A Double-blind, Randomised, Placebo and Mesalazine Controlled Phase II Study to Explore the Safety and Activity of Dersalazine in Patients With Mild to Moderate Active Colitis

The purpose of the study is to obtain a first clinical assessment of the safety of dersalazine sodium in ulcerative colitis patients with mild to moderate disease.

开始日期2008-12-01

申办/合作机构

Palau Pharma SA

100 项与 Dersalazine 相关的临床结果

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100 项与 Dersalazine 相关的专利（医药）

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项与 Dersalazine 相关的文献（医药）

2014-11-01·Inflammatory Bowel Diseases2区 · 医学

Safety and Activity of Dersalazine Sodium in Patients with Mild-to-moderate Active Colitis

2区 · 医学

Article

作者: Ferran Torres ; Julián Panés ; Roser Vives ; Caridad Pontes

BACKGROUNDDersalazine sodium is an inhibitor of platelet activator factor with potential efficacy in patients with ulcerative colitis through an alternative mechanism of action. The study was a first proof of clinical safety and activity of dersalazine sodium in patients with ulcerative colitis.METHODSA double-blind study of randomized patients with ulcerative colitis (Mayo score ≥ 5 and ≤ 10, including a sigmoidoscopy subscore ≥ 2) to dersalazine sodium 1200 mg/12 h, mesalazine 1200 mg/12 h, or placebo for 4 weeks. Mayo scores were calculated on week 2 (partial Mayo) and week 4 (full Mayo). All patients received open-label mesalazine for 4 additional weeks, and a final visit was done at week 8.RESULTSThe study included 34 patients (13 dersalazine sodium, 10 mesalazine, and 11 placebo). Clinical remission was observed in 46.2% patients treated with dersalazine sodium versus 12.5% in mesalazine and 10% in placebo after 4 weeks of treatment. Colon biopsies showed significantly decreased expression of inflammatory genes in dersalazine sodium patients. Adverse events at least possibly related to treatment were observed in 23%, 12.5%, and 7.6% of patients receiving dersalazine sodium, mesalazine, and placebo, respectively; no serious adverse reactions were reported. Increased liver enzymes were reported in 2/13 patients receiving dersalazine sodium, with normal bilirubin levels; both returned to normal values on treatment interruption.CONCLUSIONSStudies in wider populations are needed to confirm the clinical activity of dersalazine sodium. Weekly measurements of liver function tests may be necessary for early detection of adverse events.

2013-02-01·Inflammatory Bowel Diseases2区 · 医学

Evaluation of Responsive Gene Expression as a Sensitive and Specific Biomarker in Patients with Ulcerative Colitis

2区 · 医学

Article

作者: Julián Panés ; Azucena Salas ; Núria Planell ; Miriam Esteller ; Juan Román ; Caridad Pontes ; Juan J. Lozano ; Dolors Balsa ; Manuel Merlos ; Montserrat Aceituno

BACKGROUNDClinical trials in ulcerative colitis (UC) rely on certain parameters to evaluate responses that are highly subjective or of low sensitivity. Here, using a select group of genes, we tested the accuracy of gene expression analysis as a biomarker of clinical, endoscopic, and histologic improvements.METHODSIntestinal biopsies were obtained from UC patients included in two cohorts. Cohort 1 was used to select for genes whose expression was modulated in active (vs. inactive) UC. Cohort 2 included patients recruited in a phase II study receiving placebo, mesalazine, or dersalazine sodium for 4 weeks. The expression of 44 genes identified in Cohort 1 was assessed at weeks 0 and 4, and was then correlated with biomarkers, as well as with clinical, endoscopic, and histologic scores.RESULTSSignificant changes in the expression of 31 of the 44 genes tested were detected in Cohort 2 at week 4. Gene expression (ΔCt) significantly correlated with the total Mayo score, C-reactive protein (CRP), and fecal calprotectin. The number of genes significantly regulated at week 4 was highly associated with histologic and endoscopic responses. Logistic regression analysis identified four separate genes (IFITM1, ITGB2, IL1R2, IL2RA) whose relative change was independently associated with endoscopic remission with high specificity and sensitivity.CONCLUSIONSChange in the expression of a select set of genes can serve as an early biomarker, one with high specificity and sensitivity to clinical, endoscopic, and histologic responses. This could represent a new tool for identifying early response to treatment in mild to moderately active UC patients.

2012-02-01·British Journal of Pharmacology2区 · 医学

The intestinal anti‐inflammatory effect of dersalazine sodium is related to a down‐regulation in IL‐17 production in experimental models of rodent colitis

2区 · 医学

Article

作者: D Balsa ; ME Rodríguez-Cabezas ; N Garrido-Mesa ; J Xaus ; G Janer ; E Bailón ; J Román ; J Gálvez ; M Cueto-Sola ; D Camuesco ; M Comalada ; M Merlos ; A Zarzuelo ; B Arribas

BACKGROUND AND PURPOSE Dersalazine sodium (DS) is a new chemical entity formed by combining, through an azo bond, a potent platelet activating factor (PAF) antagonist (UR‐12715) with 5‐aminosalicylic acid (5‐ASA). DS has been demonstrated to have anti‐inflammatory effects on trinitrobenzene sulphonic acid (TNBS)‐induced colitis in rats and recently in UC patients in phase II PoC. There is Increasing evidence that Th17 cells have an important role in the pathogenesis of inflammatory bowel disease (IBD). The aim of this study was to further characterize the anti‐inflammatory effects of DS.EXPERIMENTAL APPROACH Effect of DS (10 or 30 mg·kg−1 b.i.d.) on TNBS‐induced colitis in rats was studied after 2 and 7 days with special focus on inflammatory mediators. Additionally, its anti‐inflammatory properties were analysed in two different models of dextran sodium sulphate (DSS)‐induced colitis, BALB/c and C57BL/6 mice, the latter being dependent on IL‐17.KEY RESULTS DS, when administered for 7 days, showed intestinal anti‐inflammatory effects in TNBS‐induced colitis; these effects were observed both macroscopically and through the profile of inflammatory mediators (TNF, IL‐1β, IL‐6 and IL‐17). Although the 2 day treatment with DS did not induce intestinal anti‐inflammatory effects, it was sufficient to reduce the enhanced IL‐17 expression. DS showed beneficial effects on DSS‐induced colitis in C57BL/6 mice and reduced colonic pro‐inflammatory cytokines IL‐1β, IL‐6 and IL‐17. In contrast, it did not exert intestinal anti‐inflammatory effects on DSS‐induced colitis in BALB/c mice.CONCLUSIONS AND IMPLICATIONS DS exerts intestinal anti‐inflammatory activity in different rodent models of colitis through down‐regulation of IL‐17 expression.

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB06251

研发状态

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