TARGET ENGAGEMENT OF INVESTIGATIONAL AGENTS IN PSPP

Psychogenics, Inc., Tarrytown NY

Investigators

Abstract

This study is part of the NIH’s Helping to End Addiction Long-term (HEAL) initiative to speed scientific solutions to understand the basis of pain and enhance clinical pain management. The Contractor shall provide profiling of potentially viable assets submitted through the PSPP. NINDS will send assets to the Contractor in a blinded fashion (Contractor is blinded to structure, target, asset owner), and the Contractor shall perform evaluation through the progressive testing funnel established in collaboration with NINDS staff and the PSPP External Consultant Board (ECB). The evaluation will entail (1) in vitro studies for determining functional activity at known human targets of drugs of abuse, and safety signals(2) in vitro models of pain, (3) testing models of tolerability and/or side effect liability shall also be performed to determine therapeutic index (4) series of acute and chronic pain models. (5) Additional testing in models of abuse liability, in vivo, shall also be investigated to evaluate the assets for addictive potential. The Contractor shall provide resources and expertise in not only the execution of existing models, but also in establishing new in vivo pain models to create a standardized panel of preclinical pain models and endpoints that shall be used to evaluate potential efficacy as well as the side effects and abuse liability of Contributor-submitted investigational agents. The Contractor shall evaluate the efficacy, pharmacokinetics, side effects and abuse liability of new investigational agents, perform in vitro pharmacological profiling and determine target selectivity, execute formulation research studies and establish Absorption, Distribution, Metabolism and Excretion (ADME) profiles of candidate agents submitted to the NINDS by Contributors. The Contractor in their own facilities or through subcontractors shall also provide the complete array of in vitro and in vivo assays to evaluate the potential side effects, drug abuse liability, in vitro pharmacological profiling and target selectivity, ADME profiling, formulation research studies, and pharmacokinetic studies of the investigational agents.