title: Use of translational pharmacodynamic biomarkers in early-phase clinical studies for schizophrenia.
abstract: Schizophrenia is a severe mental disorder characterized by cognitive deficits, and positive and negative symptoms. The development of effective pharmacological compounds for the treatment of schizophrenia has proven challenging and costly, with many compounds failing during clinical trials. Many failures occur due to disease heterogeneity and lack of predictive preclinical models and biomarkers that readily translate to humans during early characterization of novel antipsychotic compounds. Traditional early-phase trials consist of single- or multiple-dose designs aimed at determining the safety and tolerability of an investigational compound in healthy volunteers. However, by incorporating a translational approach employing methodologies derived from preclinical studies, such as EEG measures and imaging, into the traditional Phase I program, critical information regarding a compound's dose-response effects on pharmacodynamic biomarkers can be acquired. Furthermore, combined with the use of patients with stable schizophrenia in early-phase clinical trials, significant 'de-risking' and more confident 'go/no-go' decisions are possible.
authors: Parexel International, Glendale, CA, USA.
authors: Brett A
authors: BA
authors: English
authors: Kelan
authors: K
authors: Thomas
authors: Jack
authors: J
authors: Johnstone
authors: Adam
authors: A
authors: Bazih
authors: Lev
authors: L
authors: Gertsik
authors: Larry
authors: L
authors: Ereshefsky
mesh_terms: D014150:Antipsychotic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001519:Behavior; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D002986:Clinical Trials as Topic; D003071:Cognition; D042241:Early Diagnosis; D004569:Electroencephalography; D006801:Humans; D008279:Magnetic Resonance Imaging; D049268:Positron-Emission Tomography; D012559:Schizophrenia / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D015415:Biomarkers