Randomized controlled trial of KW-6356 monotherapy in patients with early untreated Parkinson's disease.
Adenosine
Adenosine antagonist
KW-6356
Monotherapy
Parkinson's disease
Journal
Parkinsonism & related disorders
ISSN: 1873-5126
Titre abrégé: Parkinsonism Relat Disord
Pays: England
ID NLM: 9513583
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
05
06
2023
revised:
17
10
2023
accepted:
23
10
2023
pubmed:
11
11
2023
medline:
11
11
2023
entrez:
10
11
2023
Statut:
ppublish
Résumé
KW-6356 is a novel selective adenosine A 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. 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). KW-6356 monotherapy is well tolerated and more effective than placebo in patients with early, untreated PD.
Identifiants
pubmed: 37948832
pii: S1353-8020(23)00986-0
doi: 10.1016/j.parkreldis.2023.105907
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
105907Investigateurs
Takashi Abe
(T)
Kentaro Deguchi
(K)
Kenichi Fujimoto
(K)
Kazuko Hasegawa
(K)
Hiroyuki Hatsuta
(H)
Nobutaka Hattori
(N)
Tatsuya Hattori
(T)
Shinichiro Ikebe
(S)
Yoshinori Ishida
(Y)
Mitsunori Ishikawa
(M)
Chiaki Isobe
(C)
Kazunori Ito
(K)
Mizuki Ito
(M)
Chikako Kaneko
(C)
Satoshi Kaneko
(S)
Naomi Kanzato
(N)
Noriko Kawashima
(N)
Takeshi Kitamura
(T)
Michio Kitayama
(M)
Takashi Kimura
(T)
Satoru Kosaka
(S)
Maeda Tetsuya
(M)
Hideki Mochizuki
(H)
Nobutoshi Morimoto
(N)
Miho Murata
(M)
Takashi Naka
(T)
Teruhiko Negishi
(T)
Yoshihiko Nishida
(Y)
Masahiro Nomoto
(M)
Satoshi Orimo
(S)
Hidemoto Saiki
(H)
Mayumi Sakata
(M)
Akira Sato
(A)
Yasushi Shimo
(Y)
Keisuke Suzuki
(K)
Ryosuke Takahashi
(R)
Atsushi Takeda
(A)
Yoshihisa Tatsuoka
(Y)
Kazuo Toda
(K)
Masahiko Tomiyama
(M)
Shuta Toru
(S)
Yoshio Tsuboi
(Y)
Akira Tsujino
(A)
Takenori Uozumi
(T)
Hitoshi Yamada
(H)
Mitsutoshi Yamamoto
(M)
Kazuto Yoshida
(K)
Junji Yoshinaga
(J)
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest Tetsuya Maeda was the responsible medical officer for the study and reports receiving personal fees from Kyowa Kirin Co., Ltd. Takashi Kimura was a study investigator and Nobutaka Hattori was the coordinating investigator; both report receiving personal fees from Kyowa Kirin Co., Ltd. Kenichiro Sugiyama, Kana Yamada, Ren Hiraiwa and Masato Nishi are employed by Kyowa Kirin Co., Ltd.