Objective:

To assess effects of adjunctive opicapone (OPC) 50 mg on catechol-O-methyltransferase (COMT) activity by participants’ baseline characteristics.

Background:

OPC is a once-daily COMT inhibitor approved as adjunctive treatment to carbidopa/levodopa (CD/LD) in patients with Parkinson’s disease (PD) experiencing “OFF”-episodes. In two Phase 3 trials, OPC reduced daily “OFF”-time in patients with PD and motor fluctuations. 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.

Design/Methods:

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) assessing the effect of OPC 50 mg on LD pharmacokinetics (PK). 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. Pooled data on S-COMT inhibition were 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 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 percent reduction in S-COMT activity was 79–85% for all subgroups in individual and pooled studies, although some subgroups had small numbers of participants. Variability in S-COMT activity was lower in all participants after OPC compared to baseline.

Conclusions:

Adding once-daily OPC 50 mg to CD/LD resulted in substantial S-COMT inhibition with reduced variability regardless of baseline characteristics. In all participants, COMT inhibition shown by OPC with CD/LD leads to more consistent daily LD exposure.