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Clinical Trial
. 2025 Jan;32(1):e16420.
doi: 10.1111/ene.16420.

Opicapone as adjunct to levodopa in treated Parkinson's disease without motor complications: A randomized clinical trial

Joaquim J Ferreira  1   2 , Olivier Rascol  3 , Fabrizio Stocchi  4 , Angelo Antonini  5 , Joana Moreira  6 , Guillermo Castilla-Fernández  7 , José-Francisco Rocha  6 , Joerg Holenz  6 , Werner Poewe  8 ; Epsilon Study investigators
Collaborators, Affiliations
Clinical Trial

Opicapone as adjunct to levodopa in treated Parkinson's disease without motor complications: A randomized clinical trial

Joaquim J Ferreira et al. Eur J Neurol. 2025 Jan.

Abstract

Background: Catechol-O-methyl transferase (COMT) inhibitors are routinely used to manage motor fluctuations in Parkinson's disease (PD). We assessed the effect of opicapone on motor symptom severity in levodopa-treated patients without motor complications.

Methods: This was a randomized, double-blind, 24-week, placebo-controlled study of opicapone 50 mg as adjunct to levodopa (NCT04978597). Levodopa-treated patients without motor complications were randomized to 24 weeks of double-blind treatment with adjunct opicapone 50 mg or matching placebo. The primary efficacy endpoint was the mean change from baseline to week 24 in Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) total score.

Results: A total of 355 patients were randomized (opicapone 50 mg n = 177, placebo n = 178) and 322 (91%) completed the double-blind period. The adjusted mean [95% CI] change from baseline to week 24 in MDS-UPDRS-III subscore was -6.5 [-7.9, -5.2] in the opicapone group versus -4.3 [-5.7, 3.0] in the placebo group resulting in a significant difference of -2.2 [-3.9, -0.5] favoring opicapone (p = 0.010). There was no difference in the incidence of patients who developed motor complications (5.5% with opicapone vs. 9.8% with placebo) and the incidence of adverse events considered related to study medication was similar between groups (opicapone 10.2% vs. placebo 13.5%).

Conclusions: Treatment with once-daily adjunct opicapone was well tolerated, improved motor severity, and did not induce the development of motor complications. These results support the clinical usefulness of opicapone in the management of PD patients without motor complications.

Keywords: COMT; Parkinson's disease; clinical trial; levodopa; opicapone.

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Conflict of interest statement

Joaquim J. Ferreira, Olivier Rascol, Fabrizio Stocchi, Angelo Antonini, and Werner Poewe were all investigators in the Epsilon study and report fees for consultancy from BIAL. Joana Moreira, Guillermo Castilla‐Fernández, José‐Francisco Rocha, and Joerg Holenz are employed by BIAL. In addition, Joaquim J. Ferreira has provided consultancy for AbbVie, BIAL, Biogen, Lundbeck, and Sunovion; has received grants from Angelini, Novartis, Medtronic, AbbVie, Zambon, BIAL, Biogen, and Grunenthal; and has received speaker fees for BIAL, Ono, SK Chemical, and Infucure. Olivier Rascol has participated in advisory boards and/or provided consultancy for AbbVie, Adamas, Acorda, Addex, AlzProtect, ApoPharma, AstraZeneca, Axovant, BIAL, Biogen, Britannia, Buckwang, CereSpir, Clevexel, Denali, INC Research, IPMDS, Lundbeck, Lupin, Merck, MundiPharma, NeurATRIS, NeuroDerm, Novartis, ONO Pharma, Osmotica, Parexel, Pfizer, Prexton Therapeutics, Quintiles, Roche, Sanofi, Servier, Sunovion, Theranexus, Takeda, Teva, UCB, Vectura, Watermark Research, XenoPort, XO, and Zambon; and has received grants from Agence Nationale de la Recherche (ANR), CHU de Toulouse, France‐Parkinson, INSERM‐DHOS Recherche Clinique Translationnelle, The Michael J. Fox Foundation, Programme Hospitalier de Recherche Clinique, European Commission (FP7, H2020), and Cure Parkinson's. Fabrizio Stocchi reports honoraria and consulting fees from BIAL, Sunovion, AbbVie, Luosofarmaco, Kjowa, Synagile, Lundbeck, TEVA, UCB, Zambon, Blue Rock, NeuroDerm, Contera, Zambon, Biogen, Ever, and Britannia; speaker fees from BIAL, Sunovion, AbbVie, Luosofarmaco, Kyowa, Synagile, Lundbeck, TEVA, UCB, and Zambon; and travel support from BIAL, Zambon, Synagile, and AbbVie. Angelo Antonini has received compensation for consultancy and speaker‐related activities from UCB, Boehringer Ingelheim, Britannia, AbbVie, Zambon, BIAL, NeuroDerm, Theravance Biopharma, Roche; he receives research support from Chiesi Pharmaceuticals, Lundbeck, Horizon 2020 ‐ Grant 825,785, Horizon2020 Grant 101,016,902, Ministry of Education University and Research (MIUR) Grant ARS01_01081, Cariparo Foundation. He serves as consultant for Boehringer Ingelheim for legal cases on pathological gambling; owns Patent WO2015110261‐A1; and owns shares in PD Neurotechnology Limited. Guillermo Castilla‐Fernández, José‐Francisco Rocha, and Joerg Holenz are employed by BIAL. Werner Poewe has received lecture fees and honoraria for consultancy in relation to clinical drug development programs from AbbVie, AC Immune, Alterity, BIAL, Boehringer, Britannia, Lilly, Eisai, Lundbeck, Roche, Takeda, Britannia, Eisai, Roche, Stada, and Zambon; grant support from The Michael J. Fox Foundation and the EU FP7 & Horizon 2020 programs; and safety monitoring board membership for UCB. He has leadership roles in the Movement Disorder Society, Austrian Society of Neurology, and Austrian PD Society.

Figures

FIGURE 1
FIGURE 1
Patient disposition. FAS, full analysis set. *Sponsor decision due to the conflict in Ukraine.
FIGURE 2
FIGURE 2
Change from baseline in Movement Disorder Society sponsored revision of the Unified Parkinson's Disease Rating Scale Part III (MDS‐UPDRS‐III) scores at double‐blind (DB) study endpoint. LS, least squares; SE, standard error.
See this image and copyright information in PMC

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