Staccato Loxapine in Agitation (Proof of Concept)

A Multi-center, Randomized, Double-blind, Placebo-controlled, Single Dose Efficacy and Safety Study of StaccatoTM Loxapine for Inhalation in Schizophrenic Patients With Agitation.

The purpose of this study is to assess efficacy and safety of Staccato Loxapine in the treatment of acute agitation in schizophrenic patients. The study will be conducted in 120 agitated schizophrenic patients - either newly admitted to a hospital setting or a research unit for acute agitation or already in hospital for chronic underlying conditions. Patients meeting entry criteria will be randomized to one of two doses of Staccato Loxapine or to Staccato Placebo. Following administration of study drug, assessment of agitation state will be conducted at serial time points using standard agitation scales over a 24 hour period.

Inclusion Criteria:

1. Male and female patients between the ages of 18 to 65 years, inclusive.
2. Patients who have met DSM-IV criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder.
3. Patients who are judged to be clinically agitated at Baseline with a total score of ≥ 14 on the 5 items (poor impulse control, tension, hostility, uncooperativeness, and excitement) comprising the PANSS Excited Component (PEC).
4. Patients who have a value of ≥ 4 (out of 7) on at least 1 of the 5 items on the PANSS Excited Component.
5. Patients who read and understand English and provide written informed consent.
6. Patients who are in good general health prior to study participation as determined by a detailed medical history, physical examination, 12-lead ECG, blood chemistry profile, hematology, urinalysis and in the opinion of the Principal Investigator.
7. Female participants, if of child-bearing potential and sexually active, and male participants, if sexually active with a partner of child-bearing potential, who agree to use a medically acceptable and effective birth control method throughout the study and for one week following the end of the study. Medically acceptable methods of contraception that may be used by the participant and/or his/her partner include abstinence, birth control pills or patches, diaphragm with spermicide, intrauterine device (IUD), condom with foam or spermicide, vaginal spermicidal suppository, surgical sterilization and progestin implant or injection. Prohibited methods include: the rhythm method, withdrawal, condoms alone, or diaphragm alone.

Exclusion Criteria:

1. Patients with agitation caused by acute intoxication must be excluded. Positive identification of non-prescription drugs during urine screening excludes the subject.
2. Patients treated with benzodiazepines or other hypnotics or oral or short-acting intramuscular antipsychotics within 4 hours prior to study drug administration must be excluded.
3. Patients treated with injectable depot neuroleptics within one dose interval prior to study drug administration must be excluded.
4. Patients with a history of allergic reactions to loxapine or amoxapine must be excluded.
5. Female patients who have a positive pregnancy test at screening or are breastfeeding must be excluded.
6. Patients who have Parkinson's disease, hydrocephalus, seizure disorder, or history of significant head trauma must be excluded.
7. Patients with laboratory or ECG abnormalities considered clinically significant by the investigator or qualified designee that would have clinical implications for the patient's participation in the study must be excluded.
8. Patients with serious and unstable illnesses including current hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease and congestive heart failure), endocrinologic, neurologic (including stroke, transient ischemic attack, subarachnoidal bleeding, brain tumor, encephalopathy, and meningitis), or hematologic disease must be excluded.
9. Patients who have a history of acute or chronic pulmonary disease that precludes administration of Staccato Loxapine (asthma, bronchitis, emphysema) must be excluded.
10. Patients who have received an investigational drug within 30 days prior to the current agitation episode must be excluded.
11. Patients who are considered by the investigator, for any reason, to be an unsuitable candidate for receiving loxapine, or unable to use the inhalation device, must be excluded.