Ulotaront, a Trace Amine-Associated Receptor 1/Serotonin 5-HT 1A Agonist, in Patients With Parkinson Disease Psychosis

作者：Stuart Isaacson, Mark Goldstein, Rajesh Pahwa, Carlos Singer, Kevin J. Klos, Michael J. Pucci, Yi Zhang, David Crandall, Kenneth S. Koblan, Bradford Navia, for the Parkinson's Psychosis TAAR1 Study Group · 发表于：Neurology Clinical Practice · 年份：2023 · DOI：10.1212/cpj.0000000000200175 · 被引用次数：23 · 研究领域：Neurotransmitter Receptor Influence on Behavior、Parkinson's Disease Mechanisms and Treatments、Pharmacological Receptor Mechanisms and Effects

Background and Objectives Ulotaront (SEP-363856) is a trace amine-associated receptor 1 agonist with 5-HT 1A receptor agonist activity currently in phase 3 clinical development for the treatment of schizophrenia. In this exploratory, flexibly dosed study, ulotaront was evaluated for the treatment of Parkinson disease psychosis (PDP). Methods Patients with PDP requiring antipsychotic therapy were randomized, double-blind to ulotaront (25, 50, or 75 mg/d) or placebo. Mixed Model for Repeated Measures was used to assess change from baseline in the Scale for the Assessment of Positive Symptoms for Parkinson Disease (SAPS-PD) at 6 weeks (primary end point). Results The efficacy analysis sample comprised 38 patients (ulotaront, n = 24; placebo, n = 14). SAPS-PD total scores were numerically reduced in ulotaront-treated vs placebo-treated patients from week 1 to week 6: Least squares mean (95% confidence interval) difference in change from baseline at week 6 was −1.1 (−6.5, 4.3, p = 0.681). PDP symptom complete remission (≥100% improvement [reduction] from baseline in SAPS-PD total score) was observed in 25% of ulotaront-treated vs 0% of placebo-treated patients. SAPS-PD and Neuropsychiatric Inventory hallucinations subscales were numerically reduced vs placebo, and SAPS-PD total scores were reduced in patients with greater cognitive impairment (baseline Mini-Mental State Examination [MMSE] scores ≤24). Ulotaront improved Scales for Outcomes in Parkinson Disease Sleep Scale ...