Official Title: “A Phase IV, Multi-Center, Open-Label Study to Assess Clinical Recurrence Related to Compliance With Treatment With MMXÔ Mesalamine 2.4g/Day Given Once Daily for the Maintenance of Quiescent Ulcerative Colitis (UC)”

To evaluate the percentage of subjects with clinical recurrence at 6 months.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: March 2010

Intervention(s) in this Clinical Trial

• Drug: MMX Mesalamine
  • MMX™ mesalamine 2.4g/day to 4.8g/day QD (two to four 1.2g tablets MMX™ mesalamine, dosed QD,respectively).

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1

Primary Measures

• To evaluate the percentage of subjects with clinical recurrence
  • Time Frame: 6 months
    Safety Issue?: No

Secondary Measures

• To assess the time to clinical recurrence
  • Time Frame: at various times over 14 months
    Safety Issue?: No
• To evaluate the percentage of subjects with clinical recurrence
  • Time Frame: at various times over 14 months
    Safety Issue?: No
• To assess clinical recurrence related to subject compliance with MMX™ mesalamine
  • Time Frame: at various times over 14 months
    Safety Issue?: No
• To evaluate the percentage of subjects with quiescent UC
  • Time Frame: at various times over 14 months
    Safety Issue?: No
• Endoscopic remission
  • Time Frame: at various times over 14 months
    Safety Issue?: No
• safety and tolerability of MMX™ mesalamine
  • Time Frame: at various times over 14 months
    Safety Issue?: Yes

Inclusion Criteria - Acute Phase:

• 1. Male and female subjects aged at least 18 years with active mild to moderate UC may enter the Acute Phase of the study.
• 2. Must have a previous diagnosis of UC confirmed by histology and endoscopy or radiology.
• 3. Males or non-pregnant, non-lactating FOCP who have a negative serum pregnancy test prior to entering the study and who are using adequate forms of contraception for the duration of the study.
• 4. General medical assessment must be satisfactory and there must not be clinically significant and relevant abnormalities.
• 5. Subject must have had >2 acute episodes of UC (a documented episode of increased bowel frequency with rectal blood loss for which UC therapy was intensified) in their medical history.
• 6. Subjects who have relapsed on maintenance therapy after 2 weeks with doses of mesalamine at: a. <2.0g/day, will be allowed into the Acute Phase at 2.4g/day QD, or b. between 2.0g/day - 3.0g/day will be allowed into the Acute Phase at 4.8g/day QD.

Inclusion Criteria - Maintenance Phase:

• 1. Subjects determined to be quiescent at study entry on prior oral mesalamine therapy will be eligible to enter directly into the Maintenance Phase.
• 2. UC must have been considered to be quiescent, with scores of zero for both rectal bleeding and bowel movements.

Exclusion Criteria - Acute Phase:

• 1. Subjects who have been in relapse for >6 weeks.
• 2. Female subjects who are pregnant or lactating, including females with a positive pregnancy test at screening.
• 3. Subjects must not have used another investigational agent within the last 30 days prior to enrollment.
• 4. Subjects who have unsuccessfully treated their current relapse with steroids or a mesalamine dose of >2.0 g/day.
• 5. Subjects who have relapsed on maintenance therapy with doses of mesalamine >2.0g/day.
• If the subject had a recent dose reduction from 2.0g/day to less than or equal to 2.0g/day and relapsed within 2 weeks of that dose reduction, the subject will not be eligible.
• 6. Subjects who have used systemic or rectal steroids within the last 4 weeks prior to Baseline, immunosuppressants within the last 6 weeks, antibiotic use within the last 7 days or chronic use of any anti-inflammatory drugs within 7 days prior to Baseline.
• 7. Subjects with hypersensitivity to salicylates/aspirin are excluded.
• 8. Subjects with moderate or severe hepatic impairment.
• 9. Subjects with Crohn's Disease, proctitis (where the extent of inflammation is less than or equal to 15cm), short bowel syndrome, bleeding disorders, or active peptic ulcer disease.
• 10. Subjects with asthma are excluded only if they are known to be mesalamine-sensitive.
• 11. Subjects with a positive stool culture for enteric pathogens (including Salmonella, Shigella, Yersinia, Aeromonas, Plesiomonas or Campylobacter) are excluded, as are those with C. difficile toxin present or with ova or parasites as detected by microscopy.
• 12. Subjects who have a history of previous colonic surgery.
• 13. Subjects with moderate or severe renal impairment are contra-indicated for treatment with mesalamine compounds and are excluded from the study.
• 14. Subjects with current or recurrent disease that could affect the colon, the action, absorption or disposition of the study drug, or clinical or laboratory assessments.
• 15. Subjects with current or relevant previous history of serious, severe or unstable (acute or progressive) physical or psychiatric illness, any medical disorder that may require treatment or make the patient unlikely to fully complete the study, or any condition that presents undue risk from the study drug or procedures.
• 16. Subjects with a history of alcohol or other substance abuse within the previous year.
• 17. Subjects who withdrew from a mesalamine trial due to a possibly or probably related severe AE or SAE are not eligible to enter this study.
• Exclusion Criteria - Maintenance Phase (in addition to above inclusion for the Acute

Phase):

• 1. Subjects who have withdrawn from the Acute Phase before study visit A3.
• 2. Subjects with severe UC according to the PGA.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Shire Pharmaceutical Development

Overall Clinical Trial Officials and Contacts

Sunanda V. Kane, M.D. Principal Investigator Mayo Clinic, Rochester, MN  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00446849

Study ID Number: SPD476-404

ClinicalTrials.gov Identifier: NCT00446849

Health Authority: United States: Food and Drug Administration