P32_NONCE - Once-Daily Opicapone Improves OFF-Time in Patients with Parkinson’s Disease and Motor Fluctuations: Pooled Subgroup Analysis of Two Randomized, Double-Blind, Placebo-Controlled Studies

Purpose: To evaluate the effects of once-daily opicapone on OFF-time in subgroups of patients with Parkinson’s disease (PD) and motor fluctuations.

Rationale: Opicapone is a novel and highly selective catechol-O-methyltransferase (COMT) inhibitor under development in the US as an adjunct to carbidopa/levodopa for PD fluctuations. In two pivotal Phase 3 studies (BIPARK-1 [NCT01568073], BIPARK-2 [NCT01227655]), opicapone 50mg significantly reduced OFF-time relative to placebo (primary endpoint). Additional information regarding the effects of opicapone in various patient subpopulations are warranted.

Methods: Participants were randomized to 14-15 weeks of treatment with opicapone (5mg [BIPARK-1 only], 25mg, 50mg), entacapone (BIPARK-1 only), or placebo, added to their levodopa plus dopa decarboxylase inhibitor (DDCI) regimen. Least squares (LS) mean changes from baseline to Week 14/15 in absolute OFF-time were analyzed in the pooled population and in subgroups defined by the following baseline factors: age, gender, race, modified Hoehn and Yahr (H&Y) stage during ON, DDCI treatment (carbidopa or benserazide), and concurrent use of other PD medications (dopamine agonists [DA] or monoamine oxidase-B inhibitors [MAOBI]). Participants receiving both levodopa/DDCI formulations (carbidopa and benserazide) were excluded from subgroup analyses due to the small number. All analyses were conducted using a mixed model for repeated measures. Results for opicapone 50mg (targeted clinical dose) are presented.

Results: In the overall pooled population (placebo n=255; 50mg n=262), opicapone 50mg significantly reduced (improved) OFF-time versus placebo at Week 14/15 (LS mean change ±standard error [SE], hours): 50mg, -2.22±0.17; placebo, -1.28±0.17; P