A translational approach to evaluate the efficacy and safety of the novel AMPA receptor positive allosteric modulator org26576 in adult attention-deficit/hyperactivity disorder. It has been posited that glutamate dysregulation contributes to the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). Modulation of glutamate neurotransmission may provide alternative therapeutic options. The novel 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid receptor positive allosteric modulator Org26576 was investigated with a translational approach including preclinical and clinical testing. Neonatal rat 6-hydroxydopamine lesion-induced hyperactivity was used as preclinical model. Seventy-eight ADHD adults entered a multicenter, double-blind, placebo-controlled, two-period
Examination of Org26576, an AMPA receptor positive allosteric modulator, in patients diagnosed with major depressive disorder: an exploratory, randomized, double-blind, placebo-controlled trial. Org26576 acts by modulating ionotropic AMPA-type glutamate receptors to enhance glutamatergic neurotransmission. The aim of this Phase 1b study (N=54) was to explore safety, tolerability , pharmacokinetics, and pharmacodynamics of Org26576 in depressed patients. Part I (N=24) evaluated the maximum tolerated dose (MTD) and optimal titration schedule in a multiple rising dose paradigm (range 100 mg BID to 600 mg BID); Part II (N=30) utilized a parallel groups design (100 mg BID, 400 mg BID, placebo) to examine all endpoints over a 28-day dosing period. Based on the number of moderate intensity
Maximum tolerated dose evaluation of the AMPA modulator Org26576 in healthy volunteers and depressed patients: a summary and method analysis of bridging research in support of phase II dose selection. A key challenge to dose selection in early central nervous system (CNS) clinical drug development is that patient tolerability profiles often differ from those of healthy volunteers (HVs), yet HVs in the target population prior to full-scale proof-of-concept trials. Org26576 is an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor positive allosteric modulator that acts by modulating ionotropic AMPA-type glutamate receptors to enhance glutamatergic neurotransmission. In preparation for phase II efficacy trials in major depressive disorder (MDD), two separate phase I trials were
-8777 (Org26576, SCH 900777) in adult subjects with Attention-Deficit/Hyperactivity Disorder (ADHD). MK-8777 or placebo will be administered in a crossover fashion for two 3-week treatment periods. The two 3-week treatment periods will be separated by a 2-week placebo washout period.The primary objective is to compare the efficacy of various doses of MK-8777 to that of placebo in the treatment Official Title: A Double Blind, Placebo Controlled, Randomized, Two Period 4-Arm Trial to Investigate the Dose-Related Efficacy and Safety of Org26576 in Adults With Attention-Deficit/Hyperactivity Disorder (ADHD) Actual Study Start Date : April 1, 2008
Trial to Determine the Maximum Tolerated Dose (MTD) Based on Safety and Tolerability, of Org26576 in Participants With Major Depressive Disorder (174001/P05704/MK-8777-001)