Ulcerative Colitis
Conditions
Brief summary
The purpose of this study is to determine whether low dose Asacol® (27 mg/kg - 71 mg/kg) and high dose Asacol® (53 mg/kg - 118 mg/kg) are safe and effective when dosed as 400 mg delayed-release tablets given twice daily for 26 weeks to children and adolescents for the maintenance of remission of ulcerative colitis.
Interventions
DRUGAsacol 400 mg
17-33kg = 3 Asacol 400mg AM & 2 Asacol 400mg PM; 33-\<54kg = 5 Asacol 400 mg AM & 4 Asacol 400mg PM; 54-\<90kg = 6 Asacol 400mg AM & PM
Sponsors
Warner Chilcott
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
5 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* male or female between the ages of 5 and 17 years, inclusive, at the time of the first dose of study medication; * have a documented history of UC that has been successfully maintained in complete remission for at least 1 month prior to study entry * have a baseline PUCAI score \< 10 * have a body weight no less than 17 kg and no more than 90 kg * have a history of at least 1 active episode or relapse in the last 12 months * have taken a stable maintenance dose of oral mesalamine (or equivalent oral 5-ASA dose) for at least 1 month prior to entry in the study. Stable is defined as the same dose for the last month. * maintained complete remission, as defined, throughout the 30-day run-in phase. Note:ONLY applies to those patients who complete the 6-week treatment in complete remission from Study 2007017 and immediately roll-over to the 30-day run-in phase * are female patients who are pre-menarchal or have a negative urine pregnancy test and, if sexually active, practice acceptable contraception (e.g., abstinence; oral, intramuscular, or implanted hormonal contraception \[at least 3 months prior to enrollment\]
Exclusion criteria
* 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 * have a history or presence of any condition causing malabsorption or an effect on gastrointestinal motility or history of extensive small bowel resection (greater than one half the length of the small intestine) causing short bowel syndrome * any condition causing malabsorption or an effect on gastrointestinal motility * have current renal disease, or a screening blood urea nitrogen (BUN) or creatinine value that is \> 1.5 times the upper limit of the age appropriate normal * have a documented history of or current hepatic disease, or liver function tests (alanine transaminase \[ALT\], aspartate transaminase \[AST\], total bilirubin) that are \> 2 times the upper limit of normal * have a history of pancreatitis * have undergone treatment with any oral, intravenous, intramuscular, or rectally administered corticosteroids (including budesonide) within 30 days prior to the Screening visit * have undergone treatment with any rectal mesalamine therapy within 30 days prior to the screening visit * have undergone treatment with immunomodulatory therapy including, but not limited to: rosiglitazone, 6-mercaptopurine or azathioprine, cyclosporine, or methotrexate within 90 days prior to Screening visit * have undergone treatment with biologic therapy including, but not limited to: infliximab,adalimumab, certolizumab or other biologic treatment of ulcerative colitis within 90 days prior to Screening visit * have undergone treatment with antibiotics (other than topical antibiotics) including metronidazole within 7 days prior to the Screening visit * have undergone treatment with aspirin or other nonsteroidal anti-inflammatory drugs NSAIDs) within 7 days prior to the Screening visit * have undergone treatment with any antidiarrheals and/or antispasmodics within 30 days of the Screening visit * have a stool examination positive for Clostridium difficile (C. difficile), bacterial pathogens, or ova and parasites. Note: Because normal gut flora may vary by geography, the Medical Monitor should be consulted before excluding a patient with a stool sample that is positive for C. difficile, bacterial pathogens or ova and parasites.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Success PUCAI (Pediatric Ulcerative Colitis Activity Index), mITT/Modified Intent to Treat Population | Week 26 | PUCAI Score (0-85, sum of scores for each): abdominal pain (0/5/10 - no pain/ignored/not ignored), rectal bleeding (0/10/20/30 - none, small amount \<50% of stools, small amount most stools, large amount \>50%), stool consistency (0/5/10 - formed, partially formed, completely formed), # stools/24 hrs. (0/5/10/15 - 0-2/3-5/6-8/\>8), nocturnal bowel/any diarrhea causing wakening (0/10 - no/yes), activity level (0/5/10 - no limitation/occ limitation, severe restrictions). Remission \<10, Mild 10-34, Moderate 35-64, Severe 65-85. Remission defined as Treatment Success. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Success PUCAI Amended Endpoint (5 Point Scale Abdominal Pain), mITT | Week 26 | PUCAI Score (0-85, sum of scores for each) abdominal pain (0/2.5/5/7.5/10 - no pain/very mild/mild/moderate/severe), rectal bleeding (0/10/20/30 - none, small amount \<50% of stools, small amount most stools, large amount \>50%), stool consistency (0/5/10 - formed, partially formed, completely formed), # stools/24 hrs. (0/5/10/15 - 0-2/3-5/6-8/\>8), nocturnal bowel/any diarrhea causing wakening (0/10 - no/yes), activity level (0/5/10 - no limitation/occ limitation, severe restrictions). Remission \<10, Mild 10-34, Moderate 35-64, Severe 65-85. Remission is Treatment Success. |
Countries
Canada, Croatia, Poland, Romania, Russia, United States
Participant flow
Recruitment details
Screening began on 6 Oct 2009
Pre-assignment details
There was a 30-day run-in phase for subjects continuing directly from Study 2007017.
Participants by arm
| Arm | Count |
|---|---|
| High Dose Subjects who weigh 17-\<33 kg will receive 2.0 g/day Asacol. Subjects who weigh 33-\<54 kg will receive 3.6 g/day Asacol. Subjects who weigh 54-\<90 kg will receive 4.8 g/day Asacol. | 19 |
| Low Dose Subjects who weigh 17-\<33 kg will receive 1.2 g/day Asacol. Subjects who weigh 33-\<54 kg will receive 2.0 g/day Asacol. Subjects who weigh 54-\<90 kg will receive 2.4 g/day Asacol. | 20 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Lack of Efficacy | 2 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Sponsor Terminated Study | 4 | 5 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | High Dose | Low Dose | Total |
|---|---|---|---|
| Age Continuous | 13.1 years STANDARD_DEVIATION 2.5 | 13.2 years STANDARD_DEVIATION 2.1 | 13.1 years STANDARD_DEVIATION 2.3 |
| Age, Customized 5-8 years | 1 participants | 0 participants | 1 participants |
| Age, Customized 9-17 years | 18 participants | 20 participants | 38 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 17 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 16 Participants | 17 Participants | 33 Participants |
| Sex: Female, Male Female | 11 Participants | 10 Participants | 21 Participants |
| Sex: Female, Male Male | 8 Participants | 10 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 19 | 11 / 20 |
| serious Total, serious adverse events | 1 / 19 | 1 / 20 |
Outcome results
Primary
Treatment Success PUCAI (Pediatric Ulcerative Colitis Activity Index), mITT/Modified Intent to Treat Population
PUCAI Score (0-85, sum of scores for each): abdominal pain (0/5/10 - no pain/ignored/not ignored), rectal bleeding (0/10/20/30 - none, small amount \<50% of stools, small amount most stools, large amount \>50%), stool consistency (0/5/10 - formed, partially formed, completely formed), # stools/24 hrs. (0/5/10/15 - 0-2/3-5/6-8/\>8), nocturnal bowel/any diarrhea causing wakening (0/10 - no/yes), activity level (0/5/10 - no limitation/occ limitation, severe restrictions). Remission \<10, Mild 10-34, Moderate 35-64, Severe 65-85. Remission defined as Treatment Success.
Time frame: Week 26
Population: MITT subjects who took at least one dose of study medication and did not have baseline stool exam positive for C. difficile, bacterial pathogens or ova/parasites.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High Dose | Treatment Success PUCAI (Pediatric Ulcerative Colitis Activity Index), mITT/Modified Intent to Treat Population | 53.3 percentage of participants |
| Low Dose | Treatment Success PUCAI (Pediatric Ulcerative Colitis Activity Index), mITT/Modified Intent to Treat Population | 60 percentage of participants |
Secondary
Treatment Success PUCAI Amended Endpoint (5 Point Scale Abdominal Pain), mITT
PUCAI Score (0-85, sum of scores for each) abdominal pain (0/2.5/5/7.5/10 - no pain/very mild/mild/moderate/severe), rectal bleeding (0/10/20/30 - none, small amount \<50% of stools, small amount most stools, large amount \>50%), stool consistency (0/5/10 - formed, partially formed, completely formed), # stools/24 hrs. (0/5/10/15 - 0-2/3-5/6-8/\>8), nocturnal bowel/any diarrhea causing wakening (0/10 - no/yes), activity level (0/5/10 - no limitation/occ limitation, severe restrictions). Remission \<10, Mild 10-34, Moderate 35-64, Severe 65-85. Remission is Treatment Success.
Time frame: Week 26
Population: mITT Subjects who took at least one dose of study medication and did not have baseline stool examination positive for C. difficile, bacterial pathogens or ova/parasites.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High Dose | Treatment Success PUCAI Amended Endpoint (5 Point Scale Abdominal Pain), mITT | 60 percentage of participants |
| Low Dose | Treatment Success PUCAI Amended Endpoint (5 Point Scale Abdominal Pain), mITT | 60 percentage of participants |