Alexza Pharmaceuticals, Inc. has initiated its first phase III clinical trial with AZ-004 (Staccato loxapine), an inhalation product candidate being developed for the treatment of acute agitation in patients with schizophrenia or bipolar disorder.

Alexza said the novel, non-invasive nature and rapid pharmacokinetic (PK) properties resulting from inhaled loxapine administration via the Staccato system have the potential to make AZ-004 a viable product to treat acute agitation. AZ-004 is being developed through Symphony Allegro, a product development partnership formed between Alexza and Symphony Capital, LLC.

"We are excited to be initiating our AZ-004 NDA plan with this first phase III clinical trial," said Thomas B. King, president and CEO, Alexza. "The results we have seen to date with AZ-004 have been promising and we look forward to enrolling the planned phase III clinical trials as quickly as possible. This is a transitional year in our history as we move into the early commercial planning for the manufacturing, regulatory submissions and potential sales and marketing of AZ-004."

The first AZ-004 phase III clinical trial is designed to enrol approximately 300 schizophrenic patients with acute agitation at 25 US clinical centres. The trial is an in-clinic, multi-centre, randomized, double-blind, placebo-controlled study and will test AZ-004 at two dose levels, 5 and 10 mg. Patients may receive up to 3 doses of study drug in a 24-hour period, depending on their clinical status.

The primary endpoint for the study is the change from baseline in the PANSS (Positive and Negative Symptom Scale) Excited Component (also known as PEC) score, measured at 2 hours after the first dose. Various assessments of a patient's agitation state will be conducted at serial time points using standard agitation scales over the first 4-hour post-dose time period, with follow-up assessments at the end of the 24-hour study period. Side effects will be recorded throughout the 24-hour period.

A second phase III clinical trial is projected to begin in Q3 2008. The design of the second study will be similar to the first trial, except that the patient population will be patients with bipolar disease.

Acute agitation, characterised by unpleasant arousal, tension, irritability and hostility, is one of the most common and severe symptoms of many major psychiatric disorders, including schizophrenia and bipolar disorder. According to the National Institute of Mental Health (NIMH), schizophrenia afflicts about 2.4 million people in the United States and bipolar disease affects about 5.7 million American adults. We believe over 90 per cent of these patients will experience agitation during their lifetime and that about 70 per cent of those who experience agitation will have one to six episodes per year.

AZ-004 is the combination of Alexza's proprietary Staccato system with loxapine, a drug belonging to the class of compounds known generally as atypical antipsychotics. The Staccato system technology is a hand-held, chemically-heated, single dose inhaler designed to generate and deliver excipient-free drug aerosol for deep lung delivery that results in IV-like pharmacokinetics. Alexza has completed three clinical trials with AZ-004, including a 50 subject phase I study, a 129 patient phase II study and a 32 patient multiple-dose tolerability and PK study in schizophrenic patients.

Alexza Pharmaceuticals is an emerging specialty pharmaceutical company focused on the development and commercialisation of novel, proprietary products for the treatment of acute and intermittent conditions.