Clinical trial NCT00555412: Staccato Loxapine Multidose PK
Official title: Safety, Tolerability, and Pharmacokinetics of Multiple Doses of Staccato® Loxapine for Inhalation in Subjects on Chronic, Stable Antipsychotic Regimens
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Volunteers on Chronic, Stable Antipsychotic Regimens
Keywords: pharmacokinetic
multidose
Staccato Loxapine
Lead sponsor: Alexza Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Atlanta Center for Medical Research
First posted: 2007-11-08
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility 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.

Primary outcomes:
measure: PK parameters: tmax, Cmax, AUClast, AUCinf, ke, t1/2 and clearance will be estimated for each subject and for the population using noncompartmental methods.
timeFrame: 48 hours
Secondary outcomes:
measure: Plasma concentration-time (PK) profiles will be produced for each subject and a mean PK profile for subjects completing for each dose group
timeFrame: 24 hours
measure: Tolerability will be assessed based on treatment emergent adverse events, vital signs, ECG and a visual-analog sedation scale.
timeFrame: 24 hours
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research
state: Georgia
Study officials:
affiliation: Atlanta Center for Medical Research
name: Robert Riesenberg, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.