Objective: To assess the effects of opicapone (OPC) 50 mg adjunct to carbidopa/levodopa (CD/LD) on catechol-O-methyltransferase (COMT) activity by participants’ baseline characteristics using pooled data from two Phase 1 studies.

Background: OPC is a once-daily COMT inhibitor approved in the US as an adjunctive treatment to CD/LD in patients with Parkinson’s disease (PD) experiencing “OFF” episodes. OPC was shown to reduce daily “OFF”-time in patients with PD and motor fluctuations in two pivotal Phase 3 trials. Two previous Phase 1 trials also showed that adding OPC 50 mg to CD/LD in healthy individuals and patients with PD decreased variability in plasma levodopa (LD) levels and COMT activity. However, the effects of participants’ baseline characteristics on COMT inhibition remain unknown.

Method: This post-hoc analysis included data from 2 open-label Phase 1 studies (Study 1: 16 patients with PD receiving immediate-release CD/LD; Study 2: 18 healthy participants receiving extended-release CD/LD) designed to assess the effect of OPC 50 mg on LD pharmacokinetics (PK) (Table 1). Blood samples to assess LD PK and soluble-COMT (S-COMT) activity were collected before and after 14–15 days of once-daily OPC 50 mg administration. Data on S-COMT inhibition were pooled and analyzed by participants’ baseline characteristics: disease state (PD vs healthy), sex (male vs female), ethnicity (Hispanic/Latino vs non-Hispanic/Latino), body mass index (<25 vs ≥25), and baseline S-COMT activity.

Results: OPC added to CD/LD decreased mean (95% CI) S-COMT activity by ≥80% in both patients with PD and healthy participants (Study 1: 83.0% [80.5–85.4%], Study 2: 80.1% [78.5–81.8%], Pooled: 81.4% [80.0–82.9%]). Mean % reduction in S-COMT activity was 79–85% for all subgroups in both individual and pooled studies, although some subgroups had small participant numbers. Variability in S-COMT activity was lower after OPC compared to baseline.

Conclusion: Adding once-daily OPC 50 mg to CD/LD resulted in substantial S-COMT inhibition with reduced variability regardless of disease state, age, gender, ethnicity, or other factors. In all participants regardless of demographics, COMT inhibition shown by OPC with CD/LD leads to more consistent daily LD exposure, which continues to be a challenge and goal in treating PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/effects-of-once-daily-opicapone-50-mg-on-comt-activity-a-pooled-post-hoc-analysis-of-two-phase-1-studies/