Staccato Prochlorperazine Thorough QT/QTc
Condition: Cardiotoxicity
MeSH terms: Cardiotoxicity
Intervention: Inhaled placebo; Oral placebo; Inhaled prochlorperazine 5 mg; Inhaled prochlorperazine 10 mg; Oral moxifloxacin
Intervention description: Inhaled Staccato placebo (0 mg); Oral placebo (identical to 400 mg moxifloxacin); Staccato prochlorperazine 5 mg, single dose; Inhaled prochlorperazine 10 mg, single dose; Oral moxifloxacin 400 mg, si/ngle dose
Intervention MeSH terms: Moxifloxacin; Prochlorperazine; Loxapine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Female and male subjects in approximately equal numbers were randomly assigned (1:1:1:1) to receive the 4 treatment sequences
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: This was a double-blind, double dummy, placebo controlled, randomized 4-period crossover study to assess the effects of single doses of 5 and 10 mg of Staccato Prochlorperazine on QT intervals.
Enrollment: 48.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Inhaled prochlorperazine, Thorough Qt/QTc,

Summary:

      To assess the safety of Staccato Prochlorperazine on cardiac repolarization (QTc interval
      duration) at 2 dose levels compared to placebo in healthy volunteers.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male and female subjects between the ages of 18 to 65 years, inclusive.

          2. Body mass index (BMI) ≥21 and ≤30.

          3. Subjects who are willing and able to comply with the study schedule and requirements,
             and stay at the CRU for a 3-day period and 3 consecutive 2-day periods.

          4. 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.

          5. 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.

          6. Female participants (if of child-bearing potential and sexually active) and male
             participants (if sexually active with a partner of child-bearing potential) who agree
             to use a medically acceptable and effective birth control method throughout the study
             and for one week following the end of the study.

        Exclusion Criteria:

          1. Subjects who regularly consume large amounts of xanthine-containing substances must be
             excluded.

          2. Subjects who have taken prescription or nonprescription medication within 5 days of
             Treatment Period 1 must be excluded.

          3. Subjects who have had an acute illness within the last 5 days of Treatment Period 1
             must be excluded.

          4. Subjects who have smoked tobacco within the last year must be excluded.

          5. Subjects who have a history of HIV positivity must be excluded.

          6. Subjects who have a history of allergy or intolerance to prochlorperazine or
             phenothiazines must be excluded.

          7. Subjects who have a history of contraindication to anticholinergics must be excluded.

          8. Subjects who have a history of pheochromocytoma, seizure disorder, Parkinson's
             disease, or Restless Leg Syndrome must be excluded.

          9. Subjects who have an ECG abnormality must be excluded.

         10. Subjects who have a history within the past 2 years of drug or alcohol dependence or
             abuse as defined by DSM-4 must be excluded.

         11. Subjects who have a history of syncope, unstable angina, myocardial infarction (within
             6 months), congestive heart failure, transient ischemic attack, or pheochromocytoma
             must be excluded.

         12. Subjects who have a history of asthma or chronic obstructive lung disease must be
             excluded.

         13. Subjects who have hypotension (systolic ≤90 mmHg, diastolic ≤50 mmHg), or hypertension
             (systolic ≥140 mmHg, diastolic blood pressure ≥90 mmHg) must be excluded.

         14. Subjects who test positive for alcohol or have a positive urine drug screen must be
             excluded.

         15. Female subjects who have a positive pregnancy test at screening or during
             randomization visit, or are breastfeeding must be excluded.

         16. Subjects who have received an investigational drug within 30 days prior to the
             Screening Visit must be excluded.

         17. Subjects who are considered by the investigator, for any reason, to be an unsuitable
             candidate for receiving prochlorperazine, or unable to use the inhalation device, must
             be excluded.

         18. Subjects who have any other disease(s), by history, physical examination, or
             laboratory abnormalities (ALT or AST > 2-fold the upper limit of normal, bilirubin >
             1.5 mg/dL, or creatinine > 1.8 mg/dL) or that in the investigator's opinion present
             undue risk to the subject or may confound the interpretation of study results must be
             excluded.