Opicapone for the treatment of early wearing-off in levodopa-treated Parkinson's disease: pooled analysis of patient level data from two randomized open-label studies.

Background: The wearing-off phenomenon is a key driver of medication change for patients with Parkinson's disease (PD) treated with levodopa. Common first-line options include increasing the levodopa dose or adding a catechol-O-methyltransferase (COMT) inhibitor, but there are no trials comparing the efficacy of these approaches. We evaluated the effectiveness of adjunct opicapone versus an additional 100 mg levodopa dose in PD patients with early wearing-off using pooled data from 2 randomized studies.

Methods: The ADOPTION study program included two similarly designed 4-week, open-label studies conducted in South Korea (NCT04821687) and Europe (NCT04990284). Patients with PD, treated with 3-4 daily doses of levodopa therapy and with signs of early wearing-off were randomized (1:1) to adjunct opicapone 50 mg or an additional dose of levodopa 100 mg. Patient-level data from the two studies were pooled.

Results: The adjusted mean [SE] change from baseline to week 4 in absolute OFF time (key endpoint) was - 62.8 min [8.8] in the opicapone group and - 33.8 min [9.0] in the levodopa 100 mg group, the difference significantly favoring opicapone (- 29.0 [- 53.8, - 4.2] min, p = 0.02). Significant differences in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III subscore (- 4.1 with opicapone vs - 2.5 with levodopa 100 mg), also favored opicapone (- 1.7 [- 3.3, - 0.04], p < 0.05). Dyskinesia was the most frequently reported adverse event (opicapone 7.2% vs. levodopa 100 mg 4.2%).

Conclusions: In these short-term trials, introducing adjunct opicapone was more effective at reducing OFF time than adding another 100 mg levodopa dose in PD patients with early signs of wearing-off.