Staccato Loxapine in Agitation (Proof of Concept)

Study Overview
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Brief Summary
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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.

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

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Inhaled Placebo
* Drug: Inhaled Loxapine 5 mg
* Drug: Inhaled Loxapine 10 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients between the ages of 18 to 65 years, inclusive. Patients who have met DSM-IV criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder. 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). Patients who have a value of ≥ 4 (out of 7) on at least 1 of the 5 items on the PANSS Excited Component. Patients who read and understand English and provide written informed consent. 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. 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: Patients with agitation caused by acute intoxication must be excluded. Positive identification of non-prescription drugs during urine screening excludes the subject. 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. Patients treated with injectable depot neuroleptics within one dose interval prior to study drug administration must be excluded. Patients with a history of allergic reactions to loxapine or amoxapine must be excluded. Female patients who have a positive pregnancy test at screening or are breastfeeding must be excluded. Patients who have Parkinson's disease, hydrocephalus, seizure disorder, or history of significant head trauma must be excluded. 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. 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. Patients who have a history of acute or chronic pulmonary disease that precludes administration of Staccato Loxapine (asthma, bronchitis, emphysema) must be excluded. Patients who have received an investigational drug within 30 days prior to the current agitation episode must be excluded. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Inhaled Placebo<br>Inhaled Staccato Placebo, single dose | Drug: Inhaled Placebo<br>* Inhaled Placebo, single dose<br>* Other names: Staccato Loxapine Placebo;|
| Experimental: Inhaled Loxapine 5 mg<br>Inhaled Staccato Loxapine 5 mg, single dose | Drug: Inhaled Loxapine 5 mg<br>* Inhaled Staccato Loxapine 5 mg, single dose<br>* Other names: ADASUVE 5 mg;|
| Experimental: Inhaled Loxapine 10 mg<br>Inhaled Staccato Loxapine 10 mg, single dose | Drug: Inhaled Loxapine 10 mg<br>* Inhaled Staccato Loxapine 10 mg, single dose<br>* Other names: ADASUVE 10 mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PANSS-EC Change From Baseline | The Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) comprises 5 items associated with agitation: poor impulse control, tension, hostility, uncooperativeness, and excitement; each scored 1 (min) to 7 (max). The PANSS-EC, the sum of these 5 subscales, thus ranges from 5 to 35. Individuals were eligible if they had a PANSS-EC of ≥14 (out of 35) and a score ≥4 (out of 7) on at least 1 of the 5 items. | 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BARS Change From Baseline After Drug Treatment | Change from baseline on the Behavioral Activity Rating Scale (BARS) ranging from 1 to 7 where: 1 = difficult or unable to rouse, 2 = asleep but responds normally to verbal or physical contact, 3 = drowsy, appears sedated, 4 = quiet, and awake (normal level of activity), 5 = signs of overt (physical or verbal) activity, calms down with instructions, 6 = extremely or continuously active, not requiring restraint, 7 = violent, requires restraint. | 2 hours | 
| Clinical Global Impressions-Improvement Scale (CGI-I) After Drug Administration | Clinical Global Impression- Improvement (CGI-I) scores ranged from 1 to 7: 0=not assessed (missing), 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, 7=very much worse. | 2 hours | 
| CGI-I Responders | Frequency of response based on the CGI-I (defined as achieving a CGI-I score of 1 or 2 at 2 hours after administration of the inhalation) | 2 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Agitation, Schizophrenia