study of the safety and efficacy of zoenasa® versus mesalamine enema in subjects with left-sided ulcerative colitis

Conditions: Ulcerative Colitis; Left-sided Ulcerative Colitis; Distal Ulcerative Colitis

Summary: this double-blind, randomized, comparator-controlled phase ii study is designed to establish the safety and efficacy of zoenasa rectal gel compared to mesalamine enema in subjects with left-sided ulcerative colitis, as measured by the modified ulcerative colitis disease activity index (ucdai), over 6 weeks of treatment. in this study, two cohorts of subjects will receive either zoenasa-1:4 (1.0g nac; 4.0g 5-asa) investigational drug enema therapy or comparator mesalamine enema (4.0g 5-asa). the study will enroll subjects randomized equally into the 2 cohorts. each cohort will enroll approximately 60 subjects. the two arms of the trial will be enrolled concurrently in a randomized fashion.


Eligibility criteria:
inclusion criteria: * male and female subjects are eligible if they are ≥ 18 years of age and ≤ 64 years. * they have a documented history of idiopathic ulcerative colitis based on endoscopic and/or histologic findings involving the left side of the colon, with mild to moderate active disease. * eligible subjects will have a documented history of ulcerative colitis, and a modified ucdai score of 4-10, inclusive, with a physician's rating of disease score of 2 points or less (mild or moderate active ulcerative colitis), rectal bleeding score of 1 or more (based on subject diary), and mucosal appearance score (based on endoscopy) of 1 point or more at baseline. * laboratory data: * white blood cell count between 4.0 - 12.0 k/mm3 * platelet count: 150 - 500 k/mm3 * hemoglobin \> 10.0 g/dl * total bilirubin \< 1.5 mg/dl * aspartate aminotransferase \< 100 u/dl * alanine aminotransferase \< 100 u/dl * alkaline phosphatase \< 250 u/dl * blood urine nitrogen \< 40 mg/dl * creatinine \< 1.5 mg/dl * satisfies one of the following: * female subjects of childbearing potential must have a negative urine pregnancy test at screening; surgically sterile, post-menopausal, abstinent, or patient or partner agree to use a medically appropriate form of birth control from screening to until 1 month after the last dose of study medication. * male subjects must be surgically sterile, abstinent, or patient or partner compliant with a contraceptive regimen from screening to until 1 month after the last dose of study medication. * they are able to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures. exclusion criteria: * they have documented history of proximal or universal ulcerative colitis, proctitis or active proctitis confined to 15cm or less from the anal verge. * they demonstrate signs and symptoms of fulminant colitis, bowel stricture, toxic megacolon, an anticipated need for blood transfusion for gastrointestinal bleeding, or demonstrate evidence of peritonitis. * they receive a physician's rating of disease severity as part of the modified ucdai of 3 (severe disease) or an aggregate score of 11 or greater. * they have shown prior documented history of evidence of high grade dysplasia on biopsy from endoscopic examinations. * their stool contains enteric pathogens or clostridium difficile toxins. * they have a history of recurrent clostridium difficile infection. * they have prior history of biologic therapy within the previous 4 years. * they have received systemic steroids or immunosuppressants within the previous 4 weeks. * treatment in the last 14 days that included antibiotic, antifungal, antiparasitic medications, or rectally administered steroids (e.g. cortenema®) or mesalamine enema (rowasa®). * treatment in the last 7 days that included mesalamine (5-asa) via oral administration (e.g. asacol®, lialda®, balsalazide, etc). * they have a history of cancer (defined as malignancy within 5 years except for squamous cell or basal cell cancers of the skin), asthma, or bronchospasm. * positive pregnancy test or lactating subjects. * there is evidence of chemical substance abuse. * they have had repeated anti-inflammatory drug treatment (longer than 3 days at doses that exceed those available without a prescription) within the previous 7 days (with exception of aspirin at doses of 325mg/day or less for prophylaxis of cardiac disease), or initiated new non-steroidal anti-inflammatory (nsaid) treatment within the last 30 days. * they have a known allergy to n-acetylcysteine or mesalamine, or have a history of serious aes related to their use (including, but not limited to pancreatitis or hepatitis). * they have a history of failure to retain enemas. * other clinically significant diseases that could interfere with the protocol compliance appear. these would include clinically important hematological, renal, hepatic, metabolic, psychiatric, central nervous system (cns), pulmonary or cardiovascular disease. * use of any investigational medication within the previous 90 days. * any condition which the study physician judges to preclude safe participation in the study or to confound the evaluation of the study outcome.

Keywords: ulcerative colitis uc left-sided ulcerative colitis distal ulcerative colitis zoenasa mesalamine mesalazine 5-asa 5-aminosalicylic acid n-acetylcysteine acetylcysteine nac enema rectal gel