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Background: Increasing levodopa (L‐dopa)/dopa decarboxylase inhibitor (DDCI) daily dose or adding a catechol‐O‐methyltransferase (COMT) inhibitor to levodopa/DDCI therapy are strategies used to manage wearing‐off symptoms in Parkinson's disease (PD) patients. Objectives: To evaluate the COMT inhibitor opicapone versus an additional dose of levodopa to treat early wearing‐off in PD patients. Methods: ADOPTION was a randomized, parallel‐group, open‐label, Phase 4 study conducted in Korea. At baseline, eligible patients were randomized (1:1) to opicapone 50 mg (n = 87) or L‐dopa 100 mg (n = 81) (added to current L‐dopa/DDCI therapy) for 4 weeks. The main efficacy endpoint was change from baseline to end of study in absolute off time. Other endpoints included changes in on time, in Movement Disorder Society‐Unified Parkinson's Disease Rating Scale and 8‐item PD Questionnaire scores, and the Clinical and Patient Global Impression of Improvement/Change. Results: The adjusted mean in absolute off time was significantly greater for opicapone 50 mg than for L‐dopa 100 mg (−62.1 vs. −16.7 minutes; P = 0.0015). Opicapone‐treated patients also reported a greater reduction in the percentage of off time (P = 0.0015), a greater increase in absolute on time (P = 0.0338) and a greater increase in the percentage of on time (P = 0.0015). There were no significant differences in other secondary endpoints. The L‐dopa equivalent daily dose was significantly higher in the opicapone group (750.9 vs. 690.0 mg; P = 0.0247), when a 0.5 conversion factor is applied. Conclusions: Opicapone 50 mg was more effective than an additional 100 mg L‐dopa dose at decreasing off time in patients with PD and early wearing‐off. [ABSTRACT FROM AUTHOR]

This multicentre, prospective, single-arm study evaluated safinamide as add-on therapy to levodopa in Korean patients with Parkinson’s disease (PD) with motor fluctuations with ≥ 1.5 h of “off” time daily, who took levodopa ≥ 3 times/day (n = 199). Baseline levodopa and dopamine agonist doses were maintained without escalation during the 18-week treatment period. Participants received safinamide 50 mg/day for 2 weeks and 100 mg/day thereafter. PD diaries and questionnaires (Parkinson’s Disease Questionnaire, PDQ-39; Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale, MDS–UPDRS part 3 and part 4; King’s Parkinson’s Disease Pain Scale, KPPS; Mini-Mental State Examination, MMSE) were assessed at baseline and at week 18. Treatment-emergent adverse events (TEAEs) were recorded. Mean disease duration was 6.6 years, and mean levodopa equivalent daily dose was 721.1 mg/day. At week 18, significant improvements from baseline were seen for the co-primary endpoints, mean daily “off” time (− 1.3 ± 2.4 h, p < 0.001) and quality of life (QoL) based on PDQ-39 summary index (− 2.7 ± 10.3, p < 0.001), Moreover, significant improvements were seen in motor symptoms and motor complications (MDS-UPDRS part 3 and 4), daily “on” time without dyskinesia (all p < 0.001) and pain (KPPS; p = 0.013). TEAEs occurred in 40.2% of patients, with most being mild in severity. In conclusion, safinamide at a dosage of 100 mg/day significantly improved motor symptoms, QoL, and pain, and demonstrated a favourable safety profile without levodopa dosage escalation during the 18-week treatment period in Korean patients with PD.Trial registration number and date: NCT05312632, First Posted: April 5, 2022 [ABSTRACT FROM AUTHOR]