WIRB-A RANDOMIZED, DOUBLE-BLIND, PARALLEL GROUP STUDY TO ASSESS THE SAFETY AND E

WIRB-一项评估安全性和有效性的随机、双盲、平行小组研究

• 批准号: 8167295
• 负责人: ALI A BADER
• 金额: $ 0.2万
• 依托单位: CHILDREN'S RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-20 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167295
• 关键词: 17 year old; 9 year old; Abdominal Pain; Adolescent; Adult; Age; Biological Markers; Biopsy; Blood Pressure; Blood Volume; Blood specimen; Body Temperature; Body Weight; Body Weight decreased; Categories; Chemistry; Child; Childhood; Clinic Visits; Clinical; Clostridium difficile; Computer Retrieval of Information on Scientific Projects Database; Data; Databases; Diagnosis; Diarrhea; Diffuse; Disease; Disease remission; Dose; Double-Blind Method; Eligibility Determination; Endoscopy; Enrollment; Evaluation; Feces; Female; Fever; Frequencies; Funding; Genus Cola; Grant; Heart Rate; Height; Hematology; Hemorrhage; Hour; Inflammation; Inflammatory Bowel Diseases; Institution; Label; Laboratories; Lactoferrin; Leukocyte L1 Antigen Complex; Literature; Maintenance; Medical; Medical History; Mesalamine; Newly Diagnosed; Onset of illness; Ovum; Parasites; Patients; Pharmaceutical Preparations; Phase; Physical Examination; Population; Pregnancy Tests; Procedures; Protocols documentation; Randomized; Recording of previous events; Relapse; Research; Research Personnel; Resources; Safety; Sampling; Screening procedure; Serum; Severities; Severity of illness; Source; Symptoms; System; Tablets; Testing; Time; Ulcerative Colitis; United States; United States National Institutes of Health; Urinalysis; Urine; Weight; base; clinical practice; dosage; expectation; outcome forecast; pathogen; rectal; standard of care

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Ulcerative colitis (UC) is a type of inflammatory bowel disease characterized by diffuse, continuous inflammation of the colon. Recent estimates suggest that approximately 17,000children between 5 and 17 years of age in the U.S. are diagnosed with UC. Estimates of the average age at onset in children vary, although 80-90% of patients are 9 years of age or older when symptoms. Evidence from the medical literature suggests that the clinical course and manifestations of UC are similar in children and adults. The most consistent symptoms of UC (diarrhea, abdominal pain, rectal bleeding, fever, and weight loss) are found in comparable proportions in both children and adults with the disease, and are more dependent on the disease activity than age . In addition, in children and adults, extent of disease, which is sometimes used as an indicator of severity, does not necessarily predict disease activity or likelihood of surge, and there is little evidence that childhood onset of UC carries a worse prognosis than adult onset disease. 5-ASA products like Asacol used off-label as first-line therapy to treat children with UC. In children, Asacol 400 mg delayed-release mesalamine tablets are used in the United States (US) for the treatment of mildly-to- moderately active UC and for the maintenance of remission of UC. The currently indicated dosage for adults in the US for active UC is two 400 mg tablets taken 3 times a day (for a total daily dose of 2.4 grams) for 6 weeks. The purpose of this study is to assess the safety and efficacy of high dose and low dose Asacol administered as 400 mg delayed-release tablets given every 12 hours for 6 weeks to children and adolescents with mildly-to-moderately active ulcerative colitis. This is Phase III randomized, double-blind, parallel-group, 6-week study of 2 dose levels of Asacol consisting of a high dose and a low dose in pediatric patients ages 517 years. Randomization will be stratified by weight (17  33 kg, 33  54 kg, and 54  90 kg) and by disease severity (mild and moderate). High dose and low dose will be defined as follows for the 3 different weight groups. in the context of what is considered to be the current standard of care for pediatric UC patients (120 mg/kg/day). The high doses in each weight category (17  33 kg, 33  54 kg, and 54  90 kg) are approximately 1.67, 1.8 and 2 times the low dose, respectively. Patients will take study medication twice daily every 12 hours, at approximately the same time each day without regard to meals.Doses were selected based on the following considerations; clinical standard of care (not exceeding the maximum dose utilized in clinical practice of120 mg/kg/day); estimated local colonic/topical exposures; (see Appendix 7.6 for details).About 100 patients will be enrolled with the expectation that about 80 (40 combined high dose and 40 combined low dose) will complete. Patients must have a history of biopsy and endoscopy confirmed UC (either newly diagnosed or that has recently relapsed) with ongoing symptoms of mild to moderate UC to include both rectal bleeding and stool frequency. Patients will be treated with Asacol for 6 weeks with clinic visits for evaluation of safety, compliance, and efficacy at Baseline, Week 3, and Week 6. Sparse population PK samples will be obtained at Weeks 3 and 6. Disease activity in this study will be assessed using the following clinical symptom assessments: the validated PUCAI and a "Truncated Mayo" (TM-Mayo) assessment including the stool frequency and rectal bleeding domains of the Mayo scoring system. While endoscopies are not mandated by this protocol, data from any endoscopy that is performed for medical cause at the Investigator's discretion during the course of the study will be collected and entered into the study data base. Study Procedures: Medical history ;medication history; personal/demographic data; physical examination; body weight/height;vital signs (heart rate, blood pressure, body temperature); blood sample for hematology and serum chemistry tests (If a sample has been collected within 7 days of Screening at a local laboratory, these results may be used to determine patient eligibility; blood sample for serum biomarkers (lactoferrin and calprotectin). This will be done when core laboratory blood samples are drawn (either Screening or Baseline).The total volume of blood collected will be approximately 70 mL. Urine pregnancy test (post-menarchal females only); Note: The urine pregnancy test will be done using a pregnancy test kit provided by the central laboratory. urinalysis; stool sample for bacterial pathogens, ova and parasites, and C. difficile will also be collected.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 溃疡性结肠炎（UC）是一种以弥漫性为特征的炎症性肠病， 结肠的连续炎症。最近的估计表明大约 美国5至17岁之间的17,000儿童被诊断为UC。估计 尽管80-90％的患者年满9岁 症状时或年龄较大。医学文献的证据表明临床 在儿童和成人中，UC的课程和表现相似。最一致的 发现UC（腹泻，腹痛，直肠出血，发烧和体重减轻）的症状 在患有该疾病的儿童和成年人中，比例比例更高，并且更多 取决于疾病活动比年龄的活动。另外，在儿童和成人中， 疾病有时用作严重程度的指标，并不一定预测 疾病活动或激增的可能性，几乎没有证据表明UC的童年发作 与成人发作疾病相比，预后较差。 5-ASA产品（例如Asacol）使用了标签外 作为治疗UC儿童的一线疗法。在儿童中，Asacol 400毫克延迟释放 美赛胺片在美国（美国）使用 中度活跃的UC和维护UC的缓解。当前指示 美国成人的活性UC剂量为两片400毫克片剂，每天服用3次（对于 每日总剂量为2.4克）持续6周。 这项研究的目的是评估高剂量和低剂量曲霉的安全性和功效 每12小时给儿童每12小时给予400毫克延迟释放片 和青少年有轻度至模化的溃疡性结肠炎。 这是III期随机，双盲，平行组，6周研究2剂量水平的研究 小儿患者5 17岁的儿科患者中由高剂量和低剂量的曲菜组成。 随机分组将按重量（17 33千克，33 54千克和54 90千克）进行分层 疾病严重程度（轻度和中度）。高剂量和低剂量将定义如下 3个不同的体重组。 在被认为是当前标准的背景下 护理小儿UC患者（120 mg/kg/天）。每个体重类别的高剂量（17 33公斤，33 54公斤和54 90千克）约为1.67、1.8，低剂量的2倍，2倍 分别。患者每天每12小时两次接受学习药物，大约 每天同一时间不考虑餐点。根据以下内容选择了药 考虑因素；临床护理标准（不超过临床中使用的最大剂量 练习1120 mg/kg/day）；估计的局部结肠/局部暴露； （请参阅附录7.6 详细信息）。约有100名患者将被招募，预计约有80名患者（40个组合合并 高剂量和40个合并的低剂量）将完成。患者必须有活检病史 内窥镜检查证实了UC（新诊断或最近已经复发） 持续的轻度至中度UC的症状包括直肠出血和粪便 频率。患者将在诊所就诊中用asacol治疗6周，以评估 基线，第3周和第6周的安全性，合规性和功效。人口稀疏PK 样本将在第3和第6周获得。将评估这项研究的疾病活动 使用以下临床症状评估：经过验证的Pucai和“截断 Mayo”（TM-mayo）评估，包括粪便频率和直肠出血域 梅奥评分系统。尽管此协议未要求内窥镜，但 在调查员期间，由调查人员酌情执行的任何内窥镜检查 研究过程将被收集并进入研究数据库。研究程序： 病史；药物史；个人/人口统计数据；体格检查；身体 体重/身高；生命体征（心率，血压，体温）；血液样本 血液学和血清化学测试（如果在7天内收集样品 在当地实验室进行筛查，这些结果可用于确定患者资格。 血清生物标志物（乳铁蛋白和钙染色素）的血液样本。这将在核心时完成 绘制实验室血液样本（筛查或基线）。 收集的大约为70毫升。 尿液妊娠试验（仅在男结构后女性）； 注意：尿液妊娠检查将使用由妊娠试验套件进行 中央实验室。尿液分析；细菌病原体，OVA和寄生虫以及C.的粪便样品。 还将收集艰难梭菌。