Ulcerative Colitis
Conditions
Brief summary
Ulcerative colitis is a disease of the large bowel (colon) and rectum in which the lining of the bowel becomes red and swollen. Over time, patients with this disease may experience acute episodes of diarrhea, rectal bleeding and abdominal pain followed by periods of time without disease symptoms. 5-ASA drugs are a standard treatment for ulcerative colitis. Mesalazine is an experimental drug designed to gradually release 5-ASA into the areas of large bowel associated with ulcerative colitis. This study will test the safety and efficacy of mesalazine in keeping ulcerative colitis in remission.
Interventions
DRUGSPD476
2.4 g/day Once Daily (QD)
DRUGAsacol
1.6g/day administered 800 mg Twice Daily (BID)
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* previous diagnosis of ulcerative colitis confirmed by histology that has been considered to be in remission for =\> 30 days * female subjects must be post-menopausal, surgically or biologically sterile, or with a negative urine pregnancy test at screening and on adequate contraception
Exclusion criteria
* proctitis * previous resective colonic surgery * Crohn's disease * hypersensitivity to salicylates * moderate/severe renal impairment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Endoscopic Remission of Ulcerative Colitis (UC) at 6 Months | 6 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 \[ulceration; spontaneous bleeding\]. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Withdrawal Due to Relapse of UC | Over 6 Months | Relapse is defined as withdrawal from the study due to lack of efficacy. |
| Endoscopic Remission of UC With No or Mild Symptoms at 6 Months | 6 Months | Endoscopic remission with no or mild symptoms is defined as an endoscopy score of less than or equal to 1 and a combined symptom score (stool frequency plus rectal bleeding) of less than or equal to 1. Endoscopy score (mucosal appearance) ranges from 0-3 (0 = normal, 1 = mild , 2 = moderate, 3 = severe). Rectal bleeding is assessed on a scale from 0-3 (0 = no rectal bleeding, 1 = streaks of blood, 2 = obvious blood, 3 = mostly blood). Stool frequency is 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). |
| Change From Baseline in Modified Ulcerative Colitis Disease Activity Index (UCDAI) Score at 6 Months | Baseline and 6 months | The modified UCDAI score is the sum of the scores of 4 parameters (stool frequency, rectal bleeding, endoscopy score, and physician global assessment), each scoring between 0 and 3, making 12 the worst score. |
| Short Inflammatory Bowel Disease Questionnaire (SIBDQ) Total Score | 6 Months | Quality of life (QoL) was assessed using the SIBDQ. SIBDQ total score is calculated from the sum of 10 questions. Each question is scored on a scale from 1 (poor QoL) to 7 (good QoL) with total scores ranging from 10 to 70. Higher scores indicate better QoL. |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, Czechia, Denmark, France, Germany, Hungary, India, Mexico, Netherlands, New Zealand, Peru, Poland, Portugal, Romania, Russia, Singapore, South Africa, South Korea, Spain, Sweden, Taiwan, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SPD476 2.4 g/day QD | 415 |
| Asacol 1.6g/day administered 800 mg BID | 411 |
| Total | 826 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 3 |
| Overall Study | Did not return for a visit | 1 | 0 |
| Overall Study | Lack of Efficacy | 50 | 57 |
| Overall Study | Lack of study medication at center | 0 | 1 |
| Overall Study | Lost to Follow-up | 5 | 10 |
| Overall Study | Non-compliance | 0 | 1 |
| Overall Study | Patient request | 10 | 7 |
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Protocol Violation | 3 | 3 |
| Overall Study | Used prohibited corticosteroids | 1 | 0 |
Baseline characteristics
| Characteristic | SPD476 | Asacol | Total |
|---|---|---|---|
| Age, Continuous | 45.0 years STANDARD_DEVIATION 14.05 | 45.2 years STANDARD_DEVIATION 13.44 | 45.1 years STANDARD_DEVIATION 13.74 |
| Age, Customized 18 to 64 years | 380 Participants | 377 Participants | 757 Participants |
| Age, Customized <18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized >=65 years | 35 Participants | 34 Participants | 69 Participants |
| Region of Enrollment Argentina | 4 Participants | 2 Participants | 6 Participants |
| Region of Enrollment Australia | 4 Participants | 3 Participants | 7 Participants |
| Region of Enrollment Belgium | 11 Participants | 11 Participants | 22 Participants |
| Region of Enrollment Brazil | 25 Participants | 28 Participants | 53 Participants |
| Region of Enrollment Canada | 15 Participants | 14 Participants | 29 Participants |
| Region of Enrollment Chile | 4 Participants | 4 Participants | 8 Participants |
| Region of Enrollment Czech Republic | 50 Participants | 54 Participants | 104 Participants |
| Region of Enrollment Denmark | 6 Participants | 5 Participants | 11 Participants |
| Region of Enrollment France | 2 Participants | 3 Participants | 5 Participants |
| Region of Enrollment Germany | 2 Participants | 1 Participants | 3 Participants |
| Region of Enrollment Hungary | 25 Participants | 25 Participants | 50 Participants |
| Region of Enrollment India | 81 Participants | 83 Participants | 164 Participants |
| Region of Enrollment Korea, Republic of | 17 Participants | 14 Participants | 31 Participants |
| Region of Enrollment Mexico | 7 Participants | 10 Participants | 17 Participants |
| Region of Enrollment Netherlands | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment New Zealand | 4 Participants | 2 Participants | 6 Participants |
| Region of Enrollment Peru | 7 Participants | 7 Participants | 14 Participants |
| Region of Enrollment Poland | 29 Participants | 31 Participants | 60 Participants |
| Region of Enrollment Romania | 11 Participants | 10 Participants | 21 Participants |
| Region of Enrollment Russian Federation | 51 Participants | 49 Participants | 100 Participants |
| Region of Enrollment Singapore | 3 Participants | 4 Participants | 7 Participants |
| Region of Enrollment South Africa | 18 Participants | 17 Participants | 35 Participants |
| Region of Enrollment Spain | 3 Participants | 4 Participants | 7 Participants |
| Region of Enrollment Sweden | 3 Participants | 1 Participants | 4 Participants |
| Region of Enrollment Taiwan | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment United Kingdom | 7 Participants | 7 Participants | 14 Participants |
| Region of Enrollment United States | 24 Participants | 22 Participants | 46 Participants |
| Sex: Female, Male Female | 203 Participants | 197 Participants | 400 Participants |
| Sex: Female, Male Male | 212 Participants | 214 Participants | 426 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 415 | 0 / 411 |
| serious Total, serious adverse events | 6 / 415 | 3 / 411 |
Outcome results
Primary
Endoscopic Remission of Ulcerative Colitis (UC) at 6 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: 6 Months
Population: Per Protocol Population (PP) defined as all subjects who either completed the study or withdrew for reasons related to efficacy or AEs and who were deemed to be protocol-compliant.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SPD476 | Endoscopic Remission of Ulcerative Colitis (UC) at 6 Months | 83.7 percent of participants |
| Asacol | Endoscopic Remission of Ulcerative Colitis (UC) at 6 Months | 81.5 percent of participants |
Comparison: The null hypothesis to be tested is that the true difference in proportions is less than or equal to -10%.95% CI: [-0.04, 0.08]
Secondary
Change From Baseline in Modified Ulcerative Colitis Disease Activity Index (UCDAI) Score at 6 Months
The modified UCDAI score is the sum of the scores of 4 parameters (stool frequency, rectal bleeding, endoscopy score, and physician global assessment), each scoring between 0 and 3, making 12 the worst score.
Time frame: Baseline and 6 months
Population: PP
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SPD476 | Change From Baseline in Modified Ulcerative Colitis Disease Activity Index (UCDAI) Score at 6 Months | 0.061 Units on a scale | Standard Deviation 1.1516 |
| Asacol | Change From Baseline in Modified Ulcerative Colitis Disease Activity Index (UCDAI) Score at 6 Months | 0.059 Units on a scale | Standard Deviation 1.2394 |
Secondary
Endoscopic Remission of UC With No or Mild Symptoms at 6 Months
Endoscopic remission with no or mild symptoms is defined as an endoscopy score of less than or equal to 1 and a combined symptom score (stool frequency plus rectal bleeding) of less than or equal to 1. Endoscopy score (mucosal appearance) ranges from 0-3 (0 = normal, 1 = mild , 2 = moderate, 3 = severe). Rectal bleeding is assessed on a scale from 0-3 (0 = no rectal bleeding, 1 = streaks of blood, 2 = obvious blood, 3 = mostly blood). Stool frequency is 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: 6 Months
Population: PP
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SPD476 | Endoscopic Remission of UC With No or Mild Symptoms at 6 Months | 79.0 percent of participants |
| Asacol | Endoscopic Remission of UC With No or Mild Symptoms at 6 Months | 75.6 percent of participants |
Secondary
Short Inflammatory Bowel Disease Questionnaire (SIBDQ) Total Score
Quality of life (QoL) was assessed using the SIBDQ. SIBDQ total score is calculated from the sum of 10 questions. Each question is scored on a scale from 1 (poor QoL) to 7 (good QoL) with total scores ranging from 10 to 70. Higher scores indicate better QoL.
Time frame: 6 Months
Population: Intent to treat (ITT) population defined as all randomized subjects who received at least 1 dose of investigational product. Analysis includes patients who completed an SIBDQ questionnaire at 6 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SPD476 | Short Inflammatory Bowel Disease Questionnaire (SIBDQ) Total Score | 59.523 Units on a scale | Standard Deviation 8.7582 |
| Asacol | Short Inflammatory Bowel Disease Questionnaire (SIBDQ) Total Score | 59.664 Units on a scale | Standard Deviation 7.744 |
Secondary
Withdrawal Due to Relapse of UC
Relapse is defined as withdrawal from the study due to lack of efficacy.
Time frame: Over 6 Months
Population: PP
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SPD476 | Withdrawal Due to Relapse of UC | 12.8 percent of participants |
| Asacol | Withdrawal Due to Relapse of UC | 14.6 percent of participants |