The investigators noted that the data on tolerability and efficacy support that treatment with opicapone among older adults with PD requires no age-related dose adjustments.
The results of a poster presentation at the 2022 Advanced Therapeutics in Movement and Related Disorders (ATMRD) Congress in Washington, DC, June 17-19, suggest that add-on, once-daily treatment with opicapone 50 mg (Ongentys; Neurocrine Biosceicnes) as adjunctive treatment to levodopa/carbidopa can be safe and effective in patient with Parkinson disease (PD) who experience OFF episodes.1
The data show that treatment-emergent adverse events (AEs) were slightly more common in older patients—both on treatment and placebo—though the 50-mg dose of opicapone, the recommended dose for those without hepatic impairment, displayed tolerability among these individuals, which the investigators wrote “support[s] that opicapone requires no dose adjustments for age.”
The investigators, including Jacqueline “Jacci” Bainbridge, PharmD, FCCP, professor of clinical pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, included participants from the BIPARK-1 study (NCT015668073), who were randomly assigned 1:1:1:1 to either 5-mg, 25-mg, or 50-mg opicapone; 200-mg entacapone; or placebo; as well as the BIPARK-2 study (NCT91227655), who were randomly assigned 1:1:1 to either 25-mg or 50-mg opicapone or placebo. The pooled safety population included 522 patients on either 50-mg opicapone (n = 265) or placebo (n = 257).
“In the pivotal phase 3 studies BIPARK-1 and BIPARK-2, levodopa-treated adults with PD and motor fluctuations had a significantly greater reduction in daily OFF time with adjunctive opicapone 50 mg versus placebo,” Bainbridge et al wrote. “Post hoc pooled analyses indicated treatment effects with opicapone 50 mg in patients [65 years and older] were comparable to the overall study population.”
For those ages 65 years and older, the change from baseline to week 14/15in absolute OFF time was –2.25 hours for those on opicapone (n = 139) compared with –1.12 hours for the placebo group (n = 112), which was significant (P <.001). In the full analysis set, the results were similar, as suggested by Bainbridge et al (opicapone: n = 262, –2.22 hours; placebo: n = 255, –1.28 hours; P <.001).
The change in absolute ON time from baseline to week 14/15 was also similar, with the older subgroup experiencing a gain of 2.0 hours compared with 0.85 hours for those on placebo (P <.001). In the full analysis set, the results were gains of 1.91 hours and 1.03 hours for the opicapone and placebo groups, respectively (P <.001).
As for safety, Bainbridge and colleagues noted that “the most common [treatment-emergent AE] was dyskinesia in both the overall safety population and in older patients, and few patients had serious dyskinesia in either the overall safety population (placebo, 0%; opicapone 50 mg, 0.4%) or in older patients (placebo, 0%; opicapone 50 mg,0.7%).” Additionally, there were very few discontinuations because of dyskinesia among opicapone-treated patients in either the full analysis set or in the older adult subgroup—3.0% and 2.2%, respectively—compared with the matching placebo groups—0.4% and 0%, respectively.
Other treatment-emergent AEs reported among those groups included constipation (placebo: 1.8% [n = 2]; opicapone 50 mg: 8.6% [n = 12]), insomnia (placebo: 2.7% [n = 3]; opicapone 50 mg: 3.6% [n = 5]), and dry mouth (placebo: 2.7% [n = 3]; opicapone 50 mg: 3.6% [n = 5]).
Notably, Bainbridge et al wrote, “opicapone 25 mg did not result in fewer [treatment-emergent AEs] than opicapone 50 mg in either the overall safety population (25 mg: 62.3%; 50 mg: 64.2%) or in older patients (25 mg: 68.2%; 50 mg: 66.9%).”