Enteric-Coated Oral Beclomethasone Dipropionate in Patients with Acute Enteritis

肠溶口服二丙酸倍氯米松治疗急性肠炎

• 批准号: 7748859
• 负责人: Christopher Joseph Schaber
• 金额: $ 25.12万
• 依托单位: SOLIGENIX, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-03 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7748859
• 关键词: Abdomen; Abdominal Pain; Acute; Address; Adrenal Cortex Hormones; Adverse effects; Affect; Anorexia; Applications Grants; Beclomethasone Dipropionate; Biological Availability; Breathing; Cells; Cessation of life; Chronic; Clinical; Clinical Research; Clinical Trials; Colon; Cushingoid habitus; Data; Deglutition; Development; Diarrhea; Dose; Dose Fractionation; Dose-Limiting; Drug Kinetics; Enrollment; Enteral; Enteric-Coated Tablets; Exposure to; External Beam Radiation Therapy; Feedback; Frequencies; Funding; Gastrointestinal tract structure; Glucocorticoids; Glucose Intolerance; Goals; Incidence; Infection; Inflammatory; Inflammatory disease of the intestine; Interruption; Intestines; Lower Gastrointestinal Tract; Malignant Neoplasms; Maximum Tolerated Dose; Medical; Methylprednisolone; Modification; Monitor; Mucous Membrane; Muscle Weakness; Natural History; Normal Cell; Oral; Oral Administration; Pain; Patients; Pelvis; Pharmaceutical Preparations; Pharmacology; Phase; Phase I Clinical Trials; Plasma; Population; Positioning Attribute; Prednisone; Prevention; Principal Investigator; Process; Program Development; Protocols documentation; Quality of life; Radiation; Radiation Enteritis; Radiation therapy; Rectal Cancer; Reporting; Request for Applications; Review Literature; Risk; Safety; Schedule; Severities; Signs and Symptoms; Small Business Innovation Research Grant; Symptoms; Techniques; Therapeutic; Time; Toxic effect; Treatment Protocols; Ulcer; Visit; Vomiting; absorption; base; bone fatigue; cancer therapy; chemotherapy; clinically significant; cohort; demineralization; design; diaries; enteritis; follow up assessment; gastrointestinal; ileum; irradiation; open label; patient population; prevent; programs; prophylactic; public health relevance; research clinical testing; response

DESCRIPTION (provided by applicant): Acute radiation enteritis is caused by radiation-induced death of the normal cells in the lining of the bowel. As bowel cells die and are not replaced, gastrointestinal toxicity develops over the next few days and weeks with chronic diarrhea, vomiting and pain being the major symptoms. The addition of chemotherapy often exacerbates the onset, severity, and debilitation related to intestinal symptoms. Radiation enteritis often results in delay or interruption of the cancer treatment. There are over 100,000 patients who receive abdominal or pelvic external beam radiation treatment for cancer in the US. These patients are at risk of developing acute and chronic radiation enteritis. The proposed study is a multicenter, open-label, sequential, dose-escalation, Phase 1/2 clinical trial. Up to 48 subjects will be enrolled in four groups. Each dose level will be completed and the first cycle of treatment determined to be safe prior to administration at the next dose level. Emergent signs and symptoms referable to the GI tract, AEs, and concomitant medications will be recorded in all patients enrolled throughout RT and up to the study visit at 4-weeks post-RT, or until the patient is withdrawn earlier from the study, and will be reviewed for assessment of DLT. The safety results will be reviewed by the Principal Investigator(s) (PIs) and the DOR Medical Monitor. Any clinically significant anomaly or change from baseline will be noted. If dose escalation is not permitted, the preceding dose level will be considered the MTD. There will be no expansion of the patient cohort at the DLT. Key endpoints being evaluated include, but are not limited to: 1. dose-limiting toxicity; 2. maximum tolerated dose; 3. incidence and severity of AEs probably related (i.e., probably and highly probably related) to study treatment; 4. grade of gastrointestinal toxicity; and 5. duration of RT emergent diarrhea as assessed by subject diary. At the completion of the trial DOR intends to evaluate the data generated with the intent of designing additional clinical studies to demonstrate the safety and efficacy of DOR201 for the prevention of acute radiation enteritis. PUBLIC HEALTH RELEVANCE: This grant application requests funding to initiate (via a Phase 1/2 clinical study) the clinical evaluation of DOR201, enteric-coated oral beclomethasone dipropionate (BDP) for use in preventing acute radiation enteritis in patients undergoing radiation and chemotherapy for rectal cancer. The development of acute radiation enteritis significantly impacts the patient's quality of life and may result in modification of the cancer treatment. Based on the pharmacology of BDP, DOR201 has the potential to prevent the onset of acute radiation enteritis thereby addressing an important unmet medical need. Upon completion of the proposed clinical study, DOR intends to evaluate the data generated with the intent on designing additional clinical studies to demonstrate both the safety and efficacy of DOR201 for the prevention of acute radiation enteritis.

描述（由申请人提供）： 急性放射性肠炎是由辐射引起肠壁正常细胞死亡引起的。由于肠细胞死亡且未被替换，在接下来的几天和几周内会出现胃肠道毒性，主要症状是慢性腹泻、呕吐和疼痛。添加化疗通常会加剧与肠道症状相关的发作、严重程度和衰弱。放射性肠炎常常导致癌症治疗的延迟或中断。在美国，有超过 100,000 名患者接受腹部或盆腔外束放射治疗癌症。这些患者有患急性和慢性放射性肠炎的风险。拟议的研究是一项多中心、开放标签、序贯、剂量递增、1/2 期临床试验。最多 48 名受试者将被分为四组。每个剂量水平将完成，并且在下一个剂量水平给药之前确定第一个治疗周期是安全的。所有患者在整个 RT 期间和 RT 后 4 周的研究访视期间，或直到患者提前退出研究，都将记录与胃肠道、AE 和伴随药物相关的紧急体征和症状，并将接受 DLT 评估审查。安全性结果将由首席研究员 (PI) 和 DOR 医疗监察员进行审查。任何临床上显着的异常或相对于基线的变化都会被记录下来。如果不允许剂量递增，则之前的剂量水平将被视为 MTD。 DLT 的患者群体不会扩大。正在评估的关键终点包括但不限于： 1. 剂量限制性毒性； 2.最大耐受剂量； 3. AE 的发生率和严重程度可能与研究治疗相关（即可能和高度可能相关）； 4.胃肠道毒性分级； 5.通过受试者日记评估的 RT 突发腹泻的持续时间。试验完成后，DOR 打算评估生成的数据，旨在设计额外的临床研究，以证明 DOR201 预防急性放射性肠炎的安全性和有效性。公共健康相关性：本拨款申请请求资金启动（通过 1/2 期临床研究）DOR201 的临床评估，DOR201 是肠溶口服二丙酸倍氯米松 (BDP)，用于预防接受直肠癌放疗和化疗的患者的急性放射性肠炎。急性放射性肠炎的发展显着影响患者的生活质量，并可能导致癌症治疗的改变。基于 BDP 的药理学，DOR201 有潜力预防急性放射性肠炎的发作，从而解决重要的未满足的医疗需求。完成拟议的临床研究后，DOR 打算评估生成的数据，旨在设计额外的临床研究，以证明 DOR201 预防急性放射性肠炎的安全性和有效性。