Conditions: Healthy Volunteers
Keywords: ADASUVE inhaled loxapine drug drug interaction lorazepam acute treatment of agitation
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 22
Healthy volunteers: yes

Brief summary:
This study will compare the safety and effects over time for giving both ADASUVE and lorazepam (intramuscular) compared to that of each agent given alone.

Detailed description:
The objective of this study is to compare the safety and pharmacodynamic profiles of concomitant administration of a single dose of ADASUVE and lorazepam (IM) compared to that of each agent administered alone. Respiratory pharmacodynamics will be monitored through recordings of respirations/minute and pulse oximetry. Other pharmacodynamic safety measures will include effects on blood pressure, heart rate, sedation and psychomotor measures of attention, information processing speed, reaction time, and coordination.

Initially, 4 subjects will receive lorazepam 1 mg IM + ADASUVE 10 mg open label to validate the dose regimen. After the safety data are reviewed and the dose regimen confirmed, 18 non-obese, healthy male or female volunteers between the ages of 18 and 50 will be enrolled in this double-blinded, double-dummy, randomized, 3-period cross-over drug interaction study.

Arms:
arm 1: Inhaled Staccato loxapine 10 mg + IM lorazepam 1 mg to confirm tolerability of combined treatment arm 2: Treatment: A = Lorazepam 1 mg IM + inhaled placebo, B = Lorazepam 1 mg IM + inhaled loxapine 10 mg, C= Placebo IM + inhaled loxapine 10 mg arm 3: Treatment: A = Lorazepam 1 mg IM + inhaled placebo, B = Lorazepam 1 mg IM + inhaled loxapine 10 mg, C= Placebo IM + inhaled loxapine 10 mg arm 4: Treatment: A = Lorazepam 1 mg IM + inhaled placebo, B = Lorazepam 1 mg IM + inhaled loxapine 10 mg, C= Placebo IM + inhaled loxapine 10 mg arm 5: Treatment: A = Lorazepam 1 mg IM + inhaled placebo, B = Lorazepam 1 mg IM + inhaled loxapine 10 mg, C= Placebo IM + inhaled loxapine 10 mg arm 6: Treatment: A = Lorazepam 1 mg IM + inhaled placebo, B = Lorazepam 1 mg IM + inhaled loxapine 10 mg, C= Placebo IM + inhaled loxapine 10 mg arm 7: Treatment: A = Lorazepam 1 mg IM + inhaled placebo, B = Lorazepam 1 mg IM + inhaled loxapine 10 mg, C= Placebo IM + inhaled loxapine 10 mg

Interventions: intervention 1: Lorazepam 1 mg IM intervention 2: Inhaled loxapine 10 mg intervention 3: Inhaled Placebo intervention 4: Placebo IM
Intervention descriptions: intervention 1: Lorazepam 1 mg intramuscular intervention 2: Inhaled Staccato loxapine 10 mg intervention 3: Inhaler with no drug in it to mimic the ADASUVE inhaler intervention 4: intramuscular placebo to mimic lorazepam 1 mg IM

Protocol document: