Ulcerative Colitis
Conditions
Brief summary
The overall objective of this study is to assess the safety and efficacy of high dose and low dose Asacol administered as 400 mg delayed-release tablets given every 12 hours for 6 weeks to children and adolescents with mildly-to-moderately active ulcerative colitis.
Interventions
DRUGAsacol 400 mg
High dose: 17-\<33 kg = 3 Asacol 400mg in morning and 2 Asacol 400 in PM, 33-\<54 kg = 5 Asacol 400mg in morning and 4 Asacol 400 in PM, 54-\<90 kg = 6 Asacol 400mg in morning and 6 Asacol 400 in PM
Sponsors
Warner Chilcott
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
5 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* are male or female between the ages of 5 and 17 years, inclusive, at the time of the first dose of study medication, with a history of biopsy and endoscopy confirmed UC; * have mildly-to-moderately active UC (either newly diagnosed or that has relapsed) as defined clinically by a Pediatric UC Activity Index (PUCAI) score 10 and 55, and, in the opinion of the Investigator, the patient does not require steroids; * have baseline scores of at least 1 for both rectal bleeding (Streaks of blood with stool less than half of the time) and stool frequency (1-2 stools greater than normal per day) as defined by the TM-Mayo Score
Exclusion criteria
* have UC known to be confined to the rectum (isolated rectal proctitis); * have a history of allergy or hypersensitivity to salicylates, aminosalicylates, or any component of the Asacol tablet; * have a significant co-existing illness or other condition(s), including but not limited to cancer or significant organic or psychiatric disease on medical history or physical examination, that, in the judgment of the Investigator, contraindicate(s) administration of the study drug and/or any study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Success PUCAI (Pediatric Ulcerative Colitis Activity Index), mITT/Modified Intent to Treat Population | Baseline and 6 weeks | PUCAI 0-85, abdominal pain (no pain/0, pain ignored/5, pain not ignored/10), rectal bleeding (none/0, small \<50% stool/10, small with most stools/20, large \>50% stool/30), stool consistency (formed/0, partially/5, unformed/10), # per 24 hrs (0-2/0, 3-5/5, 6-8/10, \>8/15), nocturnal bowel movements (no/0, yes/10), activity level (no limitation/0, occasional limitation/5, severely restricted/10) Remission \<10, Mild 10-34, Moderate 35-64, Severe 65-85, Success score\<10 at Wk 6 (complete) or reduction of \>=20 points baseline to Wk 6 with Wk 6 score\>=10 (partial) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Success PUCAI Amended Endpoint (5 Point Scale Abdominal Pain), mITT | Baseline and Week 6 | PUCAI 0-85, abdominal pain amended (no pain/0, very mild/2.5, mild/5, moderate/7.5, severe/10), rectal bleeding (none/0, small \<50% stool/10, small with most stools/20, large \>50% stool/30), stool consistency (formed/0, partially/5, unformed/10), # per 24 hrs (0-2/0, 3-5/5, 6-8/10, \>8/15), nocturnal bowel movements (no/0, yes/10), activity level (no limitation/0, occasional limitation/5, severely restricted/10) Remission \<10, Mild 10-34, Moderate 35-64, Severe 65-85, Success score\<10 at Wk 6 (complete) or reduction of \>=20 points baseline to Wk 6 with Wk 6 score\>=10 (partial) |
Countries
Canada, Croatia, Poland, Romania, United States
Participant flow
Recruitment details
Recruitment began 16 Dec 2008
Participants by arm
| Arm | Count |
|---|---|
| Low-Dose 17-\<33kg: AM - 2 Asacol 400mg & 1 placebo, PM - 1 Asacol 400mg & 1 placebo; 33-\<54kg: AM - 3 Asacol 400mg & 2 placebo, PM - 2 Asacol 400mg & 2 placebo; 54-\<90kg: AM & PM - 3 Asacol 400mg & 3 placebo | 41 |
| High-Dose 17-\<33kg: AM 3 Asacol 400mg, PM 2 Asacol 400mg; 33-\<54kg: AM5 Asacol 400mg, PM 4 Asacol 400mg; 54-\<90kg: AM & PM 6 Asacol 400mg | 42 |
| Total | 83 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 2 |
| Overall Study | Lack of Efficacy | 0 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Low-Dose | High-Dose | Total |
|---|---|---|---|
| Age Continuous | 13.0 years STANDARD_DEVIATION 3.2 | 12.8 years STANDARD_DEVIATION 3 | 12.9 years STANDARD_DEVIATION 3.1 |
| Age, Customized 5-8 years | 4 participants | 4 participants | 8 participants |
| Age, Customized 9-17 years | 37 participants | 38 participants | 75 participants |
| Region of Enrollment Canada | 0 participants | 4 participants | 4 participants |
| Region of Enrollment Croatia | 4 participants | 2 participants | 6 participants |
| Region of Enrollment Poland | 9 participants | 10 participants | 19 participants |
| Region of Enrollment Romania | 2 participants | 3 participants | 5 participants |
| Region of Enrollment United States | 26 participants | 23 participants | 49 participants |
| Sex: Female, Male Female | 22 Participants | 23 Participants | 45 Participants |
| Sex: Female, Male Male | 19 Participants | 19 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 20 / 50 | 15 / 41 |
| serious Total, serious adverse events | 5 / 41 | 2 / 41 |
Outcome results
Primary
Treatment Success PUCAI (Pediatric Ulcerative Colitis Activity Index), mITT/Modified Intent to Treat Population
PUCAI 0-85, abdominal pain (no pain/0, pain ignored/5, pain not ignored/10), rectal bleeding (none/0, small \<50% stool/10, small with most stools/20, large \>50% stool/30), stool consistency (formed/0, partially/5, unformed/10), # per 24 hrs (0-2/0, 3-5/5, 6-8/10, \>8/15), nocturnal bowel movements (no/0, yes/10), activity level (no limitation/0, occasional limitation/5, severely restricted/10) Remission \<10, Mild 10-34, Moderate 35-64, Severe 65-85, Success score\<10 at Wk 6 (complete) or reduction of \>=20 points baseline to Wk 6 with Wk 6 score\>=10 (partial)
Time frame: Baseline and 6 weeks
Population: miTT includes subjects who were randomized and took at least one dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose | Treatment Success PUCAI (Pediatric Ulcerative Colitis Activity Index), mITT/Modified Intent to Treat Population | 56.1 % participants with treatment success |
| High Dose | Treatment Success PUCAI (Pediatric Ulcerative Colitis Activity Index), mITT/Modified Intent to Treat Population | 55.0 % participants with treatment success |
Comparison: A total of about 100 subjects were to be enrolled in the study with the expectation that about 80 subjects (40/dose level) would complete. Minimum of 9 subjects in 5-8 year old range were to be enrolled, 4-5 per dose level (high/low). A 2-sided α=0.05 Fisher's Exact test has an estimated power of P=0.50 with 40 subjects per dose level.p-value: 0.92495% CI: [-22.7, 20.5]Cochran-Mantel-Haenszel
Secondary
Treatment Success PUCAI Amended Endpoint (5 Point Scale Abdominal Pain), mITT
PUCAI 0-85, abdominal pain amended (no pain/0, very mild/2.5, mild/5, moderate/7.5, severe/10), rectal bleeding (none/0, small \<50% stool/10, small with most stools/20, large \>50% stool/30), stool consistency (formed/0, partially/5, unformed/10), # per 24 hrs (0-2/0, 3-5/5, 6-8/10, \>8/15), nocturnal bowel movements (no/0, yes/10), activity level (no limitation/0, occasional limitation/5, severely restricted/10) Remission \<10, Mild 10-34, Moderate 35-64, Severe 65-85, Success score\<10 at Wk 6 (complete) or reduction of \>=20 points baseline to Wk 6 with Wk 6 score\>=10 (partial)
Time frame: Baseline and Week 6
Population: mITT subjects who were randomized \& took at least one dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose | Treatment Success PUCAI Amended Endpoint (5 Point Scale Abdominal Pain), mITT | 56.1 % participants with treatment success |
| High Dose | Treatment Success PUCAI Amended Endpoint (5 Point Scale Abdominal Pain), mITT | 57.5 % participants with treatment success |
Comparison: A total of about 100 subjects were to be enrolled in the study with the expectation that about 80 subjects (40/dose level) would complete. Minimum of 9 subjects in 5-8 year old range were to be enrolled, 4-5 per dose level (high/low). A 2-sided α=0.05 Fisher's Exact test has an estimated power of P=0.50 with 40 subjects per dose level.p-value: 0.819395% CI: [-20.2, 23]Cochran-Mantel-Haenszel