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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Inhaled Placebo; Drug: Inhaled Loxapine 5 mg; Drug: Inhaled Loxapine 10 mg

• Study Type: Interventional
• Enrollment (Actual): 129
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Upland, California, United States, 91786
      • Pacific Clinical Research Medical Group, 1317 West Foothill Blvd, Suite 200,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Inhaled Placebo; Inhaled Staccato Placebo, single dose	Drug: Inhaled Placebo; Inhaled Placebo, single dose; Other Names: Staccato Loxapine Placebo
Experimental: Inhaled Loxapine 5 mg; Inhaled Staccato Loxapine 5 mg, single dose	Drug: Inhaled Loxapine 5 mg; Inhaled Staccato Loxapine 5 mg, single dose; Other Names: ADASUVE 5 mg; Inhaled Staccato Loxapine 5 mg
Experimental: Inhaled Loxapine 10 mg; Inhaled Staccato Loxapine 10 mg, single dose	Drug: Inhaled Loxapine 10 mg; Inhaled Staccato Loxapine 10 mg, single dose; Other Names: ADASUVE 10 mg; Inhaled Staccato Loxapine 10 mg

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Alexza Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Daniel Zimbroff, MD, Pacific Clinical Research Medical Group

Publications and helpful links

General Publications

• Allen MH, Feifel D, Lesem MD, Zimbroff DL, Ross R, Munzar P, Spyker DA, Cassella JV. Efficacy and safety of loxapine for inhalation in the treatment of agitation in patients with schizophrenia: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2011 Oct;72(10):1313-21. doi: 10.4088/JCP.10m06011yel.

Study record dates

Study Major Dates

• Study Start: August 1, 2006
• Primary Completion (Actual): January 1, 2007
• Study Completion (Actual): January 1, 2007

Study Registration Dates

• First Submitted: August 25, 2006
• First Submitted That Met QC Criteria: August 25, 2006
• First Posted (Estimate): August 29, 2006

Study Record Updates

• Last Update Posted (Actual): January 2, 2018
• Last Update Submitted That Met QC Criteria: May 30, 2017
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: Schizophrenia; Agitation
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Schizophrenia Spectrum and Other Psychotic Disorders; Dyskinesias; Psychomotor Disorders; Schizophrenia; Psychomotor Agitation; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Dopamine Agents; Dopamine Antagonists; Loxapine
• Other Study ID Numbers: AMDC-004-201; 004-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD submitted to regulatory authorities. Others may contact Alexza Pharmaceuticals, Inc. Please send your request to ClinicalTrialsInfo@alexza.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No