SBIR Phase 1 preclinical studies demonstrate the efficacy of our proprietary compound, PD2005, for treating Attention Deficit/Hyperactivity Disorder (ADHD). PD2005 is a selective dopamine (DA) transport inhibitor that P2D is developing for the treatment of ADHD. The American Academy of Pediatrics identifies the non-selective DA transport inhibitors methylphenidate and amphetamine as the only approved first-line treatments for ADHD. These first-line treatments are Schedule II drugs of abuse administered primarily to children. In contrast, PD2005 demonstrates no abuse potential in studies conducted at the National Institute on Drug Abuse (NIDA). The long term goal of the proposed studies is to develop a safe and effective ADHD treatment with limited abuse potential (non-Scheduled or Schedule IV). PD2005 is a benztropine analog. Benztropine is a high affinity DA transport inhibitor found safe and effective by the FDA and in clinical use for over 30 years. Benztropine demonstrates no significant abuse potential and is a non-Scheduled drug. Unfortunately, benztropine's clinically significant anti- cholinergic side effects preclude its use as an ADHD treatment. Extensive lead optimization studies have been performed with our proprietary library of benztropine analogs. Preliminary studies indicate that our lead compound, PD2005, demonstrates no anti-cholinergic side effects including the anti- cholinergic cardiovascular side effect (tachycardia) characteristic of benztropine. Additionally, a PD2005 safety and toxicology study was commissioned and performed by the US Food and Drug Administration's (FDA) Center for Drug Evaluation (CDER). No PD2005 carcinogenicity, teratogenicity, mutagenicity or toxicology in major organ systems was found in these FDA computational studies. These data highlight the improved safety profile of PD2005 SBIR Phase 1 studies demonstrate that PD2005 is as effective as current first-line ADHD treatments. First, PD2005 is as effective as first-line ADHD treatments at improving working memory, a core ADHD symptom, in a well accepted preclinical ADHD model. Second, PD2005 is as effective as first-line ADHD treatments at improving sustained attention, also a core symptom of ADHD, in another well accepted preclinical ADHD model. Additional Preliminary Studies indicate that PD2005 is effective after oral administration. The proposed studies are the FDA safety and toxicology studies required for submission of a PD2005 Investigational New Drug (IND) application which would allow PD2005 use in humans when approved. All proposed studies will be compiled in Study Reports, submitted to the FDA and discussed with the FDA in a face-to-face Pre-IND meeting to assess PD2005 compliance with FDA ICH M3 IND guidelines.
The American Academy of Pediatrics identifies methylphenidate and amphetamine as the only approved first-line treatments for Attention Deficit/Hyperactivity Disorder (ADHD). These first-line treatments are Schedule II drugs of abuse administered primarily to children. The goal of the proposed studies is to develop a new ADHD treatment as effective as current first-line treatments but with reduced side effects including no abuse potential.