Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Comparison of Once a Day Dose Compared to 2 Doses/Day

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00505778
Recruitment Status : Completed
First Posted : July 23, 2007
Results First Posted : May 12, 2011
Last Update Posted : April 22, 2013
Sponsor:
Information provided by (Responsible Party):
Warner Chilcott

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Investigator);   Primary Purpose: Treatment
Condition Ulcerative Colitis
Interventions Drug: Mesalamine Once-Daily
Drug: Mesalamine Twice-Daily
Enrollment 1027
Recruitment Details Enrollment began 9 Aug 2007
Pre-assignment Details  
Arm/Group Title Mesalamine Once-Daily Mesalamine Twice-Daily
Hide Arm/Group Description an oral, once daily (QD) mesalamine regimen (1.6 - 2.4 g/day) an oral, twice daily (BID) mesalamine regimen (1.6 - 2.4 g/day)
Period Title: Overall Study
Started 514 513
Intent to Treat (ITT) Population 512 511
Completed 380 378
Not Completed 134 135
Reason Not Completed
Adverse Event             2             7
Physician Decision             8             14
Lost to Follow-up             17             23
Unable to Meet Protocol Criteria             4             1
Protocol Violation             7             9
Withdrawal by Subject             29             14
Relapse             65             65
Took No Study Drug             2             2
Arm/Group Title Mesalamine Once-Daily Mesalamine Twice-Daily Total
Hide Arm/Group Description an oral, once daily (QD) mesalamine regimen (1.6 - 2.4 g/day) an oral, twice daily (BID) mesalamine regimen (1.6 - 2.4 g/day) Total of all reporting groups
Overall Number of Baseline Participants 514 513 1027
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 514 participants 513 participants 1027 participants
< 65 years old 409 414 823
> = 65 years old 103 97 200
[1]
Measure Description: ITT Population
Gender   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 514 participants 513 participants 1027 participants
Female 261 268 529
Male 251 243 494
[1]
Measure Description: ITT Population
Region of Enrollment   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 514 participants 513 participants 1027 participants
Canada 6 8 14
United States 506 503 1009
[1]
Measure Description: ITT Population
1.Primary Outcome
Title Percentage of Patients Remaining in Remission at Month 6, ITT Population, Determined by the Simple Clinical Colitis Activity Index (SCCAI)
Hide Description Remission defined as SCCAI <5. Simple Clinical Colitis Activity Index: minimum score 0, maximum score 19, reflects disease activity over the 24 hours prior to completion. Composite Score: bowel frequency (day, 0-3) (night, 0-2), defecation urgency (0-3), blood in stool (0-3), general well being (0-4), extracolonic features (arthritis, pyoderma gangrenosum, erythema nodosum, uveitis - 1 per manifestation).
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Mesalamine Once-Daily Mesalamine Twice-Daily
Hide Arm/Group Description:
an oral, once daily (QD) mesalamine regimen (1.6 - 2.4 g/day)
an oral, twice daily (BID) mesalamine regimen (1.6 - 2.4 g/day)
Overall Number of Participants Analyzed 512 511
Measure Type: Number
Unit of Measure: Percentage of Participants
90.5 91.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mesalamine Once-Daily, Mesalamine Twice-Daily
Comments Assumed true remission rate is 70% with no difference in remission rates between QD and BID dosing.The non-inferiority margin used in hypothesis testing was set to 10%.
Type of Statistical Test Non-Inferiority or Equivalence
Comments To establish non-inferiority for primary efficacy variable at 2-sided upper confidence bound of 95% with 90% power, 442 patients per treatment group were required to be analyzable for primary efficacy analysis. Assuming 10% enrolled would not be analyzable, 1000 patients would be enrolled. If the 95% confidence interval's upper bound interval for the difference between the Asacol BID and Asacol QD group is <10%, then non-inferiority of Asacol QD is claimed.
Statistical Test of Hypothesis P-Value 0.5016
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified by prior Asacol dose Category
Method of Estimation Estimation Parameter BID-QD Difference in Remission Rates
Estimated Value 1.3
Confidence Interval (2-Sided) 95%
-2.3 to 4.9
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Patients Remaining in Remission at Month 3, ITT Population
Hide Description Remission defined as SCCAI < 5. Simple Clinical Colitis Activity Index: minimum score 0, maximum score 19, reflects disease activity over the 24 hours prior to completion. Composite Score: bowel frequency (day, 0-3) (night, 0-2), defecation urgency (0-3), blood in stool (0-3), general well being (0-4), extracolonic features (arthritis, pyoderma gangrenosum, erythema nodosum, uveitis - 1 per manifestation).
Time Frame 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Mesalamine Once-Daily Mesalamine Twice-Daily
Hide Arm/Group Description:
an oral, once daily (QD) mesalamine regimen (1.6 - 2.4 g/day)
an oral, twice daily (BID) mesalamine regimen (1.6 - 2.4 g/day)
Overall Number of Participants Analyzed 512 511
Measure Type: Number
Unit of Measure: Percentage of Participants
94.8 95.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mesalamine Once-Daily, Mesalamine Twice-Daily
Comments Assumed true remission rate is 70% with no difference in remission rates between QD and BID dosing.The non-inferiority margin used in hypothesis testing was set to 10%.
Type of Statistical Test Non-Inferiority or Equivalence
Comments To establish non-inferiority for primary efficacy variable at 2-sided upper confidence bound of 95% with 90% power, 442 patients per treatment group were required to be analyzable for primary efficacy analysis. Assuming 10% enrolled would not be analyzable, 1000 patients would be enrolled. If the 95% confidence interval's upper bound interval for the difference between the Asacol BID and Asacol QD group is <10%, then non-inferiority of Asacol QD is claimed.
Statistical Test of Hypothesis P-Value 0.5426
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified by prior Asacol dose Category
Method of Estimation Estimation Parameter BID-QD Difference in Remission Rates
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
-1.8 to 3.5
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Patients Remaining in Remission at Month 12, ITT Population
Hide Description Remission defined as SCCAI score < 5. Simple Clinical Colitis Activity Index: minimum score 0, maximum score 19, reflects disease activity over the 24 hours prior to completion. Composite Score: bowel frequency (day, 0-3) (night, 0-2), defecation urgency (0-3), blood in stool (0-3), general well being (0-4), extracolonic features (arthritis, pyoderma gangrenosum, erythema nodosum, uveitis - 1 per manifestation).
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Mesalamine Once-Daily Mesalamine Twice-Daily
Hide Arm/Group Description:
an oral, once daily (QD) mesalamine regimen (1.6 - 2.4 g/day)
an oral, twice daily (BID) mesalamine regimen (1.6 - 2.4 g/day)
Overall Number of Participants Analyzed 512 511
Measure Type: Number
Unit of Measure: Percentage of Participants
85.4 85.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mesalamine Once-Daily, Mesalamine Twice-Daily
Comments Assumed true remission rate is 70% with no difference in remission rates between QD and BID dosing.The non-inferiority margin used in hypothesis testing was set to 10%.
Type of Statistical Test Non-Inferiority or Equivalence
Comments To establish non-inferiority for primary efficacy variable at 2-sided upper confidence bound of 95% with 90% power, 442 patients per treatment group were required to be analyzable for primary efficacy analysis. Assuming 10% enrolled would not be analyzable, 1000 patients would be enrolled. If the 95% confidence interval's upper bound interval for the difference between the Asacol BID and Asacol QD group is <10%, then non-inferiority of Asacol QD is claimed.
Statistical Test of Hypothesis P-Value 0.9770
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified by prior Asacol dose Category
Method of Estimation Estimation Parameter BID-QD Difference in Remission Rates
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-4.6 to 4.7
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Number of Subjects Who Relapse/Flare Within 6 Months, ITT Population
Hide Description Relapse/flare is defined as SCCAI >= 5. Simple Clinical Colitis Activity Index: minimum score 0, maximum score 19, reflects disease activity over the 24 hours prior to completion. Composite Score: bowel frequency (day, 0-3) (night, 0-2), defecation urgency (0-3), blood in stool (0-3), general well being (0-4), extracolonic features (arthritis, pyoderma gangrenosum, erythema nodosum, uveitis - 1 per manifestation).
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Mesalamine Once-Daily Mesalamine Twice-Daily
Hide Arm/Group Description:
an oral, once daily (QD) mesalamine regimen (1.6 - 2.4 g/day)
an oral, twice daily (BID) mesalamine regimen (1.6 - 2.4 g/day)
Overall Number of Participants Analyzed 512 511
Measure Type: Number
Unit of Measure: Participants
45 39
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mesalamine Once-Daily, Mesalamine Twice-Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4726
Comments [Not Specified]
Method Log Rank
Comments Stratified by prior Asacol dose Category
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.170
Confidence Interval (2-Sided) 95%
0.762 to 1.796
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Total MARS (Medication Adherence Report Scale) Questionnaire Scores, ITT Population, Month 6
Hide Description MARS: Composite score for the following statements: I change how many times per day I take my medicine, I forget to use it, I stop taking it for a while, I only use it when I am having active symptoms, I decide to miss out on a dose, I take less than instructed, I take more than instructed, I avoid using it if I can, I use it regularly every day (reverse scored): 5-never, 4-rarely, 3-sometimes, 2-often, 1-very often. Minimum score 9, maximum score 45.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Mesalamine Once-Daily Mesalamine Twice-Daily
Hide Arm/Group Description:
an oral, once daily (QD) mesalamine regimen (1.6 - 2.4 g/day)
an oral, twice daily (BID) mesalamine regimen (1.6 - 2.4 g/day)
Overall Number of Participants Analyzed 512 511
Mean (Standard Error)
Unit of Measure: MARS Score
42.3  (0.23) 41.8  (0.24)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mesalamine Once-Daily, Mesalamine Twice-Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1753
Comments [Not Specified]
Method ANOVA
Comments ANOVA with prior Asacol dose category as factor.
Method of Estimation Estimation Parameter Difference BID-QD in Least Square Mean
Estimated Value -0.45
Confidence Interval (2-Sided) 95%
-1.09 to 0.20
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants Indicating Ulcerative Colitis in Remission (Patient Defined Remission Index), ITT Population, Month 6
Hide Description Is your ulcerative colitis in remission (not active)? Y/N
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Mesalamine Once-Daily Mesalamine Twice-Daily
Hide Arm/Group Description:
an oral, once daily (QD) mesalamine regimen (1.6 - 2.4 g/day)
an oral, twice daily (BID) mesalamine regimen (1.6 - 2.4 g/day)
Overall Number of Participants Analyzed 512 511
Measure Type: Number
Unit of Measure: Percentage of Participants
83.1 86.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mesalamine Once-Daily, Mesalamine Twice-Daily
Comments Assumed true remission rate is 70% with no difference in remission rates between QD and BID dosing.The non-inferiority margin used in hypothesis testing was set to 10%.
Type of Statistical Test Non-Inferiority or Equivalence
Comments To establish non-inferiority for primary efficacy variable at 2-sided upper confidence bound of 95% with 90% power, 442 patients per treatment group were required to be analyzable for primary efficacy analysis. Assuming 10% enrolled would not be analyzable, 1000 patients would be enrolled. If the 95% confidence interval's upper bound interval for the difference between the Asacol BID and Asacol QD group is <10%, then non-inferiority of Asacol QD is claimed.
Statistical Test of Hypothesis P-Value 0.1557
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified by prior Asacol dose Category
Method of Estimation Estimation Parameter Difference BID-QD Remission Rates
Estimated Value 3.6
Confidence Interval (2-Sided) 95%
-1.3 to 8.5
Estimation Comments [Not Specified]
Time Frame 12 months
Adverse Event Reporting Description ITT Population, Only Immediately Reportable Events (SAEs or withdrawal due to AEs) collected for this study. Data collected between 9 Aug 2007 and 29 Jul 2009.
 
Arm/Group Title Mesalamine Once-Daily Mesalamine Twice-Daily
Hide Arm/Group Description an oral, once daily (QD) mesalamine regimen (1.6 - 2.4 g/day) an oral, twice daily (BID) mesalamine regimen (1.6 - 2.4 g/day)
All-Cause Mortality
Mesalamine Once-Daily Mesalamine Twice-Daily
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Mesalamine Once-Daily Mesalamine Twice-Daily
Affected / at Risk (%) Affected / at Risk (%)
Total   18/512 (3.52%)   9/511 (1.76%) 
Cardiac disorders     
Cardiomyopathy  1  0/512 (0.00%)  1/511 (0.20%) 
Coronary Artery Disease  1  0/512 (0.00%)  1/511 (0.20%) 
Atrial Fibrillation  1  1/512 (0.20%)  0/511 (0.00%) 
Cardiac Failure Congestive  1  1/512 (0.20%)  0/511 (0.00%) 
Myocardial Infarcation  1  1/512 (0.20%)  0/511 (0.00%) 
Gastrointestinal disorders     
Abdominal Pain  1  0/512 (0.00%)  1/511 (0.20%) 
Ascites  1  0/512 (0.00%)  1/511 (0.20%) 
Constipation  1  0/512 (0.00%)  1/511 (0.20%) 
Rectal Haemorrhage  1  0/512 (0.00%)  1/511 (0.20%) 
Anal fistula  1  1/512 (0.20%)  0/511 (0.00%) 
General disorders     
Chest Pain  1  1/512 (0.20%)  0/511 (0.00%) 
Hepatobiliary disorders     
Cholangitis  1  1/512 (0.20%)  0/511 (0.00%) 
Cholelithiasis  1  2/512 (0.39%)  0/511 (0.00%) 
Jaundice Cholestatic  1  1/512 (0.20%)  0/511 (0.00%) 
Infections and infestations     
Appendicitis  1  2/512 (0.39%)  0/511 (0.00%) 
Diverticulitis  1  1/512 (0.20%)  0/511 (0.00%) 
Injury, poisoning and procedural complications     
Clavicle Fracture  1  1/512 (0.20%)  0/511 (0.00%) 
Rib Fracture  1  1/512 (0.20%)  0/511 (0.00%) 
Spinal Compression Fracture  1  1/512 (0.20%)  0/511 (0.00%) 
Metabolism and nutrition disorders     
Dehydration  1  0/512 (0.00%)  1/511 (0.20%) 
Hyponatraemia  1  1/512 (0.20%)  0/511 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Breast Cancer  1  0/512 (0.00%)  1/511 (0.20%) 
Oesophageal Carcinoma  1  0/512 (0.00%)  1/511 (0.20%) 
Small Cell Lung Cancer Metastatic  1  0/512 (0.00%)  1/511 (0.20%) 
Renal Cancer  1  1/512 (0.20%)  0/511 (0.00%) 
Thyroid Neoplasm  1  1/512 (0.20%)  0/511 (0.00%) 
Uterine Leiomyoma  1  1/512 (0.20%)  0/511 (0.00%) 
Nervous system disorders     
Altered State of Consciousness  1  1/512 (0.20%)  0/511 (0.00%) 
Convulsion  1  1/512 (0.20%)  0/511 (0.00%) 
Transient Ischaemic Attack  1  1/512 (0.20%)  0/511 (0.00%) 
Renal and urinary disorders     
Renal Failure Acute  1  0/512 (0.00%)  2/511 (0.39%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary Embolism  1  0/512 (0.00%)  1/511 (0.20%) 
Haemothorax  1  1/512 (0.20%)  0/511 (0.00%) 
Vascular disorders     
Deep Vein Thrombosis  1  0/512 (0.00%)  1/511 (0.20%) 
Hypertension  1  1/512 (0.20%)  0/511 (0.00%) 
Thrombophlebitis  1  1/512 (0.20%)  0/511 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Mesalamine Once-Daily Mesalamine Twice-Daily
Affected / at Risk (%) Affected / at Risk (%)
Total   0/512 (0.00%)   0/511 (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.
Results Point of Contact
Name/Title: Grexan Wulff, Manager Regulatory Affairs
Organization: Warner Chilcott
Phone: 973-442-3376
Responsible Party: Warner Chilcott
ClinicalTrials.gov Identifier: NCT00505778     History of Changes
Other Study ID Numbers: 2007021
First Submitted: July 20, 2007
First Posted: July 23, 2007
Results First Submitted: April 18, 2011
Results First Posted: May 12, 2011
Last Update Posted: April 22, 2013