Zonisamide improves wearing-off in Parkinson's disease: A randomized, double-blind study

Miho Murata, Kazuko Hasegawa, Ichiro Kanazawa, Junichi Fukasaka, Kenji Kochi, Rieko Shimazu, Takashi Kimura, Kazuto Yoshida, Seiji Kikuchi, Masayuki Baba, Keiji Chida, Kimiaki Utsugizawa, Takashi Abe, Atsushi Takeda, Toru Kawanami, Shunsuke Kobayashi, Kazuo Yoshizawa, Akira Tamaoka, Kenichi Fujimoto, Koichi OkamotoMasabuchi Ryo, Daisuke Uematsu, Masato Asahina, Hideji Hashida, Shinichiro Uchiyama, Norihiro Suzuki, Hiroya Utsumi, Satoshi Orimo, Masashi Takanashi, Hidehiro Mizusawa, Yu Kono, Tomoko Okamoto, Fusako Yokochi, Hideki Takubo, Satoe Matsubayashi, Teruo Yokoyama, Tsugio Akutsu, Hideki Mochizuki, Fumihito Yoshii, Makoto Shiraishi, Mieko Ogino, Hitoshi Yamada, Noriko Kawashima, Yasuhiro Kawase, Makoto Yoneda, Yoshihisa Takiyama, Takao Hashimoto, Hiroaki Miyajima, Yasuyuki Okuma, Koichi Mizoguchi, Tatsuya Hattori, Mitsunori Ishikawa, Yoshihisa Tatsuoka, Hidemoto Saiki, Tomonobu Kato, Harutoshi Fujimura, Yoshiyuki Mitsui, Yusaku Nakamura, Yasufumi Kageyama, Koji Kajiyama, Kazuo Toda, Yo Nishimura, Toshihiko Suenaga, Ichiro Nakanishi, Yoshihiko Nishida, Masahiro Nagai, Tomoaki Yuhi, Takenori Uozumi, Akira Sato, Hidenori Matsuo, Kazuhito Tsuruta, Hideya Matsumoto, Tatsui Nagado

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Background: Previously, we reported 50 mg/d zonisamide improved wearing-off without increasing dyskinesia in patients with Parkinson's disease (PD). Methods: To determine the efficacy of zonisamide for treatment of "off" time in PD patients, we conducted a multicenter, randomized, double-blind, parallel-group, placebo-controlled study in Japan. Patients with PD and wearing-off received placebo for 4 weeks and then were treated for 12 weeks with zonisamide 25 or 50 mg/d or placebo, in addition to their previous therapy. The primary endpoint was the change from baseline in daily "off" time as determined by patients' diaries at the final assessment. Secondary endpoints included changes from baseline in the total scores of the Unified Parkinson's Disease Rating Scale Parts I, II, III, and IV, the dyskinesia duration, and PDQ-39 score. Results: Of 422 patients enrolled, 389 (131 for placebo, 130 for zonisamide 25 mg, and 128 for zonisamide 50 mg) were randomized, and 354 (120, 119, and 115, respectively) completed the study. The "off" time significantly reduced by 0.719±0.179 h for zonisamide, 50 mg compared with placebo (0.011±0.173 h, P=0.005). Although the incidence of somnolence was higher for zonisamide (3.1% for zonisamide 25 mg, 6.3% for zonisamide 50 mg) than for placebo (2.3%), the incidences of the other adverse events, including dyskinesia or hallucination, for both zonisamide treatments were comparable to those for placebo. Conclusion: The study provides evidence that confirms the efficacy of zonisamide 50 mg/d for reduction in "off" time in PD patients with wearing-off phenomena.

Original languageEnglish
Pages (from-to)1343-1350
Number of pages8
JournalMovement Disorders
Volume30
Issue number10
DOIs
Publication statusPublished - 2015 Sep 1

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zonisamide
Double-Blind Method
Parkinson Disease
Placebos
Dyskinesias

Keywords

  • Levodopa
  • Parkinson's disease
  • Randomized controlled trial
  • Wearing-off
  • Zonisamide

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Murata, M., Hasegawa, K., Kanazawa, I., Fukasaka, J., Kochi, K., Shimazu, R., ... Nagado, T. (2015). Zonisamide improves wearing-off in Parkinson's disease: A randomized, double-blind study. Movement Disorders, 30(10), 1343-1350. https://doi.org/10.1002/mds.26286

Zonisamide improves wearing-off in Parkinson's disease : A randomized, double-blind study. / Murata, Miho; Hasegawa, Kazuko; Kanazawa, Ichiro; Fukasaka, Junichi; Kochi, Kenji; Shimazu, Rieko; Kimura, Takashi; Yoshida, Kazuto; Kikuchi, Seiji; Baba, Masayuki; Chida, Keiji; Utsugizawa, Kimiaki; Abe, Takashi; Takeda, Atsushi; Kawanami, Toru; Kobayashi, Shunsuke; Yoshizawa, Kazuo; Tamaoka, Akira; Fujimoto, Kenichi; Okamoto, Koichi; Ryo, Masabuchi; Uematsu, Daisuke; Asahina, Masato; Hashida, Hideji; Uchiyama, Shinichiro; Suzuki, Norihiro; Utsumi, Hiroya; Orimo, Satoshi; Takanashi, Masashi; Mizusawa, Hidehiro; Kono, Yu; Okamoto, Tomoko; Yokochi, Fusako; Takubo, Hideki; Matsubayashi, Satoe; Yokoyama, Teruo; Akutsu, Tsugio; Mochizuki, Hideki; Yoshii, Fumihito; Shiraishi, Makoto; Ogino, Mieko; Yamada, Hitoshi; Kawashima, Noriko; Kawase, Yasuhiro; Yoneda, Makoto; Takiyama, Yoshihisa; Hashimoto, Takao; Miyajima, Hiroaki; Okuma, Yasuyuki; Mizoguchi, Koichi; Hattori, Tatsuya; Ishikawa, Mitsunori; Tatsuoka, Yoshihisa; Saiki, Hidemoto; Kato, Tomonobu; Fujimura, Harutoshi; Mitsui, Yoshiyuki; Nakamura, Yusaku; Kageyama, Yasufumi; Kajiyama, Koji; Toda, Kazuo; Nishimura, Yo; Suenaga, Toshihiko; Nakanishi, Ichiro; Nishida, Yoshihiko; Nagai, Masahiro; Yuhi, Tomoaki; Uozumi, Takenori; Sato, Akira; Matsuo, Hidenori; Tsuruta, Kazuhito; Matsumoto, Hideya; Nagado, Tatsui.

In: Movement Disorders, Vol. 30, No. 10, 01.09.2015, p. 1343-1350.

Research output: Contribution to journalArticle

Murata, M, Hasegawa, K, Kanazawa, I, Fukasaka, J, Kochi, K, Shimazu, R, Kimura, T, Yoshida, K, Kikuchi, S, Baba, M, Chida, K, Utsugizawa, K, Abe, T, Takeda, A, Kawanami, T, Kobayashi, S, Yoshizawa, K, Tamaoka, A, Fujimoto, K, Okamoto, K, Ryo, M, Uematsu, D, Asahina, M, Hashida, H, Uchiyama, S, Suzuki, N, Utsumi, H, Orimo, S, Takanashi, M, Mizusawa, H, Kono, Y, Okamoto, T, Yokochi, F, Takubo, H, Matsubayashi, S, Yokoyama, T, Akutsu, T, Mochizuki, H, Yoshii, F, Shiraishi, M, Ogino, M, Yamada, H, Kawashima, N, Kawase, Y, Yoneda, M, Takiyama, Y, Hashimoto, T, Miyajima, H, Okuma, Y, Mizoguchi, K, Hattori, T, Ishikawa, M, Tatsuoka, Y, Saiki, H, Kato, T, Fujimura, H, Mitsui, Y, Nakamura, Y, Kageyama, Y, Kajiyama, K, Toda, K, Nishimura, Y, Suenaga, T, Nakanishi, I, Nishida, Y, Nagai, M, Yuhi, T, Uozumi, T, Sato, A, Matsuo, H, Tsuruta, K, Matsumoto, H & Nagado, T 2015, 'Zonisamide improves wearing-off in Parkinson's disease: A randomized, double-blind study', Movement Disorders, vol. 30, no. 10, pp. 1343-1350. https://doi.org/10.1002/mds.26286
Murata M, Hasegawa K, Kanazawa I, Fukasaka J, Kochi K, Shimazu R et al. Zonisamide improves wearing-off in Parkinson's disease: A randomized, double-blind study. Movement Disorders. 2015 Sep 1;30(10):1343-1350. https://doi.org/10.1002/mds.26286
Murata, Miho ; Hasegawa, Kazuko ; Kanazawa, Ichiro ; Fukasaka, Junichi ; Kochi, Kenji ; Shimazu, Rieko ; Kimura, Takashi ; Yoshida, Kazuto ; Kikuchi, Seiji ; Baba, Masayuki ; Chida, Keiji ; Utsugizawa, Kimiaki ; Abe, Takashi ; Takeda, Atsushi ; Kawanami, Toru ; Kobayashi, Shunsuke ; Yoshizawa, Kazuo ; Tamaoka, Akira ; Fujimoto, Kenichi ; Okamoto, Koichi ; Ryo, Masabuchi ; Uematsu, Daisuke ; Asahina, Masato ; Hashida, Hideji ; Uchiyama, Shinichiro ; Suzuki, Norihiro ; Utsumi, Hiroya ; Orimo, Satoshi ; Takanashi, Masashi ; Mizusawa, Hidehiro ; Kono, Yu ; Okamoto, Tomoko ; Yokochi, Fusako ; Takubo, Hideki ; Matsubayashi, Satoe ; Yokoyama, Teruo ; Akutsu, Tsugio ; Mochizuki, Hideki ; Yoshii, Fumihito ; Shiraishi, Makoto ; Ogino, Mieko ; Yamada, Hitoshi ; Kawashima, Noriko ; Kawase, Yasuhiro ; Yoneda, Makoto ; Takiyama, Yoshihisa ; Hashimoto, Takao ; Miyajima, Hiroaki ; Okuma, Yasuyuki ; Mizoguchi, Koichi ; Hattori, Tatsuya ; Ishikawa, Mitsunori ; Tatsuoka, Yoshihisa ; Saiki, Hidemoto ; Kato, Tomonobu ; Fujimura, Harutoshi ; Mitsui, Yoshiyuki ; Nakamura, Yusaku ; Kageyama, Yasufumi ; Kajiyama, Koji ; Toda, Kazuo ; Nishimura, Yo ; Suenaga, Toshihiko ; Nakanishi, Ichiro ; Nishida, Yoshihiko ; Nagai, Masahiro ; Yuhi, Tomoaki ; Uozumi, Takenori ; Sato, Akira ; Matsuo, Hidenori ; Tsuruta, Kazuhito ; Matsumoto, Hideya ; Nagado, Tatsui. / Zonisamide improves wearing-off in Parkinson's disease : A randomized, double-blind study. In: Movement Disorders. 2015 ; Vol. 30, No. 10. pp. 1343-1350.
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title = "Zonisamide improves wearing-off in Parkinson's disease: A randomized, double-blind study",
abstract = "Background: Previously, we reported 50 mg/d zonisamide improved wearing-off without increasing dyskinesia in patients with Parkinson's disease (PD). Methods: To determine the efficacy of zonisamide for treatment of {"}off{"} time in PD patients, we conducted a multicenter, randomized, double-blind, parallel-group, placebo-controlled study in Japan. Patients with PD and wearing-off received placebo for 4 weeks and then were treated for 12 weeks with zonisamide 25 or 50 mg/d or placebo, in addition to their previous therapy. The primary endpoint was the change from baseline in daily {"}off{"} time as determined by patients' diaries at the final assessment. Secondary endpoints included changes from baseline in the total scores of the Unified Parkinson's Disease Rating Scale Parts I, II, III, and IV, the dyskinesia duration, and PDQ-39 score. Results: Of 422 patients enrolled, 389 (131 for placebo, 130 for zonisamide 25 mg, and 128 for zonisamide 50 mg) were randomized, and 354 (120, 119, and 115, respectively) completed the study. The {"}off{"} time significantly reduced by 0.719±0.179 h for zonisamide, 50 mg compared with placebo (0.011±0.173 h, P=0.005). Although the incidence of somnolence was higher for zonisamide (3.1{\%} for zonisamide 25 mg, 6.3{\%} for zonisamide 50 mg) than for placebo (2.3{\%}), the incidences of the other adverse events, including dyskinesia or hallucination, for both zonisamide treatments were comparable to those for placebo. Conclusion: The study provides evidence that confirms the efficacy of zonisamide 50 mg/d for reduction in {"}off{"} time in PD patients with wearing-off phenomena.",
keywords = "Levodopa, Parkinson's disease, Randomized controlled trial, Wearing-off, Zonisamide",
author = "Miho Murata and Kazuko Hasegawa and Ichiro Kanazawa and Junichi Fukasaka and Kenji Kochi and Rieko Shimazu and Takashi Kimura and Kazuto Yoshida and Seiji Kikuchi and Masayuki Baba and Keiji Chida and Kimiaki Utsugizawa and Takashi Abe and Atsushi Takeda and Toru Kawanami and Shunsuke Kobayashi and Kazuo Yoshizawa and Akira Tamaoka and Kenichi Fujimoto and Koichi Okamoto and Masabuchi Ryo and Daisuke Uematsu and Masato Asahina and Hideji Hashida and Shinichiro Uchiyama and Norihiro Suzuki and Hiroya Utsumi and Satoshi Orimo and Masashi Takanashi and Hidehiro Mizusawa and Yu Kono and Tomoko Okamoto and Fusako Yokochi and Hideki Takubo and Satoe Matsubayashi and Teruo Yokoyama and Tsugio Akutsu and Hideki Mochizuki and Fumihito Yoshii and Makoto Shiraishi and Mieko Ogino and Hitoshi Yamada and Noriko Kawashima and Yasuhiro Kawase and Makoto Yoneda and Yoshihisa Takiyama and Takao Hashimoto and Hiroaki Miyajima and Yasuyuki Okuma and Koichi Mizoguchi and Tatsuya Hattori and Mitsunori Ishikawa and Yoshihisa Tatsuoka and Hidemoto Saiki and Tomonobu Kato and Harutoshi Fujimura and Yoshiyuki Mitsui and Yusaku Nakamura and Yasufumi Kageyama and Koji Kajiyama and Kazuo Toda and Yo Nishimura and Toshihiko Suenaga and Ichiro Nakanishi and Yoshihiko Nishida and Masahiro Nagai and Tomoaki Yuhi and Takenori Uozumi and Akira Sato and Hidenori Matsuo and Kazuhito Tsuruta and Hideya Matsumoto and Tatsui Nagado",
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TY - JOUR

T1 - Zonisamide improves wearing-off in Parkinson's disease

T2 - A randomized, double-blind study

AU - Murata, Miho

AU - Hasegawa, Kazuko

AU - Kanazawa, Ichiro

AU - Fukasaka, Junichi

AU - Kochi, Kenji

AU - Shimazu, Rieko

AU - Kimura, Takashi

AU - Yoshida, Kazuto

AU - Kikuchi, Seiji

AU - Baba, Masayuki

AU - Chida, Keiji

AU - Utsugizawa, Kimiaki

AU - Abe, Takashi

AU - Takeda, Atsushi

AU - Kawanami, Toru

AU - Kobayashi, Shunsuke

AU - Yoshizawa, Kazuo

AU - Tamaoka, Akira

AU - Fujimoto, Kenichi

AU - Okamoto, Koichi

AU - Ryo, Masabuchi

AU - Uematsu, Daisuke

AU - Asahina, Masato

AU - Hashida, Hideji

AU - Uchiyama, Shinichiro

AU - Suzuki, Norihiro

AU - Utsumi, Hiroya

AU - Orimo, Satoshi

AU - Takanashi, Masashi

AU - Mizusawa, Hidehiro

AU - Kono, Yu

AU - Okamoto, Tomoko

AU - Yokochi, Fusako

AU - Takubo, Hideki

AU - Matsubayashi, Satoe

AU - Yokoyama, Teruo

AU - Akutsu, Tsugio

AU - Mochizuki, Hideki

AU - Yoshii, Fumihito

AU - Shiraishi, Makoto

AU - Ogino, Mieko

AU - Yamada, Hitoshi

AU - Kawashima, Noriko

AU - Kawase, Yasuhiro

AU - Yoneda, Makoto

AU - Takiyama, Yoshihisa

AU - Hashimoto, Takao

AU - Miyajima, Hiroaki

AU - Okuma, Yasuyuki

AU - Mizoguchi, Koichi

AU - Hattori, Tatsuya

AU - Ishikawa, Mitsunori

AU - Tatsuoka, Yoshihisa

AU - Saiki, Hidemoto

AU - Kato, Tomonobu

AU - Fujimura, Harutoshi

AU - Mitsui, Yoshiyuki

AU - Nakamura, Yusaku

AU - Kageyama, Yasufumi

AU - Kajiyama, Koji

AU - Toda, Kazuo

AU - Nishimura, Yo

AU - Suenaga, Toshihiko

AU - Nakanishi, Ichiro

AU - Nishida, Yoshihiko

AU - Nagai, Masahiro

AU - Yuhi, Tomoaki

AU - Uozumi, Takenori

AU - Sato, Akira

AU - Matsuo, Hidenori

AU - Tsuruta, Kazuhito

AU - Matsumoto, Hideya

AU - Nagado, Tatsui

PY - 2015/9/1

Y1 - 2015/9/1

N2 - Background: Previously, we reported 50 mg/d zonisamide improved wearing-off without increasing dyskinesia in patients with Parkinson's disease (PD). Methods: To determine the efficacy of zonisamide for treatment of "off" time in PD patients, we conducted a multicenter, randomized, double-blind, parallel-group, placebo-controlled study in Japan. Patients with PD and wearing-off received placebo for 4 weeks and then were treated for 12 weeks with zonisamide 25 or 50 mg/d or placebo, in addition to their previous therapy. The primary endpoint was the change from baseline in daily "off" time as determined by patients' diaries at the final assessment. Secondary endpoints included changes from baseline in the total scores of the Unified Parkinson's Disease Rating Scale Parts I, II, III, and IV, the dyskinesia duration, and PDQ-39 score. Results: Of 422 patients enrolled, 389 (131 for placebo, 130 for zonisamide 25 mg, and 128 for zonisamide 50 mg) were randomized, and 354 (120, 119, and 115, respectively) completed the study. The "off" time significantly reduced by 0.719±0.179 h for zonisamide, 50 mg compared with placebo (0.011±0.173 h, P=0.005). Although the incidence of somnolence was higher for zonisamide (3.1% for zonisamide 25 mg, 6.3% for zonisamide 50 mg) than for placebo (2.3%), the incidences of the other adverse events, including dyskinesia or hallucination, for both zonisamide treatments were comparable to those for placebo. Conclusion: The study provides evidence that confirms the efficacy of zonisamide 50 mg/d for reduction in "off" time in PD patients with wearing-off phenomena.

AB - Background: Previously, we reported 50 mg/d zonisamide improved wearing-off without increasing dyskinesia in patients with Parkinson's disease (PD). Methods: To determine the efficacy of zonisamide for treatment of "off" time in PD patients, we conducted a multicenter, randomized, double-blind, parallel-group, placebo-controlled study in Japan. Patients with PD and wearing-off received placebo for 4 weeks and then were treated for 12 weeks with zonisamide 25 or 50 mg/d or placebo, in addition to their previous therapy. The primary endpoint was the change from baseline in daily "off" time as determined by patients' diaries at the final assessment. Secondary endpoints included changes from baseline in the total scores of the Unified Parkinson's Disease Rating Scale Parts I, II, III, and IV, the dyskinesia duration, and PDQ-39 score. Results: Of 422 patients enrolled, 389 (131 for placebo, 130 for zonisamide 25 mg, and 128 for zonisamide 50 mg) were randomized, and 354 (120, 119, and 115, respectively) completed the study. The "off" time significantly reduced by 0.719±0.179 h for zonisamide, 50 mg compared with placebo (0.011±0.173 h, P=0.005). Although the incidence of somnolence was higher for zonisamide (3.1% for zonisamide 25 mg, 6.3% for zonisamide 50 mg) than for placebo (2.3%), the incidences of the other adverse events, including dyskinesia or hallucination, for both zonisamide treatments were comparable to those for placebo. Conclusion: The study provides evidence that confirms the efficacy of zonisamide 50 mg/d for reduction in "off" time in PD patients with wearing-off phenomena.

KW - Levodopa

KW - Parkinson's disease

KW - Randomized controlled trial

KW - Wearing-off

KW - Zonisamide

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