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）由一组影响小肠粘膜（克罗恩病）或结肠（溃疡性结肠炎或UC）的炎症疾病表示。 两种疾病都会影响小儿人群；但是，对有关儿科IBD的已发表信息的审查表明，在该领域的意见领导者中，关于Crohn's and U.C.的平均发病，发病率和患病率的意见领导者肯定缺乏共识。在儿童中。 还建议，由于医师可能不愿意将儿童提交放射学，内窥镜检查和活检程序，除非他们严重患病，因此15岁以下的人群的真实发病率可能会被显着低估。由于IBD表现和病原体在儿童和成人患者的临床研究中都相似，因此在儿童中都没有使用。小儿种群中的克罗恩病已经从成年患者的研究中推断出来。被认为在IBD中发挥作用的主要因素是传染性药物和宿主易感性的改变（即细胞介导的免疫或T细胞抑制活性和单核细胞巨噬细胞功能障碍）。前列腺素（PGS）和白细胞（LTS）已与包括IBD在内的许多炎症条件有关。 IBD患者的直肠粘膜产生异常高的血栓烷A2（TXA2），而前列腺素I2（PGI2）水平不受影响或增加。血栓盒在IBD中可能起着重要的致病作用。 在低剂量时，雷德核素特异性抑制了酶血栓烷合成酶。 在人类中，雷德格雷（Ridogrel）在口服以微不足道的第一频繁代谢后完全吸收。 Ridogrel似乎没有通过细胞色素P450酶代谢。 初步数据表明可能涉及过氧化物酶体途径。 迄今为止，尚无有关比较成人和儿童的过氧化物酶体代谢的潜在差异的信息。该试验的主要目的是表征小儿患者在8至18岁的小儿患者中单次口服剂量为2.5或5.0 mg Ridogrel的药代动力学。 次要目标是评估口服2.5 mg或5.0 mg的儿科患者的口服Ridogrel 2.5 mg或5.0 mg的安全性和耐受性（不利经历）。这是一项具有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测试药物的患者将按年龄分为两组：> 8至<13和> 13至<18。 两组将在给药后24小时内监测并接受实验室评估。药代动力学（PK）评估是在研究药物给药之前和后24小时安排的。 尿PK参数将在同一时期进行评估。在这个中心，我们总共招募了五（5）名患者。 其中，三（3）个已经完成了这项研究。 两（2）名患者是筛查失败，因此未给他们服用。 不良事件包括：头痛（1）[被确定与研究药物有关]，以及与药物无关的IV插入部位（1）的疼痛。目前，这项研究保持开放，我们计划在来年再入学10名患者。 GCRC将用于PK采样并监测食物消耗。