Staccato Loxapine Single Dose PK
Condition: Schizophrenia
MeSH terms: Schizophrenia
Intervention: inhaled Loxapine 0.625 mg; inhaled Loxapine 1.25 mg; inhaled Loxapine 2.5 mg; inhaled Loxapine 5 mg; inhaled Loxapine 10 mg; inhaled Placebo (0 mg)
Intervention description: Single 0.625 mg (lowest) dose of inhaled loxapine; Single 1.25 mg (2nd) dose of inhaled loxapine; Single 2.5 mg (3rd) dose of inhaled loxapine; Single 5 mg (4th) dose of inhaled loxapine; Single 10 mg (5th) dose of inhaled loxapine; Single placebo dose of inhaled loxapine
Intervention MeSH terms: Loxapine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Schizophrenia, Staccato Loxapine

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male and female subjects between the ages of 18 to 55 years, inclusive.

          2. Subjects with a body mass index (BMI) ≥21 and ≤30.

          3. 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.

          4. Subjects who are willing and able to be confined to the Clinical Research Unit (CRU)
             for approximately 2 days and comply with the study schedule and study requirements.

          5. Subjects who are in good general health as determined by a complete medical history,
             physical examination, 12-lead ECG, spirometry, blood chemistry profile, hematology,
             and urinalysis.

        Exclusion Criteria:

          1. Subjects who regularly consume large amounts of xanthine-containing substances (i.e.,
             more than 5 cups of coffee or equivalent amounts of xanthine-containing substances per
             day).

          2. Subjects who have taken prescription or nonprescription medication (with the exception
             of vitamins and acetaminophen if medically necessary) within 5 days of Visit 2
             (Baseline).

          3. Subjects who have had an acute illness within 5 days of Visit 2 (Baseline).

          4. Subjects who have received an investigational drug within 30 days (or within 5 half
             lives of the investigational drug, if >30 days) prior to Visit 2 (Baseline).

          5. Subjects who have smoked tobacco within the last year.

          6. Subjects who have a history within the past 2 years of drug or alcohol dependence or
             abuse as defined by DSM-4.

          7. Subjects with a history of HIV positivity.

          8. Subjects with a history of allergy or intolerance to dibenzoxazepines (amoxapine and
             loxapine).

          9. Subjects with a known history of contraindications to anticholinergics (bowel
             obstructions, urinary retention, acute glaucoma).

         10. Subjects with a history of pheochromocytoma, seizure disorder, Parkinson's disease, or
             Restless Leg Syndrome (RLS).

         11. Subjects who test positive for alcohol or have a positive urine drug screen at Visit 1
             or Visit 2.

         12. Subjects who have hypotension (systolic blood pressure ≤90 mmHg, diastolic blood
             pressure ≤50 mmHg), or hypertension (systolic blood pressure ≥140 mmHg, diastolic
             blood pressure ≥90 mmHg).

         13. Subjects who have a clinically significant ECG abnormality.

         14. Subjects with a history of unstable angina, syncope, coronary artery disease,
             myocardial infarction, congestive heart failure (CHF), stroke, transient ischemic
             attack (TIA), or a neurological disorder.

         15. Subjects who have a history of pulmonary disease that precludes administration of
             Staccato Loxapine (asthma, bronchitis, bronchospasm, emphysema).

         16. Subjects who have an FEV1 less than 80% of predicted values on spirometry assessments
             at Visit 1.

         17. Female subjects who are breastfeeding or have a positive pregnancy test at Visit 1 or
             Visit 2.

         18. Female participants of child-bearing potential or within 1 year of menopause, and
             sexually active are excluded unless they use a medically acceptable and effective
             birth control method throughout the study and for 1 week following the end of the
             study. Medically acceptable methods of contraception include abstinence, diaphragm
             with spermicide, intrauterine device (IUD), condom with foam or spermicide, vaginal
             spermicidal suppository, surgical sterilization, and birth control pills. Unacceptable
             methods include: the rhythm method, withdrawal, condoms alone, or diaphragm alone.

         19. Subjects who have any other disease or condition, by history, physical examination, or
             laboratory abnormalities that in the investigator's opinion, would present undue risk
             to the subject, or may confound the interpretation of study results.