ADASUVE-Lorazepam Drug-Drug Interaction
Condition: Healthy Volunteers
Intervention: Lorazepam 1 mg IM; Inhaled loxapine 10 mg; Inhaled Placebo; Placebo IM
Intervention description: Lorazepam 1 mg intramuscular; Inhaled Staccato loxapine 10 mg; Inhaler with no drug in it to mimic the ADASUVE inhaler; intramuscular placebo to mimic lorazepam 1 mg IM
Intervention MeSH terms: Lorazepam; Loxapine
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: ADASUVE; inhaled loxapine; drug drug interaction; lorazepam; acute treatment of agitation

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.
    

Eligibility criteria:

        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.