Staccato Loxapine Multidose PK

Condition(s) targeted: Volunteers on Chronic, Stable Antipsychotic Regimens

Intervention: 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 (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: Alexza Pharmaceuticals, Inc.

Official(s) and/or principal investigator(s):
Robert Riesenberg, MD, Principal Investigator, Affiliation: Atlanta Center for Medical Research

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

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

Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: PK parameters: tmax, Cmax, AUClast, AUCinf, ke, t1/2 and clearance will be estimated for each subject and for the population using noncompartmental methods.

Secondary outcome:

Plasma concentration-time (PK) profiles will be produced for each subject and a mean PK profile for subjects completing for each dose group

Tolerability will be assessed based on treatment emergent adverse events, vital signs, ECG and a visual-analog sedation scale.

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.

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

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.

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

Starting date: October 2007
Last updated: June 24, 2013