Staccato Loxapine in Agitated Patients With Schizophrenia

A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Multi-Dose Efficacy and Safety Study of Staccato® Loxapine for Inhalation in Schizophrenic Patients With Agitation

Phase 3 safety and efficacy study of Staccato Loxapine in the treatment of acute agitation in schizophrenic patients

Study Overview

• Status: Completed
• Conditions: Patients With Schizophrenia and Acute Agitation
• Intervention / Treatment: Drug: Inhaled loxapine 5 mg; Drug: Inhaled loxapine 10 mg; Drug: Inhaled placebo

Detailed Description

This is an in-clinic, multi-center, randomized, double-blind, placebo-controlled study of 2 dose levels of Staccato Loxapine, 5 and 10 mg. Patients may receive up to 3 doses of study drug in a 24-hour period, depending on their clinical status. The primary endpoint is the change from baseline in the PANSS (Positive and Negative Symptom Scale) Excited Component (also known as PEC) score, performed at 2 hours after the first dose.

• Study Type: Interventional
• Enrollment (Actual): 344
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Atlanta Center for Medical Research

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:

• Male and female adult patients with schizophrenia and acute agitation

Exclusion Criteria:

• Agitation caused primarily by acute intoxication
• History of drug or alcohol dependence
• Treatment with benzodiazepines or other hypnotics within 4 hours prior to study drug administration

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
Experimental: Inhaled Loxapine 5 mg; Inhaled Loxapine 5 mg, may repeat x 1 or 2 after 2 hours	Drug: Inhaled loxapine 5 mg; Inhaled loxapine 5 mg; Other Names: ADASUVE
Experimental: Inhaled Loxapine 10 mg; Inhaled Loxapine 10 mg, may repeat x 1 or 2 after 2 hours	Drug: Inhaled loxapine 10 mg; Inhaled loxapine 10 mg; Other Names: ADASUVE
Placebo Comparator: Inhaled placebo; Inhaled Loxapine placebo, may repeat x 1 or 2 after 2 hours	Drug: Inhaled placebo; Inhaled placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in PANSS-EC 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.	Baseline and 2 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Baseline and 2 hours
Clinical Global Impression-Improvement (CGI-I) Score	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.	Baseline and 2 hours

Collaborators and Investigators

• Sponsor: Alexza Pharmaceuticals, Inc.
• Investigators: Study Director: Robert S Fishman, MD, Alexza Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• Zeller S, Zun L, Cassella JV, Spyker DA, Yeung PP. Response to inhaled loxapine in patients with schizophrenia or bipolar I disorder: PANSS-EC responder analyses. BJPsych Open. 2017 Nov 10;3(6):285-290. doi: 10.1192/bjpo.bp.117.005363. eCollection 2017 Nov.
• Lesem MD, Tran-Johnson TK, Riesenberg RA, Feifel D, Allen MH, Fishman R, Spyker DA, Kehne JH, Cassella JV. Rapid acute treatment of agitation in individuals with schizophrenia: multicentre, randomised, placebo-controlled study of inhaled loxapine. Br J Psychiatry. 2011 Jan;198(1):51-8. doi: 10.1192/bjp.bp.110.081513.

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): May 1, 2008

Study Registration Dates

• First Submitted: February 25, 2008
• First Submitted That Met QC Criteria: February 25, 2008
• First Posted (Estimate): March 5, 2008

Study Record Updates

• Last Update Posted (Actual): July 26, 2017
• Last Update Submitted That Met QC Criteria: June 28, 2017
• Last Verified: June 1, 2008

More Information

Terms related to this study

• Keywords: schizophrenia, agitation, inhaled loxapine, ADASUVE
• 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-004-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• 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