Conditions: Schizophrenia
Keywords: Schizophrenia, Staccato Loxapine
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 50
Healthy volunteers: yes

Brief summary:
The objective of this study was to assess the safety, tolerability and pharmacokinetics of a single inhaled dose of (administered in 1 or 2 puffs) Staccato Loxapine in healthy volunteers.

Detailed description:
Safety and pharmacokinetic data obtained from 50 subjects (between the ages of 18 to 55 years) entered into this randomized, placebo-controlled study. To obtain 50 enrolled subjects, screening procedures and inclusion/exclusion criteria were evaluated for 126 subjects during a variable screening period of up to 21 days. Once enrolled, subjects were randomized to either Staccato Loxapine or Staccato placebo.

Plasma samples for pharmacokinetic analysis were collected beginning on Day 0, pre-dose and continuing for 24 hr post dose. Blood samples for the PK analysis of loxapine and its metabolites (8-OH loxapine, 7-OH loxapine and amoxapine) were obtained at time 0 (immediately before dosing), at 30 sec, 1, 2, 3, 5, 10, 30, 45 min, 1, 2, 4, 6, 12, 24 hr after dosing. Plasma concentrations of loxapine and metabolites were used to estimate the following PK parameters for loxapine and its metabolites: area under the plasma concentration time curve from time 0 extrapolated to infinity (AUCinf), AUC from time 0 to time tlast, the last quantifiable concentration (AUClast), maximum observed plasma concentration (Cmax), observed time of Cmax (tmax), terminal phase elimination rate constant (ke), apparent terminal elimination half life calculated from ke (T½ ), apparent total body clearance / fraction absorbed calculated from AUCinf and dose (CL/F) (for loxapine and the metabolites where permitted by measurable concentrations).

Safety was evaluated by the incidence of adverse events, clinical laboratory testing (blood chemistry, hematology, and urinalysis), physical examination, vital signs, pulse oximetry, postural vital signs, 12-lead electrocardiogram, pulmonary function tests, continuous 12-lead Holter monitoring, sedation assessments, akathisia assessments.

Arms:
arm 1: Single 0.625 mg dose of inhaled loxapine or Single Placebo dose of inhaled loxapine arm 2: Single 1.25 mg dose of inhaled loxapine or Single Placebo dose of inhaled loxapine arm 3: Single 2.5 mg dose of inhaled loxapine or Single Placebo dose of inhaled loxapine arm 4: Single 5 mg dose of inhaled loxapine or Single Placebo dose of inhaled loxapine arm 5: Single 10 mg dose of inhaled loxapine or Single Placebo dose of inhaled loxapine

Interventions: intervention 1: inhaled Loxapine 0.625 mg intervention 2: inhaled Loxapine 1.25 mg intervention 3: inhaled Loxapine 2.5 mg intervention 4: inhaled Loxapine 5 mg intervention 5: inhaled Loxapine 10 mg intervention 6: inhaled Placebo (0 mg)
Intervention descriptions: intervention 1: Single 0.625 mg (lowest) dose of inhaled loxapine intervention 2: Single 1.25 mg (2nd) dose of inhaled loxapine intervention 3: Single 2.5 mg (3rd) dose of inhaled loxapine intervention 4: Single 5 mg (4th) dose of inhaled loxapine intervention 5: Single 10 mg (5th) dose of inhaled loxapine intervention 6: Single placebo dose of inhaled loxapine

Protocol document: