- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00543062
Staccato Prochlorperazine Thorough QT/QTc
November 19, 2018 updated by: Alexza Pharmaceuticals, Inc.
Thorough QT/QTc Study of Staccato® Prochlorperazine for Inhalation in Healthy Volunteers
To assess the safety of Staccato Prochlorperazine on cardiac repolarization (QTc interval duration) at 2 dose levels compared to placebo in healthy volunteers.
Study Overview
Status
Completed
Conditions
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 Type
Interventional
Enrollment (Actual)
48
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Indiana
-
Evansville, Indiana, United States, 47714
- Covance Clinical Research Unit Inc.
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Male and female subjects between the ages of 18 to 65 years, inclusive.
- Body mass index (BMI) ≥21 and ≤30.
- 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.
- 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.
- 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.
- 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:
- Subjects who regularly consume large amounts of xanthine-containing substances must be excluded.
- Subjects who have taken prescription or nonprescription medication within 5 days of Treatment Period 1 must be excluded.
- Subjects who have had an acute illness within the last 5 days of Treatment Period 1 must be excluded.
- Subjects who have smoked tobacco within the last year must be excluded.
- Subjects who have a history of HIV positivity must be excluded.
- Subjects who have a history of allergy or intolerance to prochlorperazine or phenothiazines must be excluded.
- Subjects who have a history of contraindication to anticholinergics must be excluded.
- Subjects who have a history of pheochromocytoma, seizure disorder, Parkinson's disease, or Restless Leg Syndrome must be excluded.
- Subjects who have an ECG abnormality must be excluded.
- 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.
- 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.
- Subjects who have a history of asthma or chronic obstructive lung disease must be excluded.
- Subjects who have hypotension (systolic ≤90 mmHg, diastolic ≤50 mmHg), or hypertension (systolic ≥140 mmHg, diastolic blood pressure ≥90 mmHg) must be excluded.
- Subjects who test positive for alcohol or have a positive urine drug screen must be excluded.
- Female subjects who have a positive pregnancy test at screening or during randomization visit, or are breastfeeding must be excluded.
- Subjects who have received an investigational drug within 30 days prior to the Screening Visit must be excluded.
- 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.
- 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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Treatment Sequence ABCD
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
|
Inhaled Staccato placebo (0 mg)
Oral placebo (identical to 400 mg moxifloxacin)
Staccato prochlorperazine 5 mg, single dose
Other Names:
Inhaled prochlorperazine 10 mg, single dose
Other Names:
Oral moxifloxacin 400 mg, si/ngle dose
|
Other: Treatment Sequence BDAC
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
|
Inhaled Staccato placebo (0 mg)
Oral placebo (identical to 400 mg moxifloxacin)
Staccato prochlorperazine 5 mg, single dose
Other Names:
Inhaled prochlorperazine 10 mg, single dose
Other Names:
Oral moxifloxacin 400 mg, si/ngle dose
|
Other: Treatment Sequence CABD
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
|
Inhaled Staccato placebo (0 mg)
Oral placebo (identical to 400 mg moxifloxacin)
Staccato prochlorperazine 5 mg, single dose
Other Names:
Inhaled prochlorperazine 10 mg, single dose
Other Names:
Oral moxifloxacin 400 mg, si/ngle dose
|
Other: Treatment Sequence DCBA
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
|
Inhaled Staccato placebo (0 mg)
Oral placebo (identical to 400 mg moxifloxacin)
Staccato prochlorperazine 5 mg, single dose
Other Names:
Inhaled prochlorperazine 10 mg, single dose
Other Names:
Oral moxifloxacin 400 mg, si/ngle dose
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Effect of Inhaled Prochlorperazine on Cardiac Repolarization (QTc Interval Duration) at the Maximum Clinical Dose Compared to Placebo
Time Frame: 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.
|
1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hr
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
QTcI Versus Prochlorperazine Concentration
Time Frame: 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
|
1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hr
|
Numbers and % of Subjects With QTcI > 450 ms
Time Frame: 24 hours
|
Numbers and Percents of Subjects with QTcI exceeding 450 ms
|
24 hours
|
Numbers and % of Subjects With QTcI > 480 ms
Time Frame: 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
|
1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hr
|
Numbers and % of Subjects With QTcI Change > 30 ms
Time Frame: 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
|
1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hr
|
Numbers and % of Subjects With QTcI Change > 60 ms
Time Frame: 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
|
1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hr
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Effect of Moxifloxacin on Cardiac Repolarization (QTc Interval Duration) Compared to Placebo (Study Assay Sensitivity)
Time Frame: 1, 1.5, 2, 2.5, 3, 5 hours
|
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
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Randall R Stoltz, MD, Covance GFI Research, Evansville, IN 47714
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
October 1, 2007
Primary Completion (Actual)
December 1, 2007
Study Completion (Actual)
December 1, 2007
Study Registration Dates
First Submitted
October 10, 2007
First Submitted That Met QC Criteria
October 10, 2007
First Posted (Estimate)
October 12, 2007
Study Record Updates
Last Update Posted (Actual)
March 11, 2019
Last Update Submitted That Met QC Criteria
November 19, 2018
Last Verified
November 1, 2008
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Chemically-Induced Disorders
- Pathologic Processes
- Heart Diseases
- Cardiovascular Diseases
- Wounds and Injuries
- Drug-Related Side Effects and Adverse Reactions
- Radiation Injuries
- Cardiotoxicity
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Central Nervous System Depressants
- Autonomic Agents
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Antineoplastic Agents
- Antiemetics
- Gastrointestinal Agents
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Anti-Bacterial Agents
- Antipsychotic Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Dopamine Agents
- Dopamine Antagonists
- Moxifloxacin
- Loxapine
- Prochlorperazine
Other Study ID Numbers
- AMDC-001-102
- 20 July 2007
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
IPD submitted to regulatory authorities.
Others may contact Alexza Pharmaceuticals, Inc. Please send your request to ClinicalTrialsInfo@alexza.com
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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