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P31_NONCE - Safety and Tolerability of Once-Daily Opicapone in Patients with Parkinson’s Disease and Motor Fluctuations: Pooled Analysis of Two Randomized, Double-Blind, Placebo-Controlled Studies

Purpose: To evaluate the safety and tolerability of once-daily opicapone in adults with Parkinson’s disease (PD) and motor fluctuations.

Rationale: Catechol-O-methyltransferase (COMT) inhibitors have been approved in the United States (US) as adjunctive therapies to levodopa, but previously available medications are limited by tolerability and safety issues. Opicapone is a novel and highly-selective COMT inhibitor under development in the US as an adjunct to carbidopa/levodopa for PD fluctuations.

Methods: Data were pooled from two pivotal phase 3 studies (BIPARK-1 [NCT01568073], BIPARK-2 [NCT01227655]) in which participants received once-daily opicapone (5mg [BIPARK-1 only], 25mg, 50mg), entacapone (BIPARK-1 only), or placebo for 14-15 weeks in addition to their levodopa regimen. Entacapone was not included in the pooled analysis. Assessments included treatment-emergent adverse events (TEAEs), laboratory tests, vital signs, and electrocardiograms (ECGs). The Modified Minnesota Impulse Disorders Interview (mMIDI) and TEAEs were used to assess compulsive behaviors.

Results: In this pooled analysis (N=888: placebo=257, opicapone 5mg=122, 25mg=244, 50mg=265]), the TEAE incidence was as follows: any TEAE (placebo=57.2%, 5mg=51.6%, 25mg=62.3%, 50mg=64.2%); serious TEAEs (placebo=4.3%, 5mg=3.3%, 25mg=2.0%, 50mg=4.9%); and TEAEs leading to discontinuation (placebo=7.4%, 5mg=5.7%, 25mg=5.7%, 50mg=9.1%). Dyskinesia was the most common TEAE in all treatment groups, but few participants had dyskinesia leading to discontinuation (placebo=0.4%, 5mg=1.6%, 25mg=0.8%, 50mg=3.0%) or serious dyskinesia (placebo=0%, 5mg=0%, 25mg=0.4%, 50mg=0.4%). No Hy’s law cases or severe/serious hepatobiliary TEAEs were reported in opicapone-treated participants except for 1 case of acute cholecystitis (50mg); two participants (25mg) reported urine discoloration. There were no clinically relevant differences between opicapone and placebo in laboratory parameters, vital signs, or ECGs. The incidence of mMIDI compulsive behaviors during opicapone treatment (combined doses) was comparable to baseline for buying disorder (baseline=9.8%; post-baseline=9.3%), pathological gambling (baseline=2.0%; post-baseline=0.9%), and compulsive sexual behavior (baseline=1.5%; post-baseline=2.2%). Few participants experienced impulse control disorders as a TEAE (placebo=0%, 5mg=0.8%, 25mg=0.4%, 50mg =1.1%).

Applicability to APN practice: Opicapone, which is under development in the US as a once-daily adjunct to carbidopa/levodopa, was generally safe and well-tolerated in clinical trials. TEAEs reported with other COMT inhibitors, such as hepatic injury and serious/severe diarrhea, were not observed and the incidence of compulsive behaviors was low.