INTRODUCTION CVT-301 is an orally inhaled levodopa therapy approved for the intermittent treatment of OFF episodes in Parkinson's disease patients who are taking a standard oral levodopa regimen. This open-label, randomized, controlled study over 12 months characterizes the safety, including pulmonary safety, of CVT-301 84 mg (nominal respirable levodopa fine-particle dose, 50 mg). METHODS Patients experiencing motor fluctuations were randomized 2:1 to CVT-301 or an observational cohort (OC) receiving oral standard of care. Pulmonary safety was assessed using spirometry and carbon monoxide diffusion capacity (DLCO). Exploratory efficacy endpoints, assessed only for CVT-301, included change in Unified Parkinson's Disease Rating Scale Part III (UPDRS-III), patients achieving ON within 60 min and remaining ON at 60 min, Patient Global Impression of Change (PGIC) scale, and total daily OFF time. RESULTS Of 408 patients randomized, 310 completed the study (204 in CVT-301 and 106 in OC). Mean 12-month changes from baseline for CVT-301 were -0.105 L (FEV1) and -0.378 mL/min/mm Hg (DLCO), and for OC were -0.117 L and -0.722 mL/min/mm Hg, respectively. Between-group comparisons were not statistically significant. For FEV1/FVC the 12-month change was -0.3 and -1.6, respectively, which was a significant between-group difference. However, between-group differences were not significant at 3 and 9 months and all changes from baseline were small (<2.0%). UPDRS-III scores improved from predose to 60 min postdose at all assessments; 80%-85% of patients switched ON within 60 min and remained ON; and >75% reported improvement in PGIC. OFF time decreased by 1.32-1.42 h/day. CONCLUSION CVT-301 84 mg induced no clinically significant differences in pulmonary function compared with the OC. Improvements in motor scores, OFF time, and patient-reported outcomes support clinical efficacy for up to 12 months.

中文翻译：

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帕金森氏病处于关闭期的患者吸入左旋多巴：一项为期12个月的随机肺安全性研究。

简介CVT-301是一种口服吸入的左旋多巴疗法，已批准用于间歇性治疗接受标准口服左旋多巴疗法的帕金森氏病患者的OFF发作。这项为期12个月的开放标签，随机对照研究确定了CVT-301 84 mg（标称可吸入左旋多巴微粒剂量50 mg）的安全性，包括肺部安全性。方法将运动波动患者按2：1的比例随机分配至CVT-301或接受口服标准护理的观察性队列（OC）。使用肺活量测定法和一氧化碳扩散能力（DLCO）评估肺安全性。仅针对CVT-301进行评估的探索性疗效终点包括帕金森病疾病统一评估量表第III部分（UPDRS-III）的变化，患者在60分钟内达到ON并在60分钟时保持ON，患者总体变化印象（PGIC）量表和每日总关闭时间。结果在408例患者中，有310例完成了研究（CVT-301中为204例，OC中为106例）。CVT-301与基线相比的平均12个月变化分别是-0.105 L（FEV1）和-0.378 mL / min / mm Hg（DLCO），而OC分别是-0.117 L和-0.722 mL / min / mm Hg。组间比较无统计学意义。FEV1 / FVC的12个月变化分别为-0.3和-1.6，这是组间的显着差异。但是，组间差异在3个月和9个月时并不显着，并且所有与基线相比的变化均很小（<2.0％）。在所有评估中，UPDRS-III评分从用药前提高到用药后60分钟；80％-85％的患者在60分钟内打开并保持打开状态；> 75％的受访者表示PGIC有改善。关闭时间减少了1.32-1。42小时/天。结论CVT-301 84 mg与OC相比，在肺功能方面无临床显着差异。运动评分，关闭时间和患者报告结果的改善可支持长达12个月的临床疗效。