Drug Approval Package from the US Food and Drug Administration available at http://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022192s000TOC.cfm.
DATA SYNTHESIS: The Drug Approval Package contains several different sections that describe both the preclinical (animal) and the clinical (human) studies conducted that led to the approval of
iloperidone, a second-generation
antipsychotic medication. Most of this information has not been published in the peer-reviewed literature and much of it had not been previously publicly available.
Iloperidone's indication for the acute treatment of
schizophrenia in adults is supported by two of the four principal registration studies completed by the manufacturer. The documents made available reveal that there was disagreement between the Food and Drug Administration (FDA) and the manufacturer as to which study was considered 'positive' for
iloperidone. There was additional controversy surrounding the appropriateness of combining patients with
schizophrenia and
schizoaffective disorder in the same study. Questions were also raised by the FDA about the relative efficacy of
iloperidone vs. other
antipsychotics; the need for an initial titration period was offered as a possible explanation as to why
risperidone appeared to have superior efficacy. Moreover, there was disagreement as to what constitutes an appropriate study to test the long-term efficacy of an
antipsychotic. Additional information is made available regarding the safety and tolerability of
iloperidone, with the FDA acknowledging an overall attractive profile that includes less
akathisia and extrapyramidal symptoms than other agents in its class. Of potential clinical utility are the results from FDA analyses of patients where clinical variables shifted from the normal to abnormal range.
CONCLUSIONS: