McGarry Andrew, Kieburtz Karl, Abler Victor, Grachev Igor D, Gandhi Sanjay, Auinger Peggy, Papapetropoulos Spyridon, Hayden Michael
Cooper University Health Care at Rowan University, Camden, NJ, USA.
University of Rochester Medical Center, Rochester, NY, USA.
J Huntingtons Dis. 2017;6(3):189-199. doi: 10.3233/JHD-170241.
Open-HART is an open-label extension of HART, a randomized, placebo-controlled, dose-ranging, parallel-group study.
To evaluate safety and exploratory efficacy of open-label pridopidine over 36 months in subjects with Huntington's disease (HD).
Open-HART subjects were treated with pridopidine 45 mg twice daily (BID). After initial evaluation by telephone (Week 1) and in person (Month 1), in-person visits occurred every 3 months, alternating between safety and clinical visits (safety plus Unified Huntington's Disease Rating Scale [UHDRS] assessment). The UHDRS was performed for pre-specified analysis as a secondary outcome measure. Adverse events (AEs), laboratory values, and electrocardiography were monitored throughout.
Most subjects (89%) reported at least one AE, with 30% experiencing treatment-related AEs. The most common AEs during the first year were falls (12.7%), anxiety (9.3%), insomnia (8.5%), irritability (6.8%), and depression (5.9%). Ninety-nine percent of subjects took concomitant medications. Two seizures were reported as AEs. No arrhythmias or suicide attempts were reported. Five deaths occurred, all considered treatment unrelated. Secondary exploratory analyses of subjects on pridopidine demonstrated motor deterioration (as measured by the UHDRS total motor score) consistent with HD's natural history, as shown in large observational studies. A post-hoc, exploratory analysis of TFC performance compared to placebo groups from other long-term HD studies demonstrated no significant effect for pridopidine on TFC progression after correction for multiple comparisons.
Pridopidine 45 mg BID was generally safe and tolerable in HD subjects over 36 months. TMS declined in a manner consistent with the known natural history of HD.
Open-HART是HART的开放标签扩展研究，HART是一项随机、安慰剂对照、剂量范围、平行组研究。
评估开放标签的普立多匹定在亨廷顿舞蹈症（HD）患者中36个月的安全性和探索性疗效。
Open-HART研究的受试者接受每日两次、每次45毫克的普立多匹定治疗。在通过电话（第1周）和亲自就诊（第1个月）进行初始评估后，每3个月进行一次亲自就诊，安全访视和临床访视交替进行（安全访视加上统一亨廷顿舞蹈症评定量表[UHDRS]评估）。UHDRS作为次要结局指标进行预先指定的分析。全程监测不良事件（AE）、实验室检查值和心电图。
大多数受试者（89%）报告至少发生过一次AE，30%经历了与治疗相关的AE。第一年最常见的AE是跌倒（12.7%）、焦虑（9.3%）、失眠（8.5%）、易怒（6.8%）和抑郁（5.9%）。99%的受试者服用了伴随药物。报告了两例癫痫发作作为AE。未报告心律失常或自杀企图。发生了5例死亡，均认为与治疗无关。对服用普立多匹定的受试者进行的二次探索性分析显示，运动功能恶化（通过UHDRS总运动评分衡量）与HD的自然病程一致，如大型观察性研究所示。与其他长期HD研究的安慰剂组相比，对TFC表现进行的事后探索性分析显示，在进行多重比较校正后，普立多匹定对TFC进展无显著影响。
每日两次服用45毫克普立多匹定在HD受试者中36个月内总体上是安全且可耐受的。TMS以与HD已知自然病程一致的方式下降。
