Ulcerative Colitis
Conditions
Keywords
Mesalamine, Asacol, Ulcerative colitis, induction therapy, acute disease, mild to moderate, Active Ulcerative Colitis (mild to moderate)
Brief summary
The primary objective of the study is to determine the efficacy of Asacol™ 4.8 g/day (800 mg tablets) to induce clinical and endoscopic remission after 6 weeks of treatment compared to placebo in subjects with active ulcerative colitis (UC).
Detailed description
The 800 mg Asacol™ tablets from Tillotts Pharma AG are being marketed in over 30 countries, mainly in Europe and Asia. Approved dosages for the treatment of active UC are between 2.4 and 4.8 g/day in analogy to the approved 400 mg dosage form. The present trial is planned to generate efficacy data to support the safe use of a 4.8 g/day dose of the 800 mg dosage form in a well defined population of patients with mildly to moderately active UC. In keeping with the EMEA UC guideline the study will have a placebo-controlled 6 weeks induction treatment. After 6 weeks, treatment success will be evaluated using the modified UC disease activity index as primary efficacy measurement.
Interventions
DRUGMesalamin
4.8g/day, 800 mg tablets
Sponsors
Tillotts Pharma AG
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
(1) Male or non-pregnant, non-lactating females, 18 years of age or older. (2) Documented diagnosis of UC with disease extending at least 15 cm from the anal verge. (3) Active UC defined by: (a) modified UC-DAI score of 4-10 with (b) sigmoidoscopy component score ≥ 2 and (c) rectal bleeding component score ≥ 1 (4) Ability of subject to participate fully in all aspects of this clinical trial. (5) Written informed consent must be obtained and documented.
Exclusion criteria
1. Severe UC defined by the following criteria: ³6 bloody stools daily with one or more of the following: 1. oral temperature \> 37.8°C or \> 100.0°F 2. pulse \> 90/min 3. hemoglobin \< 10 g/dL 2. Previously failed treatment with a mesalazine dose of \> 2.0 g/day. 3. Current relapse lasting \> 6 weeks in the opinion of the investigator. 4. Treatment with 5-ASA at a dose of \>2.0g/day within 1 week prior to randomisation 5. Treatment with systemic or rectal steroids within 4 weeks prior to randomization. 6. Treatment with immunosuppressants within 6 weeks prior to randomization. 7. Treatment with infliximab or other biologics within 3 months prior to randomization. 8. Treatment with systemic antibiotics for UC within 7 days prior to randomization. 9. Treatment with probiotics within 7 days prior to randomization. 10. Treatment with anti-diarrheals within 7 days prior to randomization. 11. Treatment with nicotine patch within 7 days prior to randomization. 12. Received any investigational drug within 30 days prior to randomization. 13. History of colectomy or partial colectomy. 14. History of definite dysplasia in colonic biopsies. 15. Crohn's disease. 16. Known bleeding disorders. 17. Immediate or significant risk of toxic megacolon. 18. Hypersensitivity to salicylates, aspirin, sulfasalazine or 5-ASA. 19. Serum creatinine \> 1.5 times the upper limit of the normal range. 20. AST, ALT, total bilirubin or alkaline phosphatase \> 2 times the upper limit of the normal range. 21. Serious underlying disease other than UC which in the opinion of the investigator may interfere with the subject's ability to participate fully in the study. 22. History of alcohol or drug abuse which in the opinion of the investigator may interfere with the subject's ability to comply with the study procedures. 23. Stools positive for clostridium difficile. 24. Pregnant or lactating women. 25. Prior enrolment in the current study and had received study treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Achieve Clinical Remission in Subjects With Active Ulcerative Colitis (UC). | 6 weeks | Clinical remission defined as stool frequency score of 0, rectal bleeding score of 0, no urgency |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Endoscopic Remission | 6 weeks | Endoscopic remission is defined as a sigmoidoscopy score of 1 or less |
| Clinical Remission | 10 weeks | Clinical remission defined as a score of 0 for stool frequency, 0 for rectal bleeding and no urgency |
| Improvement | 6 weeks | Improvement is defined as a reduction of at least 3 points from baseline in the modified UC-DAI score. (minumum 3, maximum 7, higher absolute UC-DAI scores indicate more severe disease) |
Countries
Belarus, India, Turkey (Türkiye), Ukraine
Participant flow
Recruitment details
November 2009 - February 2011
Pre-assignment details
Screen failures, not complying to inclusion and exclusion criteria
Participants by arm
| Arm | Count |
|---|---|
| Mesalamin Mesalamin: 4.8g/day, 800 mg tablets The study drug will be given for 10 weeks. All treatment regimens will be orally administered, with or without food. Subjects randomized to the Asacol™ 4.8 g/day treatment group will receive three 800 mg Asacol™ tablets in the morning and three 800 mg Asacol™ tablets in the evening. | 140 |
| Placebo Placebo to Mesalamin: 4.8g/day, 800 mg tablets The study drug will be given for 10 weeks. All treatment regimens will be orally administered, with or without food. Subjects randomized to the placebo treatment group will receive three placebo tablets in the morning and three placebo tablets in the evening. | 141 |
| Total | 281 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 12 | 30 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Other | 3 | 6 |
| Overall Study | Withdrawal by Subject | 6 | 9 |
Baseline characteristics
| Characteristic | Mesalamin | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 42.6 years STANDARD_DEVIATION 14.3 | 40.72 years STANDARD_DEVIATION 13.8 | 41.8 years STANDARD_DEVIATION 14.1 |
| Race/Ethnicity, Customized Asian | 26 participants | 31 participants | 57 participants |
| Race/Ethnicity, Customized White | 114 participants | 110 participants | 224 participants |
| Region of Enrollment Belarus | 47 participants | 44 participants | 91 participants |
| Region of Enrollment India | 26 participants | 31 participants | 57 participants |
| Region of Enrollment Turkey | 13 participants | 11 participants | 24 participants |
| Region of Enrollment Ukraine | 54 participants | 55 participants | 109 participants |
| Sex: Female, Male Female | 53 Participants | 66 Participants | 119 Participants |
| Sex: Female, Male Male | 87 Participants | 75 Participants | 162 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 27 / 140 | 47 / 141 |
| serious Total, serious adverse events | 0 / 140 | 3 / 141 |
Outcome results
Primary
To Achieve Clinical Remission in Subjects With Active Ulcerative Colitis (UC).
Clinical remission defined as stool frequency score of 0, rectal bleeding score of 0, no urgency
Time frame: 6 weeks
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mesalamin | To Achieve Clinical Remission in Subjects With Active Ulcerative Colitis (UC). | 42 participants |
| Placebo | To Achieve Clinical Remission in Subjects With Active Ulcerative Colitis (UC). | 29 participants |
p-value: 0.069Chi-squared
Secondary
Clinical Remission
Clinical remission defined as a score of 0 for stool frequency, 0 for rectal bleeding and no urgency
Time frame: 10 weeks
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mesalamin | Clinical Remission | 57 Participants |
| Placebo | Clinical Remission | 30 Participants |
p-value: <0.001Chi-squared
Secondary
Endoscopic Remission
Endoscopic remission is defined as a sigmoidoscopy score of 1 or less
Time frame: 10 weeks
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mesalamin | Endoscopic Remission | 73 Participants |
| Placebo | Endoscopic Remission | 52 Participants |
p-value: 0.01Chi-squared
Secondary
Endoscopic Remission
Endoscopic remission is defined as a sigmoidoscopy score of 1 or less
Time frame: 6 weeks
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mesalamin | Endoscopic Remission | 64 Participants |
| Placebo | Endoscopic Remission | 35 Participants |
p-value: <0.001Chi-squared
Secondary
Improvement
Improvement is defined as a reduction of at least 3 points from baseline in the modified UC-DAI score. (minumum 3, maximum 7, higher absolute UC-DAI scores indicate more severe disease)
Time frame: 10 weeks
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mesalamin | Improvement | 88 Participants |
| Placebo | Improvement | 57 Participants |
p-value: <0.001Chi-squared
Secondary
Improvement
Improvement is defined as a reduction of at least 3 points from baseline in the modified UC-DAI score. (minumum 3, maximum 7, higher absolute UC-DAI scores indicate more severe disease)
Time frame: 6 weeks
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mesalamin | Improvement | 83 Participants |
| Placebo | Improvement | 47 Participants |
p-value: <0.001Chi-squared
Post Hoc
To Achieve Clinical Remission in the Patient Population Confirmed by the Central Reader
Clinical Remission, defined as stool frequency score of 0, rectal bleeding score of 0 and absence of urgency in subjects with adequate disease extent at baseline confirmed by central reading.
Time frame: 6 weeks
Population: modified ITT, eligibility confirmed by central reader
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mesalamin | To Achieve Clinical Remission in the Patient Population Confirmed by the Central Reader | 31 Participants |
| Placebo | To Achieve Clinical Remission in the Patient Population Confirmed by the Central Reader | 12 Participants |
p-value: 0.011Chi-squared