P02-05 - Inhaled Loxapine (AZ-004, Staccato Loxapine) for Rapid and Acute Treatment of Agitation in Patients with Schizophrenia or Bipolar Disorder

Abstract

Objectives

Current treatments for agitation in schizophrenia or bipolar disorder (BD) have limitations in onset of action, invasiveness and tolerability. AZ-004 (Staccato loxapine) is a rapidly acting inhaled treatment designed for acute treatment of agitation delivering drug aerosol to the deep lung for rapid systemic absorption with intravenous-like kinetics. The objective was to evaluate the efficacy and safety of AZ-004 in the acute treatment of agitation in schizophrenia and BD.

Methods

Two randomized, double-blind, placebo-controlled trials included consenting male and female adults, 18-65 years old with DSM-IV-defined schizophrenia (N=344) or BD type 1 or mixed (314) who presented with clinically relevant agitation. Patients received a single inhalation of 5 or 10mg AZ-004 or placebo in a clinical setting with up to 2 additional doses within 24 hours if required. The primary efficacy endpoint was the absolute change in Positive and Negative Syndrome Scale Excited Component score from baseline to 2 hours following treatment.

Results

In each trial, both 5 and 10mg AZ-004 were significantly superior to placebo for the primary endpoint (P< 0.001 for each dose in each trial). Significant improvements were noted for each AZ-004 dose versus placebo at all timepoints from 10 minutes through 24 hours. Clinical Global Impression-Improvement (CGI-I) at 2 hours post-dose and CGI-I responder analysis were statistically significant for each AZ-004 dose vs. placebo in both studies. Adverse events observed most often for all treatments were dysgeusia, dizziness, and sedation.

Conclusions

AZ-004 produced rapid and significant improvement in treating agitation in BD or schizophrenia patients.