Oral administration of non-absorbable delayed release @entity4446 is locally active in the gut, exerts a systemic immune effect and alleviates XXXX with low rate of side effects: results of double blind Phase II clinical trial.

@entity1 @entity7275 @entity4446 @entity8729 @entity10227 @entity30
UNASSIGNED: Therapy for @entity30 (CD) with @entity10227 is limited by systemic side effects. A novel formulation of fixed-dose, delayed-release @entity4446 (DR-6MP) was developed, with local effect on the gut immune system and minimal absorption. The aim of this study was to evaluate the safety and efficacy of DR- @entity7275 in @entity1 with moderately severe CD compared to systemically delivered @entity4446 ( @entity4446 ). Seventy CD @entity1 were enrolled into a 12-week, double-blind controlled trial. The primary end-point was the percentage of subjects with clinical remission [Crohn's Disease Activity Index (CDAI)  <  150] or clinical response (100-point CDAI reduction). Twenty-six (56  5%) and 13 (54  2%) subjects from the DR- @entity7275 and @entity4446 cohorts, respectively, completed the study. DR- @entity7275 had similar efficacy to @entity4446 following 12 weeks of treatment. However, the time to maximal clinical response was 8 weeks for DR- @entity7275 versus 12 weeks for @entity4446 . A higher proportion of @entity1 on DR- @entity7275 showed clinical remission at week 8. A greater improvement in Inflammatory Bowel Disease Questionnaire (IBDQ) score was noted in the DR- @entity7275 group. DR- @entity7275 led to a decrease of @entity8729 (+) expression on T cells, implying a reduction of lymphocyte adhesion to site of inflammation. DR- @entity7275 was safer than @entity4446 , with significantly fewer adverse events (AEs). There was no evidence of drug-induced leucopenia in the DR- @entity7275 group; the proportion of subjects who developed hepatotoxicity was lower for the DR- @entity7275 . Non-absorbable DR- @entity7275 is safe and biologically active in the gut. It is clinically effective, exerting a systemic immune response with low systemic bioavailability and a low incidence of side effects.
