Clinical trial NCT00543062: Staccato Prochlorperazine Thorough QT/QTc
Official title: Thorough QT/QTc Study of Staccato® Prochlorperazine for Inhalation in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cardiotoxicity
Keywords: Inhaled prochlorperazine, Thorough Qt/QTc,
Lead sponsor: Alexza Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2007-10-12
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Female and male subjects in approximately equal numbers were randomly assigned (1:1:1:1) to receive the 4 treatment sequences
Primary purpose: TREATMENT

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

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.

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.

Primary outcomes:
measure: Maximum Effect of Inhaled Prochlorperazine on Cardiac Repolarization (QTc Interval Duration) at the Maximum Clinical Dose Compared to Placebo
timeFrame: 1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hr
Secondary outcomes:
measure: QTcI Versus Prochlorperazine Concentration
timeFrame: 1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hr
measure: Numbers and % of Subjects With QTcI > 450 ms
timeFrame: 24 hours
measure: Numbers and % of Subjects With QTcI > 480 ms
timeFrame: 1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hr
measure: Numbers and % of Subjects With QTcI Change > 30 ms
timeFrame: 1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hr
measure: Numbers and % of Subjects With QTcI Change > 60 ms
timeFrame: 1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hr
Other outcomes:
measure: Maximum Effect of Moxifloxacin on Cardiac Repolarization (QTc Interval Duration) Compared to Placebo (Study Assay Sensitivity)
timeFrame: 1, 1.5, 2, 2.5, 3, 5 hours
Locations:
city: Evansville
country: United States
facility: Covance Clinical Research Unit Inc.
state: Indiana
Study officials:
affiliation: Covance GFI Research, Evansville, IN 47714
name: Randall R Stoltz, MD
role: PRINCIPAL_INVESTIGATOR
References: