RIDOGREL IN CLINICALLY STABLE, NON ACTIVE ULCERATIVE COLITIS PEDS PAT

利多格雷治疗临床稳定、非活动性溃疡性结肠炎 PAT

• 批准号: 6264414
• 负责人: JEFFREY L. BLUMER
• 金额: $ 1.92万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6264414
• 关键词: child (0-11); clinical research; drug adverse effect; drug screening /evaluation; enzyme inhibitors; gastrointestinal agents; gastrointestinal disorder chemotherapy; human subject; human therapy evaluation; pediatric pharmacology; pediatrics; pharmacokinetics; ulcerative colitis

Inflammatory Bowel Disease (IBD) is represented by a group of inflammatory conditions affecting the mucosa of the small intestine (Crohn's Disease) or colon (Ulcerative Colitis or UC). Both diseases affect the pediatric population; however, review of the published information on IBD in pediatrics reveals a definite lack of consensus amongst the opinion leaders in this field regarding the mean age of onset, incidence, and prevalence rates of Crohn's and U.C. in children. It is also suggested that since physicians may be reluctant to submit children to radiological, endoscopic, and biopsy procedures unless they are acutely ill, the true incidence may be significantly underestimated for the population under the age of 15. Because the IBD presentation and pathogenesis is similar in both pediatric and adult patients, and clinical studies in children are lacking, the guidelines for use of the available therapies for both U.C. and Crohn's disease in the pediatric population have been extrapolated from studies in adult patients. The major factors thought to play a rold in IBD are infectious agents and altered host susceptibility (i.e., impaired cell mediated immunity or T-cell suppressor activity and monocyte-macrophage dysfunction). Prostaglandins (PGs) and leukotrienes (LTs) have been implicated in many inflammatory conditions, including IBD. The rectal mucosa of patients with IBD produce abnormally high levels of thromboxane A2 (TXA2), while prostaglandin I2 (PGI2) levels are unaffected or increased. Thromboxanes may play a major pathogenic role in IBD. At low doses, ridogrel specifically inhibits the enzyme thromboxane synthetase. In man, ridogrel is completely absorbed after oral administration with negligible first-pass metabolism. Ridogrel does not appear to be metabolized through cytochrome P450 enzymes. Preliminary data suggest that peroxisomal pathways may be involved. To date, no information is available on potential differences in peroxisomal metabolism comparing adults and children. The primary objective of this trial is to characterize the pharmacokinetics of a single oral dose of 2.5 or 5.0 mg ridogrel in pediatric patients age 8 to <18 with UC. The secondary objective is to evaluate the safety and tolerability (adverse experiences) of oral ridogrel 2.5 mg or 5.0 mg given to pediatric patients with ulcerative colitis. This is a multicenter, single-blind, randomized, pharmacokinetic trial with a parallel group design. Patients who qualify to enter the study and receive randomized test drug will be stratified into two groups by age: >8 to <13 and >13 to <18. Both groups will be monitored and undergo laboratory evaluations for the subsequent 24 hours after dosing. Pharmacokinetic (PK) evaluations are scheduled just prior to study drug administration and for 24 hours afterward. Urinary PK parameters will be evaluated over the same period. At this center, we have enrolled a total of five (5) patients. Of these, three (3) have completed the study. Two (2) patients were screen failures, thus they were not dosed. Adverse events included: headache (1) [which was determined to be related to study drug], and pain at the IV insertion site (1) that was not related to drug. At this time, the study remains open and we plan to enroll an additional 10 patients in the coming year. The GCRC will be used for the PK sampling and to monitor food consumption.

炎症性肠病（IBD）由一组影响小肠（克罗恩病）或结肠（溃疡性结肠炎或UC）粘膜的炎性病症表示。 这两种疾病均影响儿科人群;然而，对已发表的儿科IBD信息的审查显示，该领域的意见领袖对克罗恩病和UC的平均发病年龄、发病率和患病率缺乏共识。小儿 这也表明，由于医生可能不愿意提交儿童的放射，内窥镜和活检程序，除非他们是急性病，真正的发病率可能会显着低估了15岁以下的人口。由于IBD的表现和发病机制在儿童和成人患者中相似，并且缺乏儿童临床研究，因此，针对UC和UC的可用疗法的使用指南。和克罗恩病在儿科人群中的发病率是从成人患者的研究中推断出来的。被认为在IBD中起作用的主要因素是感染因子和改变的宿主易感性（即，受损的细胞介导的免疫或T细胞抑制活性和单核细胞-巨噬细胞功能障碍）。前列腺素（PG）和白三烯（LT）与许多炎症性疾病有关，包括IBD。 IBD患者的直肠粘膜产生异常高水平的血栓素A2（TXA 2），而前列腺素I2（PGI 2）水平不受影响或增加。血栓烷类可能在IBD中起主要致病作用。 在低剂量下，雷多格雷特异性抑制血栓烷合成酶。 在人类中，口服给药后，瑞多格雷完全吸收，首过代谢可忽略不计。 瑞多格雷似乎不通过细胞色素P450酶代谢。 初步数据表明，过氧化物酶体途径可能参与。 到目前为止，还没有关于成人和儿童过氧化物酶体代谢潜在差异的信息。本试验的主要目的是描述8至<18岁儿童UC患者单次口服2.5或5.0 mg利多格雷的药代动力学特征。 次要目的是评价口服2.5 mg或5.0 mg利多格雷治疗溃疡性结肠炎儿童患者的安全性和耐受性（不良反应）。这是一项平行组设计的多中心、单盲、随机、药代动力学试验。 有资格进入研究并接受随机试验药物的患者将按年龄分为两组：&gt;8至<13 and >13至&lt;18。 给药后24小时内，将对两组进行监测和实验室评价。药代动力学（PK）评价安排在研究药物给药前即刻和给药后24小时进行。 将在同一时期评价尿液PK参数。在该中心，我们共入组了5例患者。 其中，3人已完成研究。 2例患者筛选失败，因此未给药。 不良事件包括：头痛（1例）[确定与研究药物相关]和IV插入部位疼痛（1例），与药物无关。目前，该研究仍处于开放状态，我们计划在明年再招募10名患者。 GCRC将用于PK采样和监测摄食量。