Abstract Details

Title Exposure-response (ER) and Clinical Trial Simulations for Efficacy of Ecopipam in Adults and Pediatrics with Tourette’s Syndrome (TS)

Topic Movement Disorders

Presentation(s) P2 - Poster Session 2 (11:45 AM-12:45 PM)

Poster/Presentation
Number 16-001

Objective To characterize the E-R relationship of ecopipam in TS patients, to identify any differences between adult and pediatric patients, and to perform clinical trial simulations to add to the weight of efficacy in adults with TS.

Background Ecopipam is a first-in-class selective dopamine-1 receptor (D1R) antagonist being investigated for treatment of TS. Ecopipam is primarily metabolized to ecopipam glucuronide (E-G), with a minor metabolite, EBS-101-40853 (EBS) and its glucuronide conjugate (EBS-G). EBS and E-G are also active but much less potent at the D1R than ecopipam.

Design/Methods A pre-specified population pharmacokinetics (PopPK), exposure-response (E-R), and clinical trial simulation plan was utilized throughout the clinical development of ecopipam. An E-R model for efficacy was developed using data from Phase 2b study EBS-101-CL-001 (RCT) and Phase 3 study EBS-101-TD-301 (RWD). Exposure was defined as the combined active exposure (ecopipam, EBS, and E-G), corrected for differences in potency, protein binding, and brain penetration predicted using PopPK. Response was defined as a ≥25% improvement from baseline in the Yale Global Tic Severity Scale – Total Tic Score (YGTSS-TTS) at Week 8. Clinical trial simulations (n=500) were conducted assuming a RCT study (50 adults/50 pediatrics on ecopipam, 50 adults/ 50 pediatrics on placebo. Success was defined as a p <0.017 AND a probability of response active-placebo of ≥15%, ≥20%, or ≥25%.

Results Combined active exposure, study type (whether RCT or RWD) and age group (<18, ≥18 years) were important covariates describing the probability of being a responder. Clinical trial simulations showed that the probability of successfully demonstrating efficacy (active-placebo ≥ 20%) and clinically meaningful benefit for ecopipam is ≥ 90% if an RCT was conducted in adult and pediatric patients with TS.

Conclusions PopPK, E-R, and clinical trial simulations add to the weight of evidence for the efficacy of ecopipam in pediatrics and adults with TS.

Authors/Disclosures
Stephen Wanaski, PhD (Paragon Biosciences) PRESENTER	Dr. Wanaski has received personal compensation for serving as an employee of Paragon Biosciences. Dr. Wanaski has or had stock in Paragon Biosciences.Dr. Wanaski has or had stock in Emalex Biosciences.
Soha Freidy, PharmD	Dr. Freidy has received personal compensation for serving as an employee of Allucent, LLC.,.
Patricia Rice (Emaxlex Biosciences)	Patricia Rice has received personal compensation for serving as an employee of 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.
Virginia Schmith, PhD	Dr. Schmith has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Emalex Biosciences.

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