Abstract Details

Title SYN120 (a dual 5-HT6/5-HT2A antagonist) study to evaluate safety, tolerability, and efficacy in Parkinson’s disease dementia (SYNAPSE): Phase 2a study results

Topic Movement Disorders

Presentation(s) S4 - Clinical Trials in Movement Disorders (1:44 PM-1:55 PM)

Poster/Presentation
Number 005

Background SYN120 is an antagonist of serotonin receptors (5-HT₆and 5-HT_2A) shown to improve cognition in preclinical models.

Objective To evaluate the safety and preliminary efficacy of SYN120 in patients with Parkinson's disease dementia (PDD).

Design/Methods This phase 2a, randomized (1:1), double-blind, placebo-controlled, parallel-group, 16-week study was conducted at 20 Parkinson Study Group sites in PDD patients taking a cholinesterase inhibitor. Eligible patients (i.e., meeting UKPDSBBC for PD) were randomized to SYN120 100 mg daily or placebo. Adverse events (AEs), Unified Parkinson’s Disease Rating Scale (UPDRS) scores and study discontinuation were tracked to assess safety and tolerability. The primary and key secondary efficacy outcomes were the Computerized Drug Research Cognition Battery (CDR) Continuity of Attention (COA; sustained attention) and CDR Quality of Episodic Memory (QEM). Other secondary outcomes included: Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-cog), and Alzheimer’s Disease Cooperative Study-Clinician’s Global Impression of Change (ADCS-CGIC).

Results

A total of 82 patients were randomized and started study medication; 5 terminated prior to post-baseline COA assessment, resulting in modified ITT groups of SYN120=36, placebo=41. Treatment groups were well matched at baseline. From baseline to week 16, no significant effect of SYN120 was observed on CDR COA (SYN120 vs placebo difference estimate [DE]= –4.0; P=0.13), CDR QEM (DE=7.49; P=0.52), ADAS-cog (DE= –0.36; P=0.82), and ADCS-CGIC (–0.43; P=0.07). Motor symptoms (UPDRS Part III) worsened (DE=4.81; P=0.01). AEs were experienced by 74% SYN120 and 77% placebo participants, 11% were serious (both groups), and 16% SYN120 and 14% placebo participants discontinued study treatment due to AEs. Although infrequent, incidence of nausea, vomiting, and visual hallucinations were two-fold higher with SYN120.

Conclusions SYN120 did not improve cognition in patients with PDD, but it may have improved cognition-based daily function. SYN120 was generally well tolerated, however, a worsening in motor symptoms was observed.

Authors/Disclosures
Hubert H. Fernandez, MD, FAAN (Center for Neurological Restoration, Cleveland Clinic) PRESENTER	Dr. Fernandez has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Fernandez has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amneal. Dr. Fernandez has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Intrance. Dr. Fernandez has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Fernandez has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbvie. Dr. Fernandez has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Fernandez has received publishing royalties from a publication relating to health care. Dr. Fernandez has received personal compensation in the range of $10,000-$49,999 for serving as a Steering Committee/Advisory Committee Member with Parkinson Study Group.

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