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

• Published in: Neurology and therapy Vol. 13; no. 2; pp. 323 - 338
• Main Authors: Hatano, Taku, Sengoku, Renpei, Nagayama, Hiroshi, Yanagisawa, Naotake, Yoritaka, Asako, Suzuki, Keisuke, Nishikawa, Noriko, Mukai, Yohei, Nomura, Kyoichi, Yoshida, Norihito, Seki, Morinobu, Matsukawa, Miho Kawabe, Terashi, Hiroo, Kimura, Katsuo, Tashiro, Jun, Hirano, Shigeki, Murakami, Hidetomo, Joki, Hideto, Uchiyama, Tsuyoshi, Shimura, Hideki, Ogaki, Kotaro, Fukae, Jiro, Tsuboi, Yoshio, Takahashi, Kazushi, Yamamoto, Toshimasa, Kaida, Kenichi, Ihara, Ryoko, Kanemaru, Kazutomi, Kano, Osamu
• Format: Journal Article
• Language: English
• Published: Cheshire Springer Healthcare 01.04.2024; Adis, Springer Healthcare
• Subjects: Adenosine A2A receptor antagonist; Internal Medicine; Istradefylline; jRCTs; jRCTs031180248; Levodopa; Levodopa dose; Medicine; Medicine & Public Health; Neurology; Original Research; Parkinson’s disease; Levodopa dose; Istradefylline; Levodopa; receptor antagonist; Parkinson’s disease; Adenosine A; Adenosine A2A receptor antagonist
• ISSN: 2193-8253; 2193-6536
• DOI: 10.1007/s40120-023-00574-6

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.