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Open Access 16-01-2024 | Levodopa | ORIGINAL RESEARCH

Impact of Istradefylline on Levodopa Dose Escalation in Parkinson’s Disease: ISTRA ADJUST PD Study, a Multicenter, Open-Label, Randomized, Parallel-Group Controlled Study

Authors: Taku Hatano, Renpei Sengoku, Hiroshi Nagayama, Naotake Yanagisawa, Asako Yoritaka, Keisuke Suzuki, Noriko Nishikawa, Yohei Mukai, Kyoichi Nomura, Norihito Yoshida, Morinobu Seki, Miho Kawabe Matsukawa, Hiroo Terashi, Katsuo Kimura, Jun Tashiro, Shigeki Hirano, Hidetomo Murakami, Hideto Joki, Tsuyoshi Uchiyama, Hideki Shimura, Kotaro Ogaki, Jiro Fukae, Yoshio Tsuboi, Kazushi Takahashi, Toshimasa Yamamoto, Kenichi Kaida, Ryoko Ihara, Kazutomi Kanemaru, Osamu Kano

Published in: Neurology and Therapy | Issue 2/2024

Abstract

Introduction

A higher levodopa dose is a risk factor for motor complications in Parkinson’s disease (PD). Istradefylline (IST) is used as adjunctive treatment to levodopa in PD patients with off episodes, but its impact on levodopa dose titration remains unclear. The objective of this study was to investigate the effect of IST on levodopa dose escalation in PD patients with wearing-off.

Methods

This was a multicenter, open-label, randomized, parallel-group controlled study (ISTRA ADJUST PD) in which PD patients experiencing wearing-off (n = 114) who were receiving levodopa 300–400 mg/day were randomized to receive IST or no IST (control). Levodopa dose was escalated according to clinical severity. The primary endpoint was cumulative additional levodopa dose, and secondary endpoints were changes in symptom rating scales, motor activity determined by a wearable device, and safety outcomes.

Results

The cumulative additional levodopa dose throughout 37 weeks and dose increase over 36 weeks were significantly lower in the IST group than in the control group (both p < 0.0001). The Movement Disorder Society Unified Parkinson’s Disease Rating Scale Part I and device-evaluated motor activities improved significantly from baseline to 36 weeks in the IST group only (all p < 0.05). Other secondary endpoints were comparable between the groups. Adverse drug reactions (ADRs) occurred in 28.8% and 13.2% of patients in the IST and control groups, respectively, with no serious ADRs in either group.

Conclusion

IST treatment reduced levodopa dose escalation in PD patients, resulting in less cumulative levodopa use. Adjunctive IST may improve motor function more objectively than increased levodopa dose in patients with PD.

Trial Registration

Japan Registry of Clinical Trials: jRCTs031180248.

Available only for authorised users

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Title: Impact of Istradefylline on Levodopa Dose Escalation in Parkinson’s Disease: ISTRA ADJUST PD Study, a Multicenter, Open-Label, Randomized, Parallel-Group Controlled Study
Authors: Taku Hatano
Renpei Sengoku
Hiroshi Nagayama
Naotake Yanagisawa
Asako Yoritaka
Keisuke Suzuki
Noriko Nishikawa
Yohei Mukai
Kyoichi Nomura
Norihito Yoshida
Morinobu Seki
Miho Kawabe Matsukawa
Hiroo Terashi
Katsuo Kimura
Jun Tashiro
Shigeki Hirano
Hidetomo Murakami
Hideto Joki
Tsuyoshi Uchiyama
Hideki Shimura
Kotaro Ogaki
Jiro Fukae
Yoshio Tsuboi
Kazushi Takahashi
Toshimasa Yamamoto
Kenichi Kaida
Ryoko Ihara
Kazutomi Kanemaru
Osamu Kano
Publication date: 16-01-2024
Publisher: Springer Healthcare
Keywords: Levodopa
Parkinson's Disease
Published in: Neurology and Therapy / Issue 2/2024
Print ISSN: 2193-8253
Electronic ISSN: 2193-6536
DOI: https://doi.org/10.1007/s40120-023-00574-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Impact of Istradefylline on Levodopa Dose Escalation in Parkinson’s Disease: ISTRA ADJUST PD Study, a Multicenter, Open-Label, Randomized, Parallel-Group Controlled Study

Abstract

Introduction

Methods

Results

Conclusion

Trial Registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusion

Trial Registration

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