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Abstract：
Open-HART was an open-label extension of HART, a randomized, double-blind, placebo-controlled study of pridopidine in Huntington disease (HD). Previously, we reported safety and exploratory efficacy data after 36 months of treatment with pridopidine 45 mg twice daily. In the interim, emerging data suggests pridopidine may have neuroprotective effects mediated by sigma-1 receptor agonism.
To report additional safety and exploratory efficacy data for continued open-label use of 45 mg BID pridopidine at 48 and 60 months.
Patients in Open-HART were followed up to or greater than 60 months. Adverse events, concomitant medications, vital signs, laboratory values, and ECG data were monitored. Rates of decline in total functional capacity (TFC) and total motor score (TMS) over 60 months were evaluated in an exploratory analysis and compared between Open-HART and placebo recipients from the 2CARE trial. To account for missing data, sensitivity analyses were performed.
Of the original Open-HART baseline cohort (N = 118), 40 remained in the study at 48 months and 33 at 60 months. Pridopidine remained safe and well tolerated over the 60-month interval. TFC and TMS at 48 and 60 months remained stable, showing less decline at these timepoints compared to historical placebo controls from the 2CARE trial. TFC differences at 48 and 60 months observed remained nominally significant after sensitivity analysis.
The 45 mg BID pridopidine dosage remained safe and tolerable over 60 months. Exploratory analyses show TFC and TMS stability at 48 and 60 months, in contrast to placebo historical controls from the 2CARE trial. Results are consistent with data reported from the recent Phase 2 PRIDE-HD trial showing less functional decline in the pridopidine 45 mg BID treated group at 52 weeks.
To report additional safety and exploratory efficacy data for continued open-label use of 45 mg BID pridopidine at 48 and 60 months.
Patients in Open-HART were followed up to or greater than 60 months. Adverse events, concomitant medications, vital signs, laboratory values, and ECG data were monitored. Rates of decline in total functional capacity (TFC) and total motor score (TMS) over 60 months were evaluated in an exploratory analysis and compared between Open-HART and placebo recipients from the 2CARE trial. To account for missing data, sensitivity analyses were performed.
Of the original Open-HART baseline cohort (N = 118), 40 remained in the study at 48 months and 33 at 60 months. Pridopidine remained safe and well tolerated over the 60-month interval. TFC and TMS at 48 and 60 months remained stable, showing less decline at these timepoints compared to historical placebo controls from the 2CARE trial. TFC differences at 48 and 60 months observed remained nominally significant after sensitivity analysis.
The 45 mg BID pridopidine dosage remained safe and tolerable over 60 months. Exploratory analyses show TFC and TMS stability at 48 and 60 months, in contrast to placebo historical controls from the 2CARE trial. Results are consistent with data reported from the recent Phase 2 PRIDE-HD trial showing less functional decline in the pridopidine 45 mg BID treated group at 52 weeks.
摘要：
Open-HART是HART的开放标签扩展,一个随机的，双盲,普利多匹定治疗亨廷顿病（HD）的安慰剂对照研究。以前,我们报告了普利多匹定45mg每日2次治疗36个月后的安全性和探索性疗效数据.在此期间，新出现的数据表明普利多匹定可能具有sigma-1受体激动介导的神经保护作用。
报告在48个月和60个月时继续开放标签使用45mgBID普利多匹定的其他安全性和探索性疗效数据。
Open-HART患者随访至或大于60个月。不良事件,合并用药,生命体征,实验室值，并监测心电图数据。在探索性分析中评估了60个月内总功能能力（TFC）和总运动评分（TMS）的下降率，并比较了2CARE试验的Open-HART和安慰剂接受者。为了解决丢失的数据，进行了敏感性分析。
在原始Open-HART基线队列中（N=118），40在48个月时仍在研究中，33在60个月时仍在研究中。在60个月的间隔内，普利多匹定仍然安全且耐受性良好。TFC和TMS在48和60个月时保持稳定，与2CARE试验的历史安慰剂对照相比，在这些时间点显示出更少的下降。在敏感性分析后，观察到的48和60个月的TFC差异在名义上仍然显着。
45mgBID普利多匹定剂量在60个月内保持安全和耐受。探索性分析显示TFC和TMS在48和60个月时的稳定性，与来自2CARE试验的安慰剂历史对照相反.结果与最近的2期PRIDE-HD试验报告的数据一致，显示普利多匹定45mgBID治疗组在52周时功能下降较少。
报告在48个月和60个月时继续开放标签使用45mgBID普利多匹定的其他安全性和探索性疗效数据。
Open-HART患者随访至或大于60个月。不良事件,合并用药,生命体征,实验室值，并监测心电图数据。在探索性分析中评估了60个月内总功能能力（TFC）和总运动评分（TMS）的下降率，并比较了2CARE试验的Open-HART和安慰剂接受者。为了解决丢失的数据，进行了敏感性分析。
在原始Open-HART基线队列中（N=118），40在48个月时仍在研究中，33在60个月时仍在研究中。在60个月的间隔内，普利多匹定仍然安全且耐受性良好。TFC和TMS在48和60个月时保持稳定，与2CARE试验的历史安慰剂对照相比，在这些时间点显示出更少的下降。在敏感性分析后，观察到的48和60个月的TFC差异在名义上仍然显着。
45mgBID普利多匹定剂量在60个月内保持安全和耐受。探索性分析显示TFC和TMS在48和60个月时的稳定性，与来自2CARE试验的安慰剂历史对照相反.结果与最近的2期PRIDE-HD试验报告的数据一致，显示普利多匹定45mgBID治疗组在52周时功能下降较少。
