KW-6356单药治疗早期未经治疗帕金森病患者的随机对照试验。

Randomized controlled trial of KW-6356 monotherapy in patients with early untreated Parkinson's disease.

作者信息

Maeda Tetsuya, Kimura Takashi, Sugiyama Kenichiro, Yamada Kana, Hiraiwa Ren, Nishi Masato, Hattori Nobutaka

机构信息

Division of Neurology and Gerontology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Iwate, Japan.

Department of Neurology, Asahikawa Medical Center, Hokkaido, Japan.

出版信息

Parkinsonism Relat Disord. 2023 Dec;117:105907. doi: 10.1016/j.parkreldis.2023.105907. Epub 2023 Oct 31.

DOI:10.1016/j.parkreldis.2023.105907

PMID:37948832

Abstract

INTRODUCTION

KW-6356 is a novel selective adenosine A receptor antagonist/inverse agonist. We evaluated the efficacy and safety of KW-6356 as monotherapy in patients with early, untreated Parkinson's disease (PD).

METHODS

This was a randomized, placebo-controlled, double-blind study conducted in Japan to investigate the efficacy and safety of once-daily KW-6356 (3 or 6 mg/day) orally administered as monotherapy for 12 weeks in patients with early PD (NCT02939391). The primary endpoint was the least squares means of change from baseline in the MDS-UPDRS Part III total score.

RESULTS

Overall, 168 patients were randomized and treated (KW-6356 3 mg/day n = 55; 6 mg/day n = 58, placebo n = 55); Week 12 completion rates were >90% per group. LS mean [95% CI] changes from baseline to Week 12 in MDS-UPDRS Part III total scores were -5.37 [-7.25, -3.48] for 3 mg/day, -4.76 [-6.55, -2.96] for 6 mg/day and -3.14 [-4.97, -1.30] for placebo. Changes from baseline were larger for both KW-6356 groups than for the placebo group at all time points. Secondary endpoints supported the primary findings with larger changes in MDS-UPDRS Part II, Parts II + III, and Total scores in the KW-6356 groups than in the placebo group. Treatment was well-tolerated; the most common treatment-emergent adverse events with KW-6356 were constipation (n = 4 [7.3%] and n = 6 [10.3%] in the 3 and 6 mg/day groups, respectively) followed by nasopharyngitis (n = 4 [7.3%] and n = 5 [8.6%] in the 3 and 6 mg/day groups, respectively).

CONCLUSION

KW-6356 monotherapy is well tolerated and more effective than placebo in patients with early, untreated PD.

摘要

引言

KW-6356是一种新型的选择性腺苷A受体拮抗剂/反向激动剂。我们评估了KW-6356作为单一疗法治疗早期未经治疗的帕金森病（PD）患者的疗效和安全性。

方法

这是一项在日本进行的随机、安慰剂对照、双盲研究，旨在调查每日一次口服KW-6356（3或6毫克/天）作为单一疗法治疗早期PD患者12周的疗效和安全性（NCT02939391）。主要终点是MDS-UPDRS第三部分总分相对于基线变化的最小二乘均值。

结果

总体而言，168例患者被随机分组并接受治疗（KW-6356 3毫克/天组n = 55；6毫克/天组n = 58，安慰剂组n = 55）；每组第12周的完成率均>90%。从基线到第12周，MDS-UPDRS第三部分总分的最小二乘均值[95%置信区间]变化在3毫克/天组为-5.37[-7.25，-3.48]，6毫克/天组为-4.76[-6.55，-2.96]，安慰剂组为-3.14[-4.97，-1.30]。在所有时间点，KW-6356两个组相对于基线的变化均大于安慰剂组。次要终点支持了主要研究结果，KW-6356组在MDS-UPDRS第二部分、第二部分+第三部分以及总分方面的变化大于安慰剂组。治疗耐受性良好；KW-6356最常见的治疗中出现不良反应是便秘（3毫克/天组n = 4[7.3%]，6毫克/天组n = 6[10.3%]），其次是鼻咽炎（3毫克/天组n = 4[7.3%]，6毫克/天组n = 5[8.6%]）。