Staccato Loxapine in Agitation (Proof of Concept)
Condition: Schizophrenia
MeSH terms: Psychomotor Agitation; Schizophrenia
Intervention: Inhaled Placebo; Inhaled Loxapine 5 mg; Inhaled Loxapine 10 mg
Intervention description: Inhaled Placebo, single dose; Inhaled Staccato Loxapine 5 mg, single dose; Inhaled Staccato Loxapine 10 mg, single dose
Intervention MeSH terms: Loxapine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 129.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Agitation; Schizophrenia

Summary:

      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.
    

Eligibility criteria:

        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.