Category: Parkinson’s Disease: Clinical Trials
Objective: To compare the safety and tolerability of once-daily opicapone (OPC) 50mg as add-on to stable levodopa/dopa decarboxylase inhibitor (L-DOPA/DDCI) therapy in patients from early to late-stage Parkinson’s disease (PD).
Background: Post-hoc analysis of the BIPARK-I and II (BIPARKs) pivotal trials showed that OPC had a more favorable safety profile when used earlier in PD patients with motor fluctuations [1].
The EPSILON trial was implemented to further assess OPC as add-on to stable L‑DOPA/DDCI in early-stage PD patients without motor complications.
Method: BIPARKs results have been published previously [2,3]. These were phase 3, multicenter, randomized, double-blind (DB), placebo (PL)-controlled trials of OPC as an adjunct to L-DOPA/DDCI in PD patients with end-of-dose motor fluctuations. They had similar designs, eligibility criteria and methods [4].
EPSILON was a phase 3, multicenter, DB, PL-controlled, parallel-group study in PD patients without motor fluctuations randomly assigned 1:1 to 1 of 2 treatment arms (OPC or PL) for 24 weeks [5].
Safety and tolerability assessments were collected as secondary endpoints in the 3 studies. This analysis compares treatment-emergent adverse events (TEAEs) between BIPARKs and EPSILON safety data.
Results: The DB safety analysis set included 522 (265 OPC vs 257 PL) PD patients in BIPARKs and 355 (177 OPC vs 178 PL) in EPSILON.
The incidence of any TEAE was greater in BIPARKs (OPC 64.2% vs PL 57.2%) vs EPSILON (OPC 47.5% vs PL 47.2%).
Most frequently reported TEAEs belonged to SOC Nervous System Disorders, in the OPC arm in BIPARKs (34.3% vs PL 23.7%), and in the PL arm in EPSILON (16.6% vs OPC 13.6%). In line, dyskinesia was lower in OPC arm in EPSILON (1.1% vs PL 3.9%) but higher in OPC arm in BIPARKs (20.4% vs PL 6.2%).
Related TEAEs and discontinuation due to TEAEs, were less frequently reported with OPC in EPSILON (10.2% vs PL 13.5% and 1.1% vs PL 3.9%, respectively), contrary to BIPARKs (42,6% vs PL 29.2% and 8.7% vs PL 7.0%, respectively).
Serious related TEAEs were reported in 2 OPC patients in BIPARKs (6 in PL) and no case in OPC arm in EPSILON (1 in PL). No fatal case related to OPC was reported in the 3 studies.
Conclusion: The safety/tolerability comparison between BIPARKs and EPSILON studies confirms the favorable tolerability for OPC in PD patients, highlighting a similar profile to PL in PD patients without motor complications.
References: 1. Rocha JF, Ebersbach G, Lees A, Tolosa E, Ferreira JJ, Poewe W, Rascol O, Stocchi F, Antonini A, Magalhães D, Gama H, Soares-da-Silva P. The safety/tolerability of opicapone when used early in Parkinson’s disease patients with levodopa-induced motor fluctuations: A post-hoc analysis of BIPARK-I and II. Front Neurol. 2022 Aug 23;13:994114. Doi: 10.3389/fneur.2022.994114. PMID: 36081875; PMCID: PMC9446144.
2. Ferreira JJ, Lees A, Rocha JF, Poewe W, Rascol O, Soares-da-Silva P, et al. Opicapone as an adjunct to levodopa in patients with Parkinson’s disease and end-of-dose motor fluctuations: a randomised, double-blind, controlled trial. Lancet Neurol. (2016) 15:154–65. Doi: 10.1016/S1474-4422(15)00336-1
3. Lees AJ, Ferreira J, Rascol O, Poewe W, Rocha JF, McCrory M, et al. Opicapone as adjunct to levodopa therapy in patients with Parkinson disease and motor fluctuations: a randomized clinical trial. JAMA Neurol. (2017) 74:197–206. doi: 10.1001/jamaneurol.2016.4703
4. Nadjar A, Gerfen CR, Bezard E. Priming for l-dopa-induced dyskinesia in Parkinson’s disease: a feature inherent to the treatment or the disease? Prog Neurobiol. (2009) 87:1–9. doi: 10.1016/j.pneurobio.2008.09.013
5. Ferreira JJ, Rascol O, Stocchi F, Antonini A, Moreira J, Castilla-Fernández G, Rocha JF, Holenz J, Poewe W. Opicapone as adjunctive to levodopa-treated Parkinson’s disease patients without motor complications: Preliminary data from the EPSILON Study. International Congress of Parkinson’s Disease and Movement Disorders (MDS) 2023, Copenhagen, Denmark. August 27–31-Late Breaking Abstracts.
To cite this abstract in AMA style:
G. Cordeiro, I. Peixoto, H. Gama, L. Magalhães, J. Moreira, J-F. Rocha, J. Holenz. Safety and tolerability of opicapone in Parkinson’s Disease: from early-stage (EPSILON study) to late-stage (BIPARK studies) [abstract]. Mov Disord. 2024; 39 (suppl 1). https://www.mdsabstracts.org/abstract/safety-and-tolerability-of-opicapone-in-parkinsons-disease-from-early-stage-epsilon-study-to-late-stage-bipark-studies/. Accessed May 19, 2025.« Back to 2024 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/safety-and-tolerability-of-opicapone-in-parkinsons-disease-from-early-stage-epsilon-study-to-late-stage-bipark-studies/