Abstract Details

Title Effect of Ecopipam, a Selective Dopamine-1 Receptor Antagonist, on Tic Characteristics as Assessed by the YGTSS: Results from the Phase IIb (D1AMOND) Randomized, Double-blind, Placebo-controlled Clinical Trial in Tourette Syndrome

Topic Movement Disorders

Presentation(s) S30 - Movement Disorders: Clinical Trials in Movement Disorders (2:36 PM-2:48 PM)

Poster/Presentation
Number 009

Background Whether features of tics are more or less responsive to treatment is unknown. Ecopipam, a first-in-class selective dopamine-1 receptor antagonist, is in development for TS. In a phase IIb trial, YGTSS-TTS was reduced by 30% (p=0.01) from baseline to week 12 for the ecopipam group. No weight gain, or drug-induced movement disorders were identified. Headache (9.2%), fatigue (6.6%), somnolence (6.6%), insomnia (5.3%), and restlessness (5.3%) were the most common adverse reactions.

Objective

Assess the effect of ecopipam treatment on motor and phonic/vocal tic characteristics: number, frequency, intensity, complexity, and interference comprising the Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS) in subjects ages 6 to <18 years with Tourette Syndrome (TS).

Design/Methods In the trial, subjects were randomly assigned 1:1 to ecopipam (n =76) or placebo (n = 77). This post-hoc analysis examines YGTSS-TTS characteristics at baseline, weeks 4, 6, 8, and 12, utilizing a mixed model for repeated measures analysis of change from baseline.

Results For motor tics, the largest reductions were in intensity scores [ecopipam – placebo LS Means difference of -0.48 (95% confidence interval -0.79 to -0.17); p < 0.01] followed by number, frequency, and interference (ecopipam – placebo differences ranging from -0.34 to -0.43; all p < 0.05). For phonic tics, the largest reduction was in complexity scores [ecopipam – placebo LS Means difference of -0.48 (95% confidence interval -0.91 to -0.06); p = 0.02]. Differences in reduction in motor tic complexity scores and all other phonic tic subscores fell short of statistical significance.

Conclusions Ecopipam significantly reduced both motor and phonic tics. Of the 5 motor tic characteristics, only complexity was not significantly reduced. Of phonic tic characteristics, only complexity was significantly reduced. Lower baseline phonic tics scores may limit power to identify statistical differences. The current analysis increases our understanding of ecopipam’s effects on tic characteristics.

Authors/Disclosures
Donald Gilbert, MD, FAAN (Cincinnati Children's Hospital Med. Ctr.) PRESENTER	Dr. Gilbert has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PTC Therapeutics. Dr. Gilbert has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Illumina. Dr. Gilbert has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Emalex Biosciences. The institution of Dr. Gilbert has received research support from NIMH. The institution of Dr. Gilbert has received research support from Emalex Biosciences. The institution of Dr. Gilbert has received research support from PTC Therapeutics. The institution of Dr. Gilbert has received research support from Department of Defense. Dr. Gilbert has received publishing royalties from a publication relating to health care. Dr. Gilbert has received publishing royalties from a publication relating to health care. Dr. Gilbert has received personal compensation in the range of $0-$499 for serving as a Medical Second Opinion Expert with Teldoc/Advanced Medical. Dr. Gilbert has received personal compensation in the range of $10,000-$49,999 for serving as a Medical Expert with Department of Health and Human Services/Vaccine Injury Compensation Program.
George Karkanias, PhD (Emalex Biosciences, Inc.)	Dr. Karkanias has received personal compensation for serving as an employee of Emalex Biosciences, Inc.
Frederick E. Munschauer III, MD, FAAN (FEMC)	Dr. Munschauer has received personal compensation for serving as an employee of Emalex Biosciences. Dr. Munschauer has stock in Emalex Biosciences.
Stephen Wanaski, PhD (Paragon Biosciences)	Dr. Wanaski has received personal compensation for serving as an employee of Paragon Biosciences. Dr. Wanaski has stock in Paragon Biosciences. Dr. Wanaski has stock in Emalex Biosciences.
Timothy Cunniff, PharmD	Dr. Cunniff has received personal compensation for serving as an employee of Paragon Biosciences. Dr. Cunniff has stock in Harmony Biosciences. Dr. Cunniff has stock in Emalex Biosciences.