Abstract Details

Title Efficacy and Safety of SEP-363856, a Non–D2-Receptor Binding Drug With Antipsychotic Activity, in Patients With Parkinson’s Disease Psychosis

Topic Movement Disorders

Presentation(s) S3 - Movement Disorders 1 (2:32 PM-2:40 PM)

Poster/Presentation
Number 005

Background PDP is a frequent, debilitating symptom of PD; current treatments may worsen motor function. In a pivotal study, SEP-363856—a trace amine-associated receptor-1 agonist with 5-hydroxytryptamine 1A agonist activity—was effective and generally well-tolerated for acute psychosis in schizophrenia.

Objective To evaluate the efficacy and safety of SEP-363856 for Parkinson’s disease psychosis (PDP) treatment.

Design/Methods In this controlled study (NCT02969369), patients with PDP requiring treatment were randomized (2:1) to flexibly dosed SEP-363856 (25, 50, or 75 mg/day) or placebo. Primary endpoint was Scale for Assessment of Positive Symptoms–Parkinson’s Disease (SAPS-PD).

Results The modified intention-to-treat population included 38 patients (SEP-363856, n=24; placebo, n=14). Mean (SD) baseline SAPS-PD total score was 14.6 (7.19) and Mini-Mental State Examination (MMSE) score was 24.3 (4.63). Numerical improvements in SAPS-PD total scores for SEP-363856 versus placebo occurred as early as week 1; least-squares mean (SE) change from baseline at week 6 was -2.5 (1.62) versus -1.4 (2.06; P=0.681). Remission (≥100% improvement in SAPS-PD total score) occurred in 25% versus 0% of patients. Greater effects were seen for SAPS-PD Hallucinations subscale score [-3.6 (1.07) versus -1.9 (1.35; P=0.339)] and SAPS-PD total score in patients with baseline MMSE score ≤24 [-5.2 (2.81) versus -2.1 (3.00; P=0.460)]. Unified Parkinson’s Disease Rating Scale Parts II and III demonstrated no change at 6 weeks in motor parkinsonism. Neuropsychiatric Inventory-Hallucination subscale but not Clinical Global Improvement–Severity scores showed similar improvement. Adverse events (occurring in ≥15%) with SEP-363856 versus placebo included hallucinations (24% vs 14%), confusional state (20% vs 14%), dizziness (16% vs 7%), and falls (12% vs 21%). Incidence of CNS adverse events appeared dose-related.

Conclusions In this proof-of-concept study, improvements across several scales without worsening motor parkinsonism suggest that SEP-363856 may provide a novel non-D₂-receptor blocking treatment for PDP, particularly for patients with cognitive impairment. SEP-363856 was generally well-tolerated. Additional studies are warranted.

Authors/Disclosures
Stuart H. Isaacson, MD, FAAN (Parkinson's Dis & Mov Dis Ctr of Boca Raton) PRESENTER	The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Acadia. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sunovion. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for acorda. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Supernus. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neurocrine. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Kyowa. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for adamas. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Teva. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neuroderm. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbvie. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for amneal. Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Teva. Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Neurocrine. Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for adamas. Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Lundbeck. Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Supernus. Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Acadia. Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Acorda. Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Amneal. Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Abbvie.
Mark A. Goldstein, MD, FAAN (JEM Research)	Dr. Goldstein has received personal compensation for serving as an employee of Headlands Research. Dr. Goldstein has received stock or an ownership interest from Headlands Research.
Rajesh Pahwa, MD, FAAN (University of Kansas Medical Center)	Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbott. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for AbbVie. Dr. Pahwa has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for ACADIA. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Acorda. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amneal. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Kyowa. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurocrine. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Supernus. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Allevion. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Insightec. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Jaaz. Dr. Pahwa has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neuroderm. Dr. Pahwa has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Photopharmics. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sage. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Fasikl. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genetech. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merz. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sun Biopharma. The institution of Dr. Pahwa has received research support from Abbott. The institution of Dr. Pahwa has received research support from Abbvie. The institution of Dr. Pahwa has received research support from Biogen. The institution of Dr. Pahwa has received research support from Biohaven. The institution of Dr. Pahwa has received research support from EIP. The institution of Dr. Pahwa has received research support from Amneal. The institution of Dr. Pahwa has received research support from Parkinson Foundation. The institution of Dr. Pahwa has received research support from Roche. The institution of Dr. Pahwa has received research support from Sage. The institution of Dr. Pahwa has received research support from Sun Pharma. The institution of Dr. Pahwa has received research support from Theranexus. The institution of Dr. Pahwa has received research support from Theravance. The institution of Dr. Pahwa has received research support from Voyager. The institution of Dr. Pahwa has received research support from Neuroderm. The institution of Dr. Pahwa has received research support from Annovis. The institution of Dr. Pahwa has received research support from Ask Bio. The institution of Dr. Pahwa has received research support from Blue Rock. The institution of Dr. Pahwa has received research support from Cerevance. The institution of Dr. Pahwa has received research support from Fasikl. The institution of Dr. Pahwa has received research support from Praxis. The institution of Dr. Pahwa has received research support from Scion. The institution of Dr. Pahwa has received research support from UCB.
Carlos Singer, MD (University of Miami)	Dr. Singer has nothing to disclose.
Kevin Klos, MD (The Movement Disorder Clinic of Oklahoma)	The institution of Dr. Klos has received research support from Sunovion. The institution of Dr. Klos has received research support from Roche. The institution of Dr. Klos has received research support from Impax. The institution of Dr. Klos has received research support from Prilenia. The institution of Dr. Klos has received research support from Enterin.
	No disclosure on file
David Crandall	David Crandall has received personal compensation for serving as an employee of Sunovion Pharmaceuticals Inc..
	No disclosure on file