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.

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.

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.

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