Trial Outcomes & Findings for Efficacy and Safety of SPD476 in Maintaining Remission in Patients With Ulcerative Colitis (NCT NCT00151892)
NCT ID: NCT00151892
Last Updated: 2021-06-14
Results Overview
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 \[ulceration; spontaneous bleeding\].
COMPLETED
PHASE3
829 participants
6 Months
2021-06-14
Participant Flow
Participant milestones
| Measure |
SPD476
2.4 g/day once daily (QD)
|
Asacol
1.6g/day administered 800 mg twice daily (BID)
|
|---|---|---|
|
Overall Study
STARTED
|
416
|
413
|
|
Overall Study
COMPLETED
|
340
|
330
|
|
Overall Study
NOT COMPLETED
|
76
|
83
|
Reasons for withdrawal
| Measure |
SPD476
2.4 g/day once daily (QD)
|
Asacol
1.6g/day administered 800 mg twice daily (BID)
|
|---|---|---|
|
Overall Study
Lack of Efficacy
|
50
|
57
|
|
Overall Study
Patient request
|
10
|
7
|
|
Overall Study
Lost to Follow-up
|
5
|
10
|
|
Overall Study
Adverse Event
|
6
|
3
|
|
Overall Study
Protocol Violation
|
3
|
3
|
|
Overall Study
Non-compliance
|
0
|
1
|
|
Overall Study
Pregnancy
|
0
|
1
|
|
Overall Study
Did not return for a visit
|
1
|
0
|
|
Overall Study
Used prohibited corticosteroids
|
1
|
0
|
|
Overall Study
Lack of study medication at center
|
0
|
1
|
Baseline Characteristics
Efficacy and Safety of SPD476 in Maintaining Remission in Patients With Ulcerative Colitis
Baseline characteristics by cohort
| Measure |
SPD476
n=415 Participants
2.4 g/day QD
|
Asacol
n=411 Participants
1.6g/day administered 800 mg BID
|
Total
n=826 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
45.0 years
STANDARD_DEVIATION 14.05 • n=93 Participants
|
45.2 years
STANDARD_DEVIATION 13.44 • n=4 Participants
|
45.1 years
STANDARD_DEVIATION 13.74 • n=27 Participants
|
|
Age, Customized
<18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Customized
18 to 64 years
|
380 Participants
n=93 Participants
|
377 Participants
n=4 Participants
|
757 Participants
n=27 Participants
|
|
Age, Customized
>=65 years
|
35 Participants
n=93 Participants
|
34 Participants
n=4 Participants
|
69 Participants
n=27 Participants
|
|
Sex: Female, Male
Female
|
203 Participants
n=93 Participants
|
197 Participants
n=4 Participants
|
400 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
212 Participants
n=93 Participants
|
214 Participants
n=4 Participants
|
426 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
24 Participants
n=93 Participants
|
22 Participants
n=4 Participants
|
46 Participants
n=27 Participants
|
|
Region of Enrollment
Taiwan
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Region of Enrollment
Spain
|
3 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
7 Participants
n=27 Participants
|
|
Region of Enrollment
Chile
|
4 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
8 Participants
n=27 Participants
|
|
Region of Enrollment
Russian Federation
|
51 Participants
n=93 Participants
|
49 Participants
n=4 Participants
|
100 Participants
n=27 Participants
|
|
Region of Enrollment
India
|
81 Participants
n=93 Participants
|
83 Participants
n=4 Participants
|
164 Participants
n=27 Participants
|
|
Region of Enrollment
France
|
2 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
|
Region of Enrollment
Denmark
|
6 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
11 Participants
n=27 Participants
|
|
Region of Enrollment
Australia
|
4 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
7 Participants
n=27 Participants
|
|
Region of Enrollment
Peru
|
7 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
14 Participants
n=27 Participants
|
|
Region of Enrollment
South Africa
|
18 Participants
n=93 Participants
|
17 Participants
n=4 Participants
|
35 Participants
n=27 Participants
|
|
Region of Enrollment
Netherlands
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Region of Enrollment
Korea, Republic of
|
17 Participants
n=93 Participants
|
14 Participants
n=4 Participants
|
31 Participants
n=27 Participants
|
|
Region of Enrollment
United Kingdom
|
7 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
14 Participants
n=27 Participants
|
|
Region of Enrollment
Hungary
|
25 Participants
n=93 Participants
|
25 Participants
n=4 Participants
|
50 Participants
n=27 Participants
|
|
Region of Enrollment
Czech Republic
|
50 Participants
n=93 Participants
|
54 Participants
n=4 Participants
|
104 Participants
n=27 Participants
|
|
Region of Enrollment
Mexico
|
7 Participants
n=93 Participants
|
10 Participants
n=4 Participants
|
17 Participants
n=27 Participants
|
|
Region of Enrollment
Canada
|
15 Participants
n=93 Participants
|
14 Participants
n=4 Participants
|
29 Participants
n=27 Participants
|
|
Region of Enrollment
Argentina
|
4 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
|
Region of Enrollment
Brazil
|
25 Participants
n=93 Participants
|
28 Participants
n=4 Participants
|
53 Participants
n=27 Participants
|
|
Region of Enrollment
Belgium
|
11 Participants
n=93 Participants
|
11 Participants
n=4 Participants
|
22 Participants
n=27 Participants
|
|
Region of Enrollment
Poland
|
29 Participants
n=93 Participants
|
31 Participants
n=4 Participants
|
60 Participants
n=27 Participants
|
|
Region of Enrollment
Singapore
|
3 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
7 Participants
n=27 Participants
|
|
Region of Enrollment
Romania
|
11 Participants
n=93 Participants
|
10 Participants
n=4 Participants
|
21 Participants
n=27 Participants
|
|
Region of Enrollment
Germany
|
2 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
|
Region of Enrollment
New Zealand
|
4 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
|
Region of Enrollment
Sweden
|
3 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: 6 MonthsPopulation: 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.
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 \[ulceration; spontaneous bleeding\].
Outcome measures
| Measure |
SPD476
n=343 Participants
2.4 g/day QD
|
Asacol
n=336 Participants
1.6g/day administered 800 mg BID
|
|---|---|---|
|
Endoscopic Remission of Ulcerative Colitis (UC) at 6 Months
|
83.7 percent of participants
|
81.5 percent of participants
|
SECONDARY outcome
Timeframe: Over 6 MonthsPopulation: PP
Relapse is defined as withdrawal from the study due to lack of efficacy.
Outcome measures
| Measure |
SPD476
n=343 Participants
2.4 g/day QD
|
Asacol
n=336 Participants
1.6g/day administered 800 mg BID
|
|---|---|---|
|
Withdrawal Due to Relapse of UC
|
12.8 percent of participants
|
14.6 percent of participants
|
SECONDARY outcome
Timeframe: 6 MonthsPopulation: PP
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).
Outcome measures
| Measure |
SPD476
n=343 Participants
2.4 g/day QD
|
Asacol
n=336 Participants
1.6g/day administered 800 mg BID
|
|---|---|---|
|
Endoscopic Remission of UC With No or Mild Symptoms at 6 Months
|
79.0 percent of participants
|
75.6 percent of participants
|
SECONDARY outcome
Timeframe: Baseline and 6 monthsPopulation: PP
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.
Outcome measures
| Measure |
SPD476
n=290 Participants
2.4 g/day QD
|
Asacol
n=281 Participants
1.6g/day administered 800 mg BID
|
|---|---|---|
|
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
|
0.059 Units on a scale
Standard Deviation 1.2394
|
SECONDARY outcome
Timeframe: 6 MonthsPopulation: 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.
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.
Outcome measures
| Measure |
SPD476
n=155 Participants
2.4 g/day QD
|
Asacol
n=155 Participants
1.6g/day administered 800 mg BID
|
|---|---|---|
|
Short Inflammatory Bowel Disease Questionnaire (SIBDQ) Total Score
|
59.523 Units on a scale
Standard Deviation 8.7582
|
59.664 Units on a scale
Standard Deviation 7.7440
|
Adverse Events
SPD476
Asacol
Serious adverse events
| Measure |
SPD476
n=415 participants at risk
2.4 g/day QD
|
Asacol
n=411 participants at risk
1.6g/day administered 800 mg BID
|
|---|---|---|
|
Gastrointestinal disorders
Colitis
|
0.24%
1/415
Safety population defined as all randomized subjects who received at least 1 dose of investigational medication.
|
0.00%
0/411
Safety population defined as all randomized subjects who received at least 1 dose of investigational medication.
|
|
Gastrointestinal disorders
Colitis ulcerative
|
0.24%
1/415
Safety population defined as all randomized subjects who received at least 1 dose of investigational medication.
|
0.24%
1/411
Safety population defined as all randomized subjects who received at least 1 dose of investigational medication.
|
|
Infections and infestations
Appendicitis
|
0.24%
1/415
Safety population defined as all randomized subjects who received at least 1 dose of investigational medication.
|
0.00%
0/411
Safety population defined as all randomized subjects who received at least 1 dose of investigational medication.
|
|
Infections and infestations
Bronchitis
|
0.24%
1/415
Safety population defined as all randomized subjects who received at least 1 dose of investigational medication.
|
0.00%
0/411
Safety population defined as all randomized subjects who received at least 1 dose of investigational medication.
|
|
Injury, poisoning and procedural complications
Fallopian tube perforation
|
0.00%
0/415
Safety population defined as all randomized subjects who received at least 1 dose of investigational medication.
|
0.24%
1/411
Safety population defined as all randomized subjects who received at least 1 dose of investigational medication.
|
|
Injury, poisoning and procedural complications
Post procedural hemorrhage
|
0.24%
1/415
Safety population defined as all randomized subjects who received at least 1 dose of investigational medication.
|
0.00%
0/411
Safety population defined as all randomized subjects who received at least 1 dose of investigational medication.
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/415
Safety population defined as all randomized subjects who received at least 1 dose of investigational medication.
|
0.24%
1/411
Safety population defined as all randomized subjects who received at least 1 dose of investigational medication.
|
|
Nervous system disorders
Radiculitis brachial
|
0.24%
1/415
Safety population defined as all randomized subjects who received at least 1 dose of investigational medication.
|
0.00%
0/411
Safety population defined as all randomized subjects who received at least 1 dose of investigational medication.
|
|
Pregnancy, puerperium and perinatal conditions
Ectopic pregnancy
|
0.00%
0/415
Safety population defined as all randomized subjects who received at least 1 dose of investigational medication.
|
0.24%
1/411
Safety population defined as all randomized subjects who received at least 1 dose of investigational medication.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.24%
1/415
Safety population defined as all randomized subjects who received at least 1 dose of investigational medication.
|
0.00%
0/411
Safety population defined as all randomized subjects who received at least 1 dose of investigational medication.
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
- Publication restrictions are in place
Restriction type: OTHER