A MULTICENTER, DOSE RANGING SAFETY AND PHARMACOKINETICS STUDY OF ARIMOCLOMOL IN)

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这是一项由研究者发起、行业赞助的IIA期双盲研究，旨在评估三种剂量水平的Arimoclomol的安全性、耐受性和CSF渗透性。 将来自8至10个中心的80名受试者随机分为四组之一：安慰剂组、Arimoclomol 25 mg t.i.d.组、50 mg，每日3次或100 mg t.i.d.并接受为期12周的研究药物治疗。治疗4周后，一部分研究受试者（约一半或40名）将进入机构GCRC进行血清和CSF药代动力学研究。将在第8周和第12周进行额外的随访访视。将进行为期4周的治疗后安全性评估。基于安全性和药代动力学数据，将评估哪些剂量是安全的以及CSF中各自的药物水平。 将决定IIb期研究的两种最佳剂量。IIA期研究的研究参与者将可以选择开放标签扩展研究。将编写单独的开放标签扩展方案并提交给研究中心IRB。 可靠性测试 为了评估肺活量测试的评定者可靠性，每个研究中心将入组3 - 5例ALS受试者。 这些受试者可能也可能不参加IIa期研究。 每名受试者将接受两次测试，间隔30分钟至一周。 参与可靠性测试的受试者必须年满18岁，身体能够进行肺活量测试，并诊断为ALS。 将从参与可靠性试验的每例受试者处获得单独的知情同意书。 临床试验机构数量 本研究将在美国的8至10个东北ALS联盟（NEALS）ALS中心进行，这些中心的入选是因为其招募记录良好、符合研究方案和法规、临床研究专业知识和资源。 的受试者数量 80例受试者将随机接受治疗;每个治疗组20例受试者（安慰剂、75、150和300 mg/天）。 将在UCI筛选15例患者参加本试验;本试验将招募10例患者。所有10例患者将参加药代动力学研究。 估计研究持续时间 预计入组持续时间约为12周。 对于每例参与受试者，将进行12周的强化评价和4周的随访。 预计个体受试者的整个试验持续时间约为19周（入组、合格性评价和16周随访）。 研究程序 评估时间表 评估时间表概述了每次研究访视时要完成的所有研究程序（图1）。访视必须在计划访视的+/-3天内完成。提前终止研究的患者必须完成第12周和第16周描述的所有程序。

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. This is an investigator-initiated industry-sponsored phase IIA double-blind study designed to assess the safety, tolerability and CSF penetration of three dose levels of Arimoclomol. Eighty subjects from eight to ten centers will be randomized to one of four groups: placebo, Arimoclomol 25 mg t.i.d., 50 mg t.i.d. or 100 mg t.i.d. and receive study medication for 12 weeks. After four weeks of treatment, a subset of research participants (approximately half, or 40) will be admitted to the institutional GCRC for a serum and CSF pharmacokinetic study. Additional follow-up visits will occur at 8 and 12 weeks. There will be a 4-week post-treatment safety assessment. Based on both the safety and the pharmacokinetic data, an assessment will be made as to which dosages are safe and their respective drug levels in CSF. A decision will be made as to the best two dosages for the phase IIb study. Research participants in the phase IIA study will be given the option for open-label extension study. The separate open label extension protocol will be written and submitted to the site IRBs. Reliability Testing To assess rater reliability for vital capacity testing 3 to 5 subjects with ALS will be enrolled per study site. These subjects may or may not also participate in the phase IIa study. Each subject will be tested two times separated by 30 minutes to one week. Subjects participating in reliability testing must be at least 18 years of age, physically able to perform vital capacity testing and have a diagnosis of ALS. Separate informed consent will be obtained from each subject participating in reliability testing. Number of Centers This study will be conducted in the U.S. at eight to ten Northeast ALS Consortium (NEALS) ALS centers, selected because of their excellent records of recruitment, compliance with study protocols and regulations, clinical research expertise and resources. Number of Subjects Eighty subjects will be randomized to receive treatment; 20 subjects per treatment group (placebo, 75, 150 and 300 mg/day). Fifteen (15) patients will be screened for this trial at UCI; 10 patients will be recruited for this trial. All ten patients will participate in the pharmacokinetics study. Estimated Study Duration The duration of enrollment is expected to be approximately 12 weeks. For each participating subject there will be 12 weeks of intensive evaluation and 4 weeks of follow-up. The entire duration of the trial for individual subjects is anticipated to be approximately 19 weeks (enrollment, eligibility evaluation, and 16 weeks follow-up). Study Procedures Schedule of Assessments The Schedule of Assessments outlines all study procedures to be completed at each study visit (Figure 1). Visits must be completed within +/-3 days of the scheduled visit. Patients who discontinue the study prematurely must complete all procedures described under weeks 12 and 16.