Staccato Loxapine Multidose PK

Safety, Tolerability, and Pharmacokinetics of Multiple Doses of Staccato® Loxapine for Inhalation in Subjects on Chronic, Stable Antipsychotic Regimens

The objectives of this trial are to assess the safety, tolerability, and pharmacokinetics of multiple inhaled doses of Staccato Loxapine.

Study Overview

• Status: Completed
• Conditions: Volunteers on Chronic, Stable Antipsychotic Regimens
• Intervention / Treatment: Drug: A - 10 mg loxapine q 4 h x 3 (30 mg total); Drug: B - 10 mg x 1, 5 mg x 2 loxapine q 4 h (20 mg total); Drug: C - 5 mg loxapine q 4 h x 3 (15 mg total); Drug: D - inhaled placebo q 4 h x 3

Detailed Description

The purpose of the present Phase 1 study in schizophrenic patients is to assess the safety and pharmacokinetics of multiple doses of Staccato Loxapine given within a 24 hour time period. The study will be conducted in schizophrenic patients who are on chronic, stable antipsychotic medication. Patients meeting entry criteria will be randomized to one of three dose sequences of Staccato Loxapine or to Staccato Placebo. Following administration of medications, safety, tolerability and pharmacokinetic assessments will be conducted at serial time points.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

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 include:

1. Male and female subjects between the ages of 18 to 65 years, inclusive.
2. Subjects who are on stable, oral, chronic (>2 mos) antipsychotic medication regimen and who are able to tolerate the rapid oral dose taper and substitution regimen.

Exclusion Criteria include:

1. Subjects who are currently treated with injectable depot neuroleptics within one dose interval must be excluded.
2. Subjects who have received loxapine or amoxapine within the last 30 days must be excluded.
3. Subjects with a history of allergy or intolerance to dibenzoxazepines (loxapine and amoxapine) must be excluded.
4. Subjects with a history of movement disorders including Parkinson's disease or a history of neuroleptic malignant syndrome must be excluded.
5. Subjects who have a history within the past year of drug or alcohol dependence or abuse as defined by DSM-4 must be excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: A - 10 mg loxapine q 4 h x 3 (30 mg total)	Drug: A - 10 mg loxapine q 4 h x 3 (30 mg total); loxapine aerosol inhalation high dose regimen (30 mg total); Other Names: Staccato Loxapine 10 mg
EXPERIMENTAL: B - 10 mg x 1, 5 mg x 2 loxapine q 4 h (20 mg total)	Drug: B - 10 mg x 1, 5 mg x 2 loxapine q 4 h (20 mg total); loxapine aerosol inhalation middle dose regimen (20 mg total); Other Names: Staccato Loxapine 5 and 10 mg
EXPERIMENTAL: C - 5 mg loxapine q 4 h x 3 (15 mg total)	Drug: C - 5 mg loxapine q 4 h x 3 (15 mg total); loxapine aerosol inhalation low dose regimen (15 mg total); Other Names: Staccato Loxapine 5 mg
PLACEBO_COMPARATOR: D - inhaled placebo q 4 h x 3	Drug: D - inhaled placebo q 4 h x 3; placebo aerosol inhalation (0 mg total); Other Names: Staccato Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
PK parameters: tmax, Cmax, AUClast, AUCinf, ke, t1/2 and clearance will be estimated for each subject and for the population using noncompartmental methods.	48 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma concentration-time (PK) profiles will be produced for each subject and a mean PK profile for subjects completing for each dose group	24 hours
Tolerability will be assessed based on treatment emergent adverse events, vital signs, ECG and a visual-analog sedation scale.	24 hours

Collaborators and Investigators

• Sponsor: Alexza Pharmaceuticals, Inc.
• Collaborators: Atlanta Center for Medical Research

Publications and helpful links

General Publications

• Spyker DA, Riesenberg RA, Cassella JV. Multiple dose pharmacokinetics of inhaled loxapine in subjects on chronic, stable antipsychotic regimens. J Clin Pharmacol. 2015 Sep;55(9):985-94. doi: 10.1002/jcph.502. Epub 2015 May 6.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (ACTUAL): December 1, 2007
• Study Completion (ACTUAL): December 1, 2007

Study Registration Dates

• First Submitted: November 6, 2007
• First Submitted That Met QC Criteria: November 6, 2007
• First Posted (ESTIMATE): November 8, 2007

Study Record Updates

• Last Update Posted (ACTUAL): March 15, 2017
• Last Update Submitted That Met QC Criteria: March 13, 2017
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: pharmacokinetic; multidose; Staccato Loxapine
• Additional Relevant MeSH Terms: 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-004-102

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