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Abstract：
No pharmacological treatment has been demonstrated to provide a functional benefit for persons with Huntington\'s disease (HD). Pridopidine is a sigma-1-receptor agonist shown to have beneficial effects in preclinical models of HD.
To further explore the effect of pridopidine on Total Functional Capacity (TFC) in the recent double-blind, placebo-controlled PRIDE-HD study.
We performed post-hoc analyses to evaluate the effect of pridopidine on TFC at 26 and 52 weeks. Participants were stratified according to baseline TFC score and analyzed using repeated measures (MMRM) and multiple imputation assuming missing not-at-random (MNAR) and worst-case scenarios.
The pridopidine 45 mg bid dosage demonstrated a beneficial effect on TFC for the entire population at week 52 of 0.87 (nominal p = 0.0032). The effect was more pronounced for early HD participants (HD1/HD2, TFC = 7-13), with a change from placebo of 1.16 (nominal p = 0.0003). This effect remained nominally significant using multiple imputation with missing not at random assumption as a sensitivity analysis. Responder analyses showed pridopidine 45 mg bid reduced the probability of TFC decline in early HD patients at Week 52 (nominal p = 0.02).
Pridopidine 45 mg bid results in a nominally significant reduction in TFC decline at 52 weeks compared to placebo, particularly in patients with early-stage HD.
To further explore the effect of pridopidine on Total Functional Capacity (TFC) in the recent double-blind, placebo-controlled PRIDE-HD study.
We performed post-hoc analyses to evaluate the effect of pridopidine on TFC at 26 and 52 weeks. Participants were stratified according to baseline TFC score and analyzed using repeated measures (MMRM) and multiple imputation assuming missing not-at-random (MNAR) and worst-case scenarios.
The pridopidine 45 mg bid dosage demonstrated a beneficial effect on TFC for the entire population at week 52 of 0.87 (nominal p = 0.0032). The effect was more pronounced for early HD participants (HD1/HD2, TFC = 7-13), with a change from placebo of 1.16 (nominal p = 0.0003). This effect remained nominally significant using multiple imputation with missing not at random assumption as a sensitivity analysis. Responder analyses showed pridopidine 45 mg bid reduced the probability of TFC decline in early HD patients at Week 52 (nominal p = 0.02).
Pridopidine 45 mg bid results in a nominally significant reduction in TFC decline at 52 weeks compared to placebo, particularly in patients with early-stage HD.
摘要：
尚未证明药物治疗可为亨廷顿氏病（HD）患者提供功能益处。Pridopidine是sigma-1受体激动剂，在HD的临床前模型中具有有益作用。
为了进一步探索普利多匹定对近期双盲研究中总功能容量（TFC）的影响，安慰剂对照PRIDE-HD研究。
我们在26周和52周时进行事后分析以评估普利多匹定对TFC的影响。根据基线TFC评分对参与者进行分层，并使用重复测量（MMRM）和多重插补进行分析，假设缺少非随机（MNAR）和最坏情况。
普利多匹定45mgbid剂量在第52周时对整个人群的TFC显示出有益的作用为0.87(标称p=0.0032)。对于早期HD参与者（HD1/HD2，TFC=7-13），与安慰剂的变化为1.16（名义p=0.0003）。使用多重插补作为敏感性分析，这种效果在名义上仍然显着，而不是随机假设。响应者分析显示，普利多匹定45mgbid降低了第52周早期HD患者TFC下降的可能性（名义p=0.02）。
与安慰剂相比，普利多匹定45mgbid导致52周时TFC下降的名义上显著减少，尤其是早期HD患者。
为了进一步探索普利多匹定对近期双盲研究中总功能容量（TFC）的影响，安慰剂对照PRIDE-HD研究。
我们在26周和52周时进行事后分析以评估普利多匹定对TFC的影响。根据基线TFC评分对参与者进行分层，并使用重复测量（MMRM）和多重插补进行分析，假设缺少非随机（MNAR）和最坏情况。
普利多匹定45mgbid剂量在第52周时对整个人群的TFC显示出有益的作用为0.87(标称p=0.0032)。对于早期HD参与者（HD1/HD2，TFC=7-13），与安慰剂的变化为1.16（名义p=0.0003）。使用多重插补作为敏感性分析，这种效果在名义上仍然显着，而不是随机假设。响应者分析显示，普利多匹定45mgbid降低了第52周早期HD患者TFC下降的可能性（名义p=0.02）。
与安慰剂相比，普利多匹定45mgbid导致52周时TFC下降的名义上显著减少，尤其是早期HD患者。
