Staccato Prochlorperazine Thorough QT/QTc

Phase 1

Completed

• Conditions: Cardiotoxicity
• Interventions: Drug: Inhaled placebo; Drug: Oral placebo; Drug: Inhaled prochlorperazine 5 mg; Drug: Inhaled prochlorperazine 10 mg; Drug: Oral moxifloxacin

• Registration Number: NCT00543062
• Lead Sponsor: Alexza Pharmaceuticals, Inc.

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.

Study Timeline

• Study Start: 2007-10
• Study First Submitted: 2007-10-10
• Study First Submitted QC: 2007-10-10
• Study First Posted: 2007-10-12
• Primary Completion: 2007-12
• Study Completion: 2007-12
• Status Verified: 2008-11
• Results First Submitted: 2017-03-10
• Results First Submitted QC: 2018-11-19
• Last Update Submitted: 2018-11-19
• Results First Posted: 2019-03-11
• Last Update Posted: 2019-03-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 48

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Treatment Sequence DCBA	Inhaled prochlorperazine 5 mg	Treatment Sequence DCBA where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
Treatment Sequence DCBA	Inhaled prochlorperazine 10 mg	Treatment Sequence DCBA where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
Treatment Sequence BDAC	Inhaled prochlorperazine 5 mg	Treatment Sequence BDAC where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
Treatment Sequence ABCD	Oral moxifloxacin	Treatment Sequence ABCD where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
Treatment Sequence CABD	Oral moxifloxacin	Treatment Sequence CABD where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
Treatment Sequence ABCD	Inhaled placebo	Treatment Sequence ABCD where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
Treatment Sequence ABCD	Oral placebo	Treatment Sequence ABCD where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
Treatment Sequence BDAC	Oral moxifloxacin	Treatment Sequence BDAC where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
Treatment Sequence ABCD	Inhaled prochlorperazine 10 mg	Treatment Sequence ABCD where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
Treatment Sequence BDAC	Inhaled placebo	Treatment Sequence BDAC where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
Treatment Sequence BDAC	Oral placebo	Treatment Sequence BDAC where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
Treatment Sequence BDAC	Inhaled prochlorperazine 10 mg	Treatment Sequence BDAC where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
Treatment Sequence CABD	Inhaled placebo	Treatment Sequence CABD where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
Treatment Sequence DCBA	Oral placebo	Treatment Sequence DCBA where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
Treatment Sequence DCBA	Oral moxifloxacin	Treatment Sequence DCBA where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
Treatment Sequence ABCD	Inhaled prochlorperazine 5 mg	Treatment Sequence ABCD where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
Treatment Sequence CABD	Inhaled prochlorperazine 10 mg	Treatment Sequence CABD where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
Treatment Sequence DCBA	Inhaled placebo	Treatment Sequence DCBA where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
Treatment Sequence CABD	Oral placebo	Treatment Sequence CABD where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
Treatment Sequence CABD	Inhaled prochlorperazine 5 mg	Treatment Sequence CABD where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg

Primary Outcome Measures

Name	Time	Method
Maximum Effect of Inhaled Prochlorperazine on Cardiac Repolarization (QTc Interval Duration) at the Maximum Clinical Dose Compared to Placebo	1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hr	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.

Secondary Outcome Measures

Name	Time	Method
Numbers and % of Subjects With QTcI Change > 30 ms	1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hr	Numbers and Percents of Subjects with QTcI increase from baseline exceeding 30 ms at any of the outcome measure time points
Numbers and % of Subjects With QTcI > 450 ms	24 hours	Numbers and Percents of Subjects with QTcI exceeding 450 ms
Numbers and % of Subjects With QTcI > 480 ms	1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hr	Numbers and Percents of Subjects with QTcI exceeding 480 ms at any of the outcome measure time points
Numbers and % of Subjects With QTcI Change > 60 ms	1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hr	Numbers and Percents of Subjects with QTcI increase from baseline exceeding 60 ms at any of the outcome measure time points
QTcI Versus Prochlorperazine Concentration	1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hr	QTcI @ median prochlorperazine concentration (3.75 mcg/mL) based on linear and nonlinear regression of QTcI versus time matched serum prochlorperazine concentrations

Trial Locations

Locations (1)

Covance Clinical Research Unit Inc.; 🇺🇸 Evansville, Indiana, United States