study of the safety and tolerability of alth12 versus mesalamine enema in subjects with left-sided ulcerative colitis

Conditions: Ulcerative Colitis

Summary: this phase i study will be a closely monitored trial of a small number of subjects to establish, preliminarily, the tolerability and safety of two alth12 enema formulations: alth12-1:4 and alth12-2:4. the study will be conducted in two parts. the first part will be the assessment of the safety and tolerability of a single dose of alth12-1:4 or the comparator, mesalamine (4.0g 5-asa) followed by an assessment of repeated administrations of study drug (alth12-1:4 or comparator) for 6 weeks. the second part will be the same assessment for alth12-2:4. three subjects will be enrolled in each cohort: 2 to receive alth12 enema therapy and 1 subject to receive comparator enema therapy. a total of up to 9 patients will be enrolled in this study, allowing for up to 3 replacement or additional patients.


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 active disease or disease in remission. * eligible subjects will have a documented history of ulcerative colitis, and a modified ucdai with a sigmoidoscopy score of 1 point or less and physician's rating of disease score of 1 point or less (mild or remission). * laboratory data: 1. white blood cell count between 4,500 and 10,000 cells/ml 2. platelet count: 150,000-450,000 cells/ml 3. hemoglobin \> 10.0 g/dl 4. total bilirubin \< 1.5 mg/dl 5. aspartate aminotransferase \< 100 u/dl 6. alanine aminotransferase \< 100 u/dl 7. alkaline phosphatase \< 250 u/dl 8. blood urine nitrogen \< 40 mg/dl 9. creatinine \< 1.5 mg/dl 10. amylase \< 150 u/l * satisfied one of the following: * female subjects of childbearing potential must have a negative serum 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: subjects will be excluded if: * they have documented history of 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 2 or greater (moderate or severe disease) or an endoscopy score of 2 or greater. * they have shown evidence of high grade dysplasia on 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. * they have received systemic steroids or immunosuppressants within the previous 4 weeks. * treatment in the last 2 weeks that included antibiotic, antifungal, antiparasitic medications, or rectally administered steroids (e.g. cortenema®) and/or 5-asa enema (e.g. rowasa®). * 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 abuse. * they have a known allergy to n-acetylcysteine or mesalamine. * 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. * any condition which the study physician judges to preclude safe participation in the study or to confound the evaluation of the study outcome.

Keywords: colitis inflammatory bowel disease ulcerative colitis rectal administration enema mesalamine