Staccato Prochlorperazine Thorough QT/QTc

Cardiotoxicity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00543062
• Other study ID #: AMDC-001-102
• Secondary ID: 20 July 2007
• Status: Completed
• Phase: Phase 1
• Start date: October 2007
• Est. completion date: December 2007

Study information

• Verified date: November 2008
• Source: Alexza Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: December 2007
• Est. primary completion date: December 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cardiotoxicity

Intervention

Drug:
• Inhaled placebo
Inhaled Staccato placebo (0 mg)
• Oral placebo
Oral placebo (identical to 400 mg moxifloxacin)
• Inhaled prochlorperazine 5 mg
Staccato prochlorperazine 5 mg, single dose
• Inhaled prochlorperazine 10 mg
Inhaled prochlorperazine 10 mg, single dose
• Oral moxifloxacin
Oral moxifloxacin 400 mg, si/ngle dose

Locations

Country	Name	City	State
United States	Covance Clinical Research Unit Inc.	Evansville	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
Alexza Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Maximum Effect of Moxifloxacin on Cardiac Repolarization (QTc Interval Duration) Compared to Placebo (Study Assay Sensitivity)	A thorough QT/QTc study may be considered to have demonstrated assay sensitivity if 1 or more of the lower 95% CI values exceeds 5 msec	1, 1.5, 2, 2.5, 3, 5 hours
Primary	Maximum Effect of Inhaled Prochlorperazine on Cardiac Repolarization (QTc Interval Duration) at the Maximum Clinical Dose Compared to Placebo	Time-matched differences in QTcI values between the maximum of the mean difference from baseline of the QTcI interval after time-matched placebo subtraction for treatment at 11 post-inhalation times.	1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hr
Secondary	QTcI Versus Prochlorperazine Concentration	QTcI @ median prochlorperazine concentration (3.75 mcg/mL) based on linear and nonlinear regression of QTcI versus time matched serum prochlorperazine concentrations	1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hr
Secondary	Numbers and % of Subjects With QTcI > 450 ms	Numbers and Percents of Subjects with QTcI exceeding 450 ms	24 hours
Secondary	Numbers and % of Subjects With QTcI > 480 ms	Numbers and Percents of Subjects with QTcI exceeding 480 ms at any of the outcome measure time points	1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hr
Secondary	Numbers and % of Subjects With QTcI Change > 30 ms	Numbers and Percents of Subjects with QTcI increase from baseline exceeding 30 ms at any of the outcome measure time points	1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hr
Secondary	Numbers and % of Subjects With QTcI Change > 60 ms	Numbers and Percents of Subjects with QTcI increase from baseline exceeding 60 ms at any of the outcome measure time points	1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hr