type I error of 0.05 (α = 0.05), and power of 90%, 140 patients were required per group to complete the study. To account for a 10% dropout/withdrawal rate, approximately 308 patients were to be enrolled in the study.p-value: 0.076995% CI: [-1.1, 22.91]Chi-squared
Secondary
Rectal Bleeding Improvement at Week 6, All Randomized Patients (Percentage)
0-no blood seen, 1- streaks of blood with stool less than half of the time, 2- obvious blood with stool most of the time, 3- blood alone passed. Scoring Scale: 0-good thru 3-worse.
Time frame: Week 6
Population: All Randomized Patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Asacol 2.4 g/Day | Rectal Bleeding Improvement at Week 6, All Randomized Patients (Percentage) | 60.2 Percentage of Participants |
| Asacol 4.8 g/Day | Rectal Bleeding Improvement at Week 6, All Randomized Patients (Percentage) | 71.5 Percentage of Participants |
Comparison: It was assumed that the true rate of improvement for the 2.4 g/day treatment group is 40% and for the 4.8 g/day group is 60%. To detect a true difference of 20% between these 2 groups with a 2-sided test, type I error of 0.05 (α = 0.05), and power of 90%, 140 patients were required per group to complete the study. To account for a 10% dropout/withdrawal rate, approximately 308 patients were to be enrolled in the study.p-value: 0.055195% CI: [-0.13, 22.92]Chi-squared
Secondary
Stool Frequency Improvement at Week 3, All Randomized Patients (Percentage)
0: normal stool frequency per day, 1: 1-2 stools greater than normal per day, 2: 3-4 stools greater than normal per day, 3: 5 or more stools greater than normal per day, Scoring Scale: 0-good thru 3-worse.
Time frame: Week 3
Population: All Randomized Patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Asacol 2.4 g/Day | Stool Frequency Improvement at Week 3, All Randomized Patients (Percentage) | 46.7 Percentage of Participants |
| Asacol 4.8 g/Day | Stool Frequency Improvement at Week 3, All Randomized Patients (Percentage) | 54.3 Percentage of Participants |
Comparison: It was assumed that the true rate of improvement for the 2.4 g/day treatment group is 40% and for the 4.8 g/day group is 60%. To detect a true difference of 20% between these 2 groups with a 2-sided test, type I error of 0.05 (α = 0.05), and power of 90%, 140 patients were required per group to complete the study. To account for a 10% dropout/withdrawal rate, approximately 308 patients were to be enrolled in the study.p-value: 0.21595% CI: [-4.41, 19.74]Chi-squared
Secondary
Stool Frequency Improvement at Week 6, All Randomized Patients (Percentage)
0: normal stool frequency per day, 1: 1-2 stools greater than normal per day, 2: 3-4 stools greater than normal per day, 3: 5 or more stools greater than normal per day, Scoring Scale: 0-good thru 3-worse.
Time frame: Week 6
Population: All Randomized Patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Asacol 2.4 g/Day | Stool Frequency Improvement at Week 6, All Randomized Patients (Percentage) | 63.2 Percentage of Participants |
| Asacol 4.8 g/Day | Stool Frequency Improvement at Week 6, All Randomized Patients (Percentage) | 66.7 Percentage of Participants |
Comparison: It was assumed that the true rate of improvement for the 2.4 g/day treatment group is 40% and for the 4.8 g/day group is 60%. To detect a true difference of 20% between these 2 groups with a 2-sided test, type I error of 0.05 (α = 0.05), and power of 90%, 140 patients were required per group to complete the study. To account for a 10% dropout/withdrawal rate, approximately 308 patients were to be enrolled in the study.p-value: 0.556995% CI: [-8.18, 15.2]Chi-squared