Abstract: Iloperidone is a mixed D2/5-HT2 antagonist in development for treatment of schizophrenia. This trial aimed to evaluate the efficacy and safety of a fixed dose of iloperidone in patients with acute exacerbations of schizophrenia. This randomized, placebo-controlled, multicenter study comprised a 1-week titration period and a 3-week double-blind maintenance period. Eligible patients (n = 593) were randomized to iloperidone 24 mg/d, ziprasidone 160 mg/d as an active control, or placebo. Primary efficacy variable was change from baseline in the Positive and Negative Syndrome Scale Total (PANSS-T) score, using a mixed-effects model repeated measures analysis. Iloperidone demonstrated significant reduction versus placebo on the PANSS-T score (P< 0.01). Significant improvement versus placebo was also demonstrated with ziprasidone (P < 0.05). Compared with ziprasidone, iloperidone was associated with lower rates of many adverse events (AEs) that are particularly troublesome with antipsychotics, including sedation, somnolence, extrapyramidal symptoms, akathisia, agitation, and restlessness; iloperidone was associated with higher rates of weight gain, tachycardia, orthostatic hypotension, dizziness, and nasal congestion as reported as an AE. Most AEs were mild to moderate. A similar amount of QT prolongation was observed with both active treatments, although no patient had a treatment-emergent postbaseline corrected QT interval of 500 msec or greater. The incidence of clinically relevant changes in laboratory parameters was comparable between iloperidone and ziprasidone. Iloperidone was associated with a low incidence of extrapyramidal symptoms. Overall, there was improvement in akathisia with iloperidone treatment. Iloperidone treatment was effective, safe, and well tolerated in patients with acute exacerbation of schizophrenia.
*University of Florida, Gainesville, FL; †Florida Clinical Research Center, LLC, Maitland, FL; ‡University of California San Diego, CA; §Quintiles CNS Therapeutics, San Diego, CA; ∥Center for Cognitive Medicine, University of Illinois Medical Center, Chicago, IL; and ¶Vanda Pharmaceuticals Inc, Rockville, MD.
Received December 14, 2007; accepted after revision January 19, 2008.
This study was supported by Vanda Pharmaceuticals Inc. This clinical study complied with the current laws of the countries in which they were performed.
Address correspondence and reprint request to Andrew J. Cutler, MD, Florida Clinical Research Center, 2300 Maitland Center Parkway, Suite 230, Maitland, FL 32751. E-mail: firstname.lastname@example.org.