Source: DGNews  |  Posted 2 years ago

By Roberta Friedman, PhD

SAN FRANCISCO -- May 30, 2009 -- An older atypical antipsychotic agent delivered by a new device to rapidly generate an aerosol can effectively calm agitated patients with bipolar disorder or schizophrenia, according to findings from 2 randomised phase 3 studies, presented here at the 162nd Annual Meeting of the American Psychiatric Association (APA).

As compared with placebo, loxapine delivered by the device provided an intravenous (IV)-like, rapid response compared with placebo.

Robert Fishman, MD, Alexza Pharmaceuticals, Inc., Mountain View, California, said in a poster presentation on May 20 that within 10 minutes, the loxapine-treated patients with bipolar disorder, compared with placebo-treated patients, scored significantly lower (P < .0001) on the Positive and Negative Symptom Scale, Excited Component (PANSS-EC).

For the study, a total of 314 patients received a single inhalation of placebo, loxapine 5 mg, or loxapine 10 mg in an inpatient treatment facility. Up to 2 additional doses of study drug were allowed beyond 2 hours if required.

The palm-sized delivery system (Staccato) activates with the warmth of a person’s breath to deliver pure drug as a vapour, entering the respiratory tract within 1 second. Dr. Fishman said that extensive testing shows that the device delivers adequate amounts of drug consistently. He did agree that patient cooperation is needed for proper use.

The response was sustained over 24 hours. Dr. Fishman added that a tertiary endpoint was met in the study in that the patients treated with active drug did not require rescue with benzodiazepines.

“This particular system is very forgiving in terms of inhalation effort,” Dr. Fishman said, noting that three-quarters of the patients were smokers. Pharmacokinetics show it entering the bloodstream consistently, he said, “as long as you take a reasonable inhalation.”

A transient bad taste results from a local effect of the delivery method. No serious events occurred, he said, “it is very clean on the respiratory side. There were no surprises.”

The drug did not sedate, but instead, induced “mild calmness,” Dr. Fishman explained.

James Cassella, PhD, of Alexza Pharmaceuticals, reported similar findings in 344 patients with schizophrenia aged 18 to 65 years who were randomised to placebo, or loxapine 5 or 10 mg inhaled via the same method.

Receiving a single inhalation of loxapine with the device resulted in significant improvement in symptoms of agitation within 10 minutes for those who received 10 mg (P < .0001), and for those who had the lower dose as well (P < .0003). The improvement over placebo remained significant over 24 hours for the higher dose.

The primary endpoint was absolute change in the PANSS-EC. Scoring on the scale includes symptoms of excitement, lack of cooperation, impulse control, tension, and hostility.

Entry criteria included the ability to give informed consent as well as meeting the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria for schizophrenia.

Sedation was the same as with placebo, Dr. Cassella said. There was less repeat dosing with the trial, and very little extrapyramidal side effect, he added.

Funding for both studies was provided by Alexza Pharmaceuticals.

[Presentation Title: Inhaled Loxapine Rapidly Improves Acute Agitation in Patients With Bipolar Disorder. Abstract NR7-006; and Inhaled Loxapine Rapidly Improves Acute Agitation in Schizophrenic Patients. Abstract NR7-005]