Active Ulcerative Colitis, Remission of Ulcerative Colitis
Conditions
Keywords
Ulcerative Colitis, 5-Aminosalicylate
Brief summary
The purpose of this study is to demonstrate that the new modified oral extended-release Pentasa® 500mg tablet is at least as efficacious as the currently marketed Pentasa® 500mg tablet in active mild to moderate Ulcerative Colitis (UC) and also in maintenance of quiescent disease.
Detailed description
A multi-centre, randomized, double-blind, non-inferiority trial comparing the efficacy and safety of a new modified oral extended release Pentasa® (mesalamine) 500 mg tablet to the currently marketed Pentasa® (mesalamine) 500 mg tablet in subjects with active mild to moderate ulcerative colitis treated with 4 g/day for 8 weeks and in maintenance of remission of ulcerative colitis in subjects treated with 2 g/day for 24 weeks. The study involves male or non-pregnant female subjects aged 18 to 75 years. Subjects were randomised on entry into the trial, and if they were in remission at the end of the 8-week Active Phase or the 4-week Run-in Phase, they were eligible for enrolment into the 24-week Maintenance Phase, remaining on the original randomised treatment.
Interventions
500 mg tablet (modified extended release)
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
for Active phase: * Newly diagnosed or recurrent, mild to moderate Ulcerative Colitis patients. * Extent of colonic involvement confirmed within the past 36 months * UCDAI score of at least 3 but not greater than 8 and a score of at least 1 for endoscopy * Screening tests to rule out any abnormalities in stool, heart or kidney. * Male or non-pregnant females between 18 to 75 years. * Women of childbearing potential to use efficacious contraception as judged by the investigator. * Written informed consent given. Inclusion Criteria for Maintenance phase: * Newly recruited subjects with documented mild to moderate UC entering the Run-in Phase: in clinical remission for at least 1 month and for a maximum of 3 years, and receiving 5-ASA 1.4 to 2.5 g/day for maintenance of quiescent disease * Subjects from Active Phase: meeting remission criteria after the 8-week active period * Extent of colonic involvement confirmed within the past 36 months by colonoscopy * In complete remission at entry into the Maintenance Phase, defined as i) a score of 0 or 1 for stool frequency; ii) a score of 0 for rectal bleeding; iii) a score of 0 for endoscopy findings; and iv) a Physician's Global Assessment (PGA) score of 0 or 1 * Screening tests to rule out any abnormalities in stool, heart or kidney.
Exclusion criteria
* Use of 5-ASA products at a dose \>2.5g/day within 7 days prior to entry. * Proctitis, short bowel syndrome, prior bowel surgery, severe UC, other forms of Inflammatory Bowel Disease * Infectious diseases, parasites, bacterial pathogens * Allergy to aspirin or salicylate * Liver or kidney abnormalities * Alcohol or drug abuse * Pregnancy * Cancer * Bleeding disorders, ulcers, autoimmune diseases * Mental disorders * Participation in clinical trial in last 30 days * Inability to fill in diary cards / comply with protocol requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Active Phase: Proportion of Active Subjects Achieving Overall Improvement | From baseline to week 8 | Overall improvement is defined as either a complete remission or a clinical response to therapy as measured by the Ulcerative Colitis Disease Activity Index (UCDAI). Complete remission is defined as: i) a score of 0 or 1 for stool frequency; ii) a score of 0 for rectal bleeding; iii) a score of 0 for endoscopy findings and iv) a Physician's Global Assessment (PGA) score of 0 or 1. A clinical response to therapy in the active disease phase is defined as i) improvement in the baseline PGA score; ii) improvement in endoscopy findings and in at least one other clinical assessment (stool frequency, rectal bleeding); iii) no worsening in any other clinical assessment; iv) a decrease of 2 or more points on the UCDAI score. |
| Maintenance Phase: Proportion of Subjects Experiencing Relapse | Up to week 24 | Relapse is defined as a UCDAI score of at least 3 and a score of at least 1 for endoscopy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Adverse Events | From baseline to week 24 | Safety dataset represents all patients in all study phases exposed to study drug at anytime during study. Safety dataset was a combination of the active, run-in and maintenance phases and therefore it is not possible to report the adverse events per phase. |
Countries
Canada
Participant flow
Recruitment details
Total number of unique patients enrolled in the study is 288 whereby 190 patients were enrolled in the Active Phase and 98 patients were enrolled in the Run-In Phase. The patients enrolled in the Maintenance Phase are a combination of patients who completed the Active (82) and Run In (71) Phases and were eligible to move forward into Maintenance.
Participants by arm
| Arm | Count |
|---|---|
| Pentasa® Modified Extended Release 5-ASA (5-Aminosalicylate)
5-ASA (5-Aminosalicylate): 500 mg tablet (modified extended release) | 139 |
| Pentasa® 5-ASA (5-Aminosalicylate)
5-ASA (5-Aminosalicylate): 500 mg tablet | 146 |
| Total | 285 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Active Phase ITT | Adverse Event | 8 | 7 |
| Active Phase ITT | Did not meet inclusion/exclusion | 1 | 3 |
| Active Phase ITT | Lack of Efficacy | 1 | 2 |
| Active Phase ITT | Lost to Follow-up | 0 | 1 |
| Active Phase ITT | Subject moved, site closed | 1 | 1 |
| Active Phase ITT | Withdrawal by Subject | 0 | 3 |
| Maintenance Phase ITT | Adverse Event | 3 | 6 |
| Maintenance Phase ITT | Lack of Efficacy | 2 | 2 |
| Maintenance Phase ITT | Lost to Follow-up | 0 | 1 |
| Maintenance Phase ITT | Physician Decision | 0 | 1 |
| Maintenance Phase ITT | Protocol Violation | 1 | 1 |
| Maintenance Phase ITT | Site withdrew, subject away, lost IMP | 3 | 5 |
| Maintenance Phase ITT | Withdrawal by Subject | 1 | 0 |
| Run-In Phase - 4 Weeks | Adverse Event | 2 | 1 |
| Run-In Phase - 4 Weeks | Did not meet incl/excl criteria | 5 | 10 |
| Run-In Phase - 4 Weeks | Lack of Efficacy | 2 | 1 |
| Run-In Phase - 4 Weeks | Lost to Follow-up | 1 | 0 |
| Run-In Phase - 4 Weeks | Withdrawal by Subject | 4 | 1 |
Baseline characteristics
| Characteristic | Pentasa® Modified Extended Release | Pentasa® | Total |
|---|---|---|---|
| Age, Continuous Active Phase | 44.2 years STANDARD_DEVIATION 12.88 | 44.5 years STANDARD_DEVIATION 12.53 | 44.35 years STANDARD_DEVIATION 12.71 |
| Age, Continuous Maintenance Phase | 46.4 years STANDARD_DEVIATION 12.2 | 45.8 years STANDARD_DEVIATION 13.45 | 46.1 years STANDARD_DEVIATION 12.83 |
| Age, Customized Active Phase | 45 years | 43.5 years | 44.3 years |
| Age, Customized Maintenance Phase | 48 years | 44.5 years | 46.3 years |
| Region of Enrollment Canada | 139 participants | 146 participants | 285 participants |
| Sex/Gender, Customized Active Phase, Female | 30 participants | 34 participants | 64 participants |
| Sex/Gender, Customized Active Phase, Male | 48 participants | 44 participants | 92 participants |
| Sex/Gender, Customized Maintenance Phase, Female | 28 participants | 29 participants | 57 participants |
| Sex/Gender, Customized Maintenance Phase, Male | 33 participants | 39 participants | 72 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 27 / 143 | 28 / 144 |
| serious Total, serious adverse events | 7 / 143 | 2 / 144 |
Outcome results
Primary
Active Phase: Proportion of Active Subjects Achieving Overall Improvement
Overall improvement is defined as either a complete remission or a clinical response to therapy as measured by the Ulcerative Colitis Disease Activity Index (UCDAI). Complete remission is defined as: i) a score of 0 or 1 for stool frequency; ii) a score of 0 for rectal bleeding; iii) a score of 0 for endoscopy findings and iv) a Physician's Global Assessment (PGA) score of 0 or 1. A clinical response to therapy in the active disease phase is defined as i) improvement in the baseline PGA score; ii) improvement in endoscopy findings and in at least one other clinical assessment (stool frequency, rectal bleeding); iii) no worsening in any other clinical assessment; iv) a decrease of 2 or more points on the UCDAI score.
Time frame: From baseline to week 8
Population: Per Protocol Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pentasa® Modified Extended Release | Active Phase: Proportion of Active Subjects Achieving Overall Improvement | 64.1 percentage of participants |
| Pentasa® | Active Phase: Proportion of Active Subjects Achieving Overall Improvement | 69.2 percentage of participants |
Primary
Maintenance Phase: Proportion of Subjects Experiencing Relapse
Relapse is defined as a UCDAI score of at least 3 and a score of at least 1 for endoscopy
Time frame: Up to week 24
Population: Per Protocol Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pentasa® Modified Extended Release | Maintenance Phase: Proportion of Subjects Experiencing Relapse | 24.6 % of subjects with relapse (90% CI) |
| Pentasa® | Maintenance Phase: Proportion of Subjects Experiencing Relapse | 11.8 % of subjects with relapse (90% CI) |
Secondary
Frequency of Adverse Events
Safety dataset represents all patients in all study phases exposed to study drug at anytime during study. Safety dataset was a combination of the active, run-in and maintenance phases and therefore it is not possible to report the adverse events per phase.
Time frame: From baseline to week 24
Population: Safety dataset for Active and Maintenance Phases
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pentasa® Modified Extended Release | Frequency of Adverse Events | 52.4 percentage of patients with TEAEs |
| Pentasa® | Frequency of Adverse Events | 45.1 percentage of patients with TEAEs |