Abstract Details

Title Once-Daily Opicapone Increases ON-Time in Patients with Parkinson’s Disease: Results from Two Phase 3 Studies

Topic Movement Disorders

Presentation(s) S4 - Clinical Trials in Movement Disorders (1:22 PM-1:33 PM)

Poster/Presentation
Number 003

Background

Catechol-O-methyltransferase (COMT) inhibitors were developed to prolong the clinical actions of levodopa. Opicapone is a novel, highly-selective, peripheral COMT inhibitor under development in the U.S. as an adjunct to levodopa for PD with motor fluctuations. The efficacy of opicapone has been evaluated in two international Phase 3 studies (BIPARK-1 [NCT01568073], BIPARK-2 [NCT01227655]).

Objective To evaluate changes with once-daily opicapone in ON-time in Parkinson’s disease (PD).

Design/Methods Participants received double-blind (DB) treatment with opicapone (5mg [BIPARK-1 only], 25mg, 50mg), entacapone 200mg (BIPARK-1 only), or placebo for 14-15 weeks added to levodopa. Participants completing DB treatment were eligible to enroll in the 1-year open-label (OL) phase of each study. Efficacy analyses included mean changes from baseline in absolute ON-time without troublesome dyskinesia (defined as either no dyskinesia or non-troublesome dyskinesia). Results for the 50mg opicapone dose are presented, along with dyskinesia as a treatment-emergent adverse event (TEAE).

Results In BIPARK-1 (opicapone at 5mg=119, 25mg=116, 50mg=115; entacapone=120; placebo=120), a significant increase from baseline to Week 14/15 in absolute ON-time without troublesome dyskinesia was found for opicapone 50mg versus placebo (least-squares mean change [±standard error], hours): 50mg, 1.9±0.2; placebo, 0.9±0.2; P=0.002. Similar results arose from BIPARK-2 (25mg=125, 50mg=147, placebo=135): 50mg, 1.7±0.3; placebo, 0.9±0.3; P=0.025. Improvements in ON-time without troublesome dyskinesia were sustained in long-term extension studies, with mean changes from DB baseline to OL endpoint (±standard deviation) in all opicapone-treated participants of 2.0±2.6 hours for BIPARK-1 (N=494) and 1.8±3.2 hours for BIPARK-2 (N=339). In the pooled DB safety population (N=631), a TEAE of dyskinesia was reported in 17.4% of all opicapone-treated (versus 6.2% for placebo). Few subjects had dyskinesia TEAE leading to discontinuation (opicapone, 1.9%; placebo, 0.4%) or serious dyskinesia (opicapone, 0.3%, placebo, 0%).

Conclusions Once-daily opicapone increased ON-time without troublesome dyskinesia in PD patients with motor fluctuations.

Authors/Disclosures
Peter A. LeWitt, MD (Henry Ford Hospital - Franklin Pointe) PRESENTER	Dr. LeWitt has received personal compensation for serving as an employee of Supernus. Dr. LeWitt has received personal compensation for serving as an employee of Amneal. Dr. LeWitt has received personal compensation for serving as an employee of Hoffmann-La Roche - Genentech. Dr. LeWitt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Tanabe-NeuroDerm Neuropharma. Dr. LeWitt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bukwang Pharmaceuticals. Dr. LeWitt has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neurocrine. Dr. LeWitt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Supernus. The institution of Dr. LeWitt has received research support from Michael J Fox Foundation.
Daniel O. Claassen, MD, FAAN (Vanderbilt University Medical Center)	Dr. Claassen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Spark . The institution of Dr. Claassen has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Alterity. Dr. Claassen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for University of Michigan. Dr. Claassen has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for HD Insights. The institution of Dr. Claassen has received research support from NIH. The institution of Dr. Claassen has received research support from CHDI. The institution of Dr. Claassen has received research support from HDSA. The institution of Dr. Claassen has received research support from Department of Defense. The institution of Dr. Claassen has received research support from CHDI. The institution of Dr. Claassen has received research support from Genentech/ Roche.
Kurt Olson	Kurt Olson has received personal compensation for serving as an employee of Neurocrine Biosciences Inc. Kurt Olson has stock in Neurocrine Biosciences Inc.
Khodayar Farahmand	Mr. Farahmand has received personal compensation for serving as an employee of Neurocrine Biosciences, Inc.
Scott Siegert	Mr. Siegert has received personal compensation for serving as an employee of Neurocrine Biosciences. Mr. Siegert has stock in Neurocrine Biosciences.
	No disclosure on file
Francisco Rocha	Francisco Rocha has received personal compensation for serving as an employee of BIAL - Portela.
Patricio Soares-da-Silva	Patricio Soares-da-Silva has received personal compensation for serving as an employee of Bial - Portela & Cª S.A.. Patricio Soares-da-Silva has received personal compensation in the range of $100,000-$499,999 for serving as an officer or member of the Board of Directors for Bial - Portela & Cª S.A..
Grace L. Liang, MD	Dr. Liang has received personal compensation for serving as an employee of Neurocrine Biosciences. Dr. Liang has stock in Neurocrine Biosciences.

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