Four-week, double-blind, placebo- and ziprasidone-controlled trial of iloperidone in patients with acute exacerbations of schizophrenia.

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.

• Authors: Andrew J Cutler, Amir H Kalali, Peter J Weiden, Jennifer Hamilton, Curt D Wolfgang
• Journal: Journal of clinical psychopharmacology (J Clin Psychopharmacol) Vol. 28 Issue 2 Suppl 1 Pg. S20-8 (Apr 2008) ISSN: 0271-0749 [Print] United States
• PMID: 18334909 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antipsychotic Agents
• Isoxazoles
• Piperazines
• Piperidines
• Thiazoles
• ziprasidone
• iloperidone

Topics

• Acute Disease
• Adolescent
• Adult
• Aged
• Antipsychotic Agents (administration & dosage, adverse effects, therapeutic use)
• Double-Blind Method
• Drug Administration Schedule
• Female
• Humans
• Isoxazoles (administration & dosage, adverse effects, therapeutic use)
• Male
• Middle Aged
• Piperazines (administration & dosage, adverse effects, therapeutic use)
• Piperidines (administration & dosage, adverse effects, therapeutic use)
• Prospective Studies
• Schizophrenia (drug therapy)
• Thiazoles (administration & dosage, adverse effects, therapeutic use)
• Treatment Outcome