Staccato Prochlorperazine Thorough QT/QTc Study

Condition(s) targeted: Migraine

Intervention: Prochlorperazine (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: Alexza Pharmaceuticals, Inc.

Official(s) and/or principal investigator(s):
Randall R Stoltz, MD, Principal Investigator, Affiliation: Covance GFI Research, Evansville, IN 47714

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

Official title: Thorough QT/QTc Study of Staccato® Prochlorperazine for Inhalation in Healthy Volunteers

Study design: Screening, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Crossover Assignment, Safety Study

Primary outcome: Time-matched differences in changes from baseline for each treatment vs. placebo QTc

Secondary outcome: Categorical analysis of incidence of numbers and percents of subjects with absolute values and changes from baseline

Detailed description: The planned study is a single dose, double-blind, double-dummy, active and placebo controlled, randomized, 4-period cross-over study investigating investigating 2 doses levels of Staccato Prochlorperazine, a positive control with known QT/QTc prolongation (oral moxifloxacin), and placebo.

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

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.

Covance Clinical Research Unit Inc., Evansville, Indiana 47714, United States

Starting date: October 2007
Ending date: December 2007
Last updated: January 7, 2008