New Tablet Formulation and Dosing Regimen of Balsalazide Disodium in Mildly to Moderately Active Ulcerative Colitis

Exclusion Criteria

• •1. Subject has a significant medical, including psychiatric, condition which in the opinion of the investigator precludes participation in the study.
• •2. Subject has a history of allergy or intolerance to aspirin, mesalamine, or other salicylates.
• •3. Subject has recently (within the past 30 days) failed therapy with balsalazide disodium
• •4. Subject has received immunosuppressive therapy (e.g. azothioprine, 6 mercaptopurine) within 30 days, or corticosteroids (oral, intravenous \[IV\] or topical rectal) within 30 days prior to screening.
• •5. Subject has received intra-rectal aminosalicylates within 14 days of screening.
• •6. Subject has had any prior bowel surgery, excepting appendectomy.
• •7. Subject has participated in an investigational drug or device study within the 30 days prior to study screening, with the exception of Salix protocols 3003 \& 3004 entitled: "A multicenter, randomized, double-blind, placebo controlled trial to evaluate the use of mesalamine pellet formulation 1.5G QD to maintain remission from mildly to moderate ulcerative colitis."
• •8. Subject is pregnant or at risk of pregnancy, or is lactating (female subjects only).
• •9. Subject shows evidence of current excessive alcohol consumption or drug dependence.
• •10. Subject has a history of human immunodeficiency virus (HIV) or hepatitis (B and C).
• •11. Subject has other infectious, ischemic, or immunologic diseases with GI involvement.
• •12. Subject has twice the upper limit of normal (ULN) for any of the following LFTs: alanine aminotransferase (ALT/SGPT), aspartate aminotransferase (AST/SGOT), alkaline phosphatase, or total bilirubin (except isolated elevation of unconjugated bilirubin).
• •13. Subject has uncontrolled, clinically significant renal disease manifested by 1.5 × ULN of serum creatinine or blood urea nitrogen (BUN) levels.
• •14. Subject has calculated creatinine clearance level of less than or equal to 60 mL/min.
• •15. Subject has unstable cardiovascular, coagulopathy or pulmonary disease.
• •16. Subject has active malignancy within the last 5 years, except basal cell carcinoma of the skin, or if female, in situ cervical carcinoma that has been surgically excised.
• •17. Subject has any condition or circumstance that would, in the opinion of the investigator, prevent completion of the study or interfere with analysis of study results, including history of noncompliance with treatments or visits.
• •18. Subject has sclerosing cholangitis.
• •19. Subject has positive stool culture for ovum and parasites (O and P) or C. difficile.
• •20. Subject has been treated with infliximab, cyclosporine, natalizumab, or methotrexate for ulcerative colitis within the last 30 days prior to screening.
• •21. Regular use of NSAIDS except cardioprotective ASA (i.e., less than or equal to 162 mg ASA per day).
• •22. Subject has received cell-depleting therapies such as the Adacolumn.
• •23. Subject requires antidiarrheal therapy during screening.
• •24. Subject has clinical or radiographic findings suggestive of serious UC complications such as toxic megacolon or colonic perforation.
• •Females of Reproductive Potential:
• •If a female subject becomes pregnant while on this study, the study drug will be discontinued immediately and the subject followed until the outcome of the pregnancy is known. If a pregnancy occurs, it will be reported in the same manner as an unexpected AE using the guidelines provided in Section 6.4.1.9.
• •Premature Subject Discontinuation:
• •A subject may be discontinued from the study for the following medical or administrative reasons:
• •Occurrence of an AE, which in the judgment of the investigator suggests an unacceptable risk to the subject (The investigator will follow the subject until satisfactory resolution of the AE or the AE is determined to be stable);
• •Development on-study of any condition which, in the opinion of the investigator or the study sponsor, places the subject at an unacceptable medical risk if he/she continues;
• •Pregnancy;
• •Subject request;
• •Institution of additional medical (rescue) therapy for UC. The investigator may discontinue individual subjects from the study at any time. Subjects will be encouraged to complete the study; however they may voluntarily withdraw at any time. The investigator must provide written documentation of the reason for discontinuation on the CRF. Regardless of the reason for withdrawal, all subjects will be asked to undergo an end of therapy evaluation. Every attempt will be made to obtain all the end of study assessments, including all of the subscales of the MMDAI (i.e., bowel frequency, bleeding, physician's assessment, and endoscopy/sigmoidoscopy score).
• •Subjects who withdraw or are withdrawn will not be replaced under this protocol.