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Efficacy and Safety of SPD476 in Maintaining Remission in Patients With Ulcerative Colitis

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ClinicalTrials.gov Identifier: NCT00151892
Recruitment Status : Completed
First Posted : September 9, 2005
Results First Posted : September 21, 2010
Last Update Posted : March 20, 2017
Sponsor:
Information provided by (Responsible Party):
Shire

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Ulcerative Colitis
Interventions Drug: SPD476
Drug: Asacol
Enrollment 829
Recruitment Details  
Pre-assignment Details  
Arm/Group Title SPD476 Asacol
Hide Arm/Group Description 2.4 g/day once daily (QD) 1.6g/day administered 800 mg twice daily (BID)
Period Title: Overall Study
Started 416 413
Completed 340 330
Not Completed 76 83
Reason Not Completed
Lack of Efficacy             50             57
Patient request             10             7
Lost to Follow-up             5             10
Adverse Event             6             3
Protocol Violation             3             3
Non-compliance             0             1
Pregnancy             0             1
Did not return for a visit             1             0
Used prohibited corticosteroids             1             0
Lack of study medication at center             0             1
Arm/Group Title SPD476 Asacol Total
Hide Arm/Group Description 2.4 g/day QD 1.6g/day administered 800 mg BID Total of all reporting groups
Overall Number of Baseline Participants 415 411 826
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 415 participants 411 participants 826 participants
<18 years 0 0 0
18 to 64 years 380 377 757
>=65 years 35 34 69
[1]
Measure Description: Baseline characteristics were calculated from the Safety Population (n = 826) defined as all randomized subjects who received at least 1 dose of investigational product.
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 415 participants 411 participants 826 participants
45.0  (14.05) 45.2  (13.44) 45.1  (13.74)
[1]
Measure Description: Baseline characteristics were calculated from the Safety Population (n = 826) defined as all randomized subjects who received at least 1 dose of investigational product.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 415 participants 411 participants 826 participants
Female
203
  48.9%
197
  47.9%
400
  48.4%
Male
212
  51.1%
214
  52.1%
426
  51.6%
[1]
Measure Description: Baseline characteristics were calculated from the Safety Population (n = 826) defined as all randomized subjects who received at least 1 dose of investigational product.
Region of Enrollment   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 415 participants 411 participants 826 participants
United States 24 22 46
Taiwan 1 0 1
Spain 3 4 7
Chile 4 4 8
Russian Federation 51 49 100
India 81 83 164
France 2 3 5
Denmark 6 5 11
Australia 4 3 7
Peru 7 7 14
South Africa 18 17 35
Netherlands 1 0 1
Korea, Republic of 17 14 31
United Kingdom 7 7 14
Hungary 25 25 50
Czech Republic 50 54 104
Mexico 7 10 17
Canada 15 14 29
Argentina 4 2 6
Brazil 25 28 53
Belgium 11 11 22
Poland 29 31 60
Singapore 3 4 7
Romania 11 10 21
Germany 2 1 3
New Zealand 4 2 6
Sweden 3 1 4
[1]
Measure Description: Baseline characteristics were calculated from the Safety Population (n = 826) defined as all randomized subjects who received at least 1 dose of investigational product.
1.Primary Outcome
Title Endoscopic Remission of Ulcerative Colitis (UC) at 6 Months
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title SPD476 Asacol
Hide Arm/Group Description:
2.4 g/day QD
1.6g/day administered 800 mg BID
Overall Number of Participants Analyzed 343 336
Measure Type: Number
Unit of Measure: percent of participants
83.7 81.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SPD476, Asacol
Comments The null hypothesis to be tested is that the true difference in proportions is less than or equal to -10%.
Type of Statistical Test Non-Inferiority or Equivalence
Comments A 2-sided 95% confidence interval (CI) for the difference in the percentages of subjects in remission at 6 months of the two treatment groups will be computed. Non-inferiority of SPD476 to Asacol will be concluded if the lower limit of the 95% CI lies above the non-inferiority margin of -10%.
Method of Estimation Estimation Parameter Difference in proportions
Estimated Value 0.02
Confidence Interval 95%
-0.04 to 0.08
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Withdrawal Due to Relapse of UC
Hide Description Relapse is defined as withdrawal from the study due to lack of efficacy.
Time Frame Over 6 Months
Hide Outcome Measure Data
Hide Analysis Population Description
PP
Arm/Group Title SPD476 Asacol
Hide Arm/Group Description:
2.4 g/day QD
1.6g/day administered 800 mg BID
Overall Number of Participants Analyzed 343 336
Measure Type: Number
Unit of Measure: percent of participants
12.8 14.6
3.Secondary Outcome
Title Endoscopic Remission of UC With No or Mild Symptoms at 6 Months
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
PP
Arm/Group Title SPD476 Asacol
Hide Arm/Group Description:
2.4 g/day QD
1.6g/day administered 800 mg BID
Overall Number of Participants Analyzed 343 336
Measure Type: Number
Unit of Measure: percent of participants
79.0 75.6
4.Secondary Outcome
Title Change From Baseline in Modified Ulcerative Colitis Disease Activity Index (UCDAI) Score at 6 Months
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
PP
Arm/Group Title SPD476 Asacol
Hide Arm/Group Description:
2.4 g/day QD
1.6g/day administered 800 mg BID
Overall Number of Participants Analyzed 290 281
Mean (Standard Deviation)
Unit of Measure: Units on a scale
0.061  (1.1516) 0.059  (1.2394)
5.Secondary Outcome
Title Short Inflammatory Bowel Disease Questionnaire (SIBDQ) Total Score
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title SPD476 Asacol
Hide Arm/Group Description:
2.4 g/day QD
1.6g/day administered 800 mg BID
Overall Number of Participants Analyzed 155 155
Mean (Standard Deviation)
Unit of Measure: Units on a scale
59.523  (8.7582) 59.664  (7.7440)
Time Frame [Not Specified]
Adverse Event Reporting Description Safety population defined as all randomized subjects who received at least 1 dose of investigational medication.
 
Arm/Group Title SPD476 Asacol
Hide Arm/Group Description 2.4 g/day QD 1.6g/day administered 800 mg BID
All-Cause Mortality
SPD476 Asacol
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
SPD476 Asacol
Affected / at Risk (%) Affected / at Risk (%)
Total   6/415 (1.45%)   3/411 (0.73%) 
Gastrointestinal disorders     
Colitis  1/415 (0.24%)  0/411 (0.00%) 
Colitis ulcerative  1/415 (0.24%)  1/411 (0.24%) 
Infections and infestations     
Appendicitis  1/415 (0.24%)  0/411 (0.00%) 
Bronchitis  1/415 (0.24%)  0/411 (0.00%) 
Injury, poisoning and procedural complications     
Fallopian tube perforation  0/415 (0.00%)  1/411 (0.24%) 
Post procedural hemorrhage  1/415 (0.24%)  0/411 (0.00%) 
Musculoskeletal and connective tissue disorders     
Intervertebral disc protrusion  0/415 (0.00%)  1/411 (0.24%) 
Nervous system disorders     
Radiculitis brachial  1/415 (0.24%)  0/411 (0.00%) 
Pregnancy, puerperium and perinatal conditions     
Ectopic pregnancy  0/415 (0.00%)  1/411 (0.24%) 
Respiratory, thoracic and mediastinal disorders     
Asthma  1/415 (0.24%)  0/411 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
SPD476 Asacol
Affected / at Risk (%) Affected / at Risk (%)
Total   0/415 (0.00%)   0/411 (0.00%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Timothy Whitaker, M.D.
Organization: Shire Pharmaceutical
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT00151892     History of Changes
Other Study ID Numbers: SPD476-304
2004-004184-29 ( EudraCT Number )
First Submitted: September 7, 2005
First Posted: September 9, 2005
Results First Submitted: August 26, 2010
Results First Posted: September 21, 2010
Last Update Posted: March 20, 2017