ADASUVE-Lorazepam Drug-Drug Interaction

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.

Inclusion Criteria:

- Male and female subjects between the ages of 18 to 50 years, inclusive.

- Body mass index (BMI) ≥18 and ≤32.

- Subjects who are willing and able to comply with the study schedule and requirements,
and stay at the CRU for 9 days.

- Subjects who speak, read, and understand English and are willing and able to provide
written informed consent on an IRB approved form prior to the initiation of any study
procedures.

- Subjects who are in good general health prior to study participation as determined by
a detailed medical history, physical examination, 12-lead ECG, blood chemistry
profile, hematology, urinalysis, and in the opinion of the Principal Investigator.

- Female participants (if of child-bearing potential and sexually active) who agree to
use a medically acceptable and effective birth control method throughout the study and
for 30 days following the end of the study

- Male participants (if sexually active with a partner of child-bearing potential) who
agree to use a medically acceptable and effective birth control method from the first
dose and for 90 days following last dose of study drug. Male participants must refrain
from donating sperm for the same period.

Exclusion Criteria:

- Subject history, which includes: any cardiovascular disease or disorder; asthma,
chronic obstructive lung disease, or any use of an inhaler prescribed for wheezing or
bronchospasm must be excluded; sleep apnea; acute narrow-angle glaucoma; any
neurological, gastrointestinal, hepatic, renal, hematologic, endocrine and/or
metabolic disease or disorder; psychiatric illness or mental disorder except for short
term situational anxiety or depression of < 2 years duration; any substance abuse or
addiction within the last 2 years; pregnancy within the past 6 months.

- Subjects who have taken prescription or nonprescription medication within 7 days of
Visit 2.

- Subjects who have had an acute illness within the last 7 days of Visit 2.

- Subjects who have a history of HIV positivity.

- Subjects who test positive for alcohol or have a positive urine drug screen.

- Subjects who have a history of allergy or intolerance to loxapine or amoxapine.

- Subjects who have a history of allergy or intolerance to lorazepam or any other
benzodiazepine.

- Subjects who have a history of allergy or intolerance to polyethylene glycol,
propylene glycol, or benzyl alcohol

- Female subjects who have a positive pregnancy test at screening or at admission to
Visit 2, or are breastfeeding.

- Subjects who have received an investigational drug within 30 days prior to the
Screening Visit.

- Subjects who have any other disease(s), by history, physical examination, or
laboratory abnormalities that, in the investigator's opinion, presents undue risk to
the subject or may confound the interpretation of study results.

- Subjects who are considered by the investigator, for any reason, to be an unsuitable
candidate for receiving lorazepam or ADASUVE.