Staccato Loxapine Multidose PK

Alexza Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Volunteers on Chronic, Stable Antipsychotic Regimens

Treatments: Drug: B - 10 mg x 1, 5 mg x 2 loxapine q 4 h (20 mg total); Drug: A - 10 mg loxapine q 4 h x 3 (30 mg total); Drug: D - inhaled placebo q 4 h x 3; Drug: C - 5 mg loxapine q 4 h x 3 (15 mg total)

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT00555412

AMDC-004-102

Details and patient eligibility

About

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

Full 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.

Enrollment: 40 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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40 participants in 4 patient groups, including a placebo group

A - 10 mg loxapine q 4 h x 3 (30 mg total)

Experimental group

Treatment:

Drug: A - 10 mg loxapine q 4 h x 3 (30 mg total)

B - 10 mg x 1, 5 mg x 2 loxapine q 4 h (20 mg total)

Experimental group

Treatment:

Drug: B - 10 mg x 1, 5 mg x 2 loxapine q 4 h (20 mg total)

C - 5 mg loxapine q 4 h x 3 (15 mg total)

Experimental group

Treatment:

Drug: C - 5 mg loxapine q 4 h x 3 (15 mg total)

D - inhaled placebo q 4 h x 3

Placebo Comparator group

Treatment:

Drug: D - inhaled placebo q 4 h x 3