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Staccato Prochlorperazine Thorough QT/QTc

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00543062
Recruitment Status : Completed
First Posted : October 12, 2007
Results First Posted : March 11, 2019
Last Update Posted : March 11, 2019
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Cardiotoxicity Drug: Inhaled placebo Drug: Oral placebo Drug: Inhaled prochlorperazine 5 mg Drug: Inhaled prochlorperazine 10 mg Drug: Oral moxifloxacin Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Female and male subjects in approximately equal numbers were randomly assigned (1:1:1:1) to receive the 4 treatment sequences
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: This was a double-blind, double dummy, placebo controlled, randomized 4-period crossover study to assess the effects of single doses of 5 and 10 mg of Staccato Prochlorperazine on QT intervals.
Primary Purpose: Treatment
Official Title: Thorough QT/QTc Study of Staccato® Prochlorperazine for Inhalation in Healthy Volunteers
Study Start Date : October 2007
Actual Primary Completion Date : December 2007
Actual Study Completion Date : December 2007

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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
Drug: Inhaled placebo
Inhaled Staccato placebo (0 mg)

Drug: Oral placebo
Oral placebo (identical to 400 mg moxifloxacin)

Drug: Inhaled prochlorperazine 5 mg
Staccato prochlorperazine 5 mg, single dose
Other Name: ADASUVE

Drug: Inhaled prochlorperazine 10 mg
Inhaled prochlorperazine 10 mg, single dose
Other Name: ADASUVE

Drug: Oral moxifloxacin
Oral moxifloxacin 400 mg, si/ngle dose

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
Drug: Inhaled placebo
Inhaled Staccato placebo (0 mg)

Drug: Oral placebo
Oral placebo (identical to 400 mg moxifloxacin)

Drug: Inhaled prochlorperazine 5 mg
Staccato prochlorperazine 5 mg, single dose
Other Name: ADASUVE

Drug: Inhaled prochlorperazine 10 mg
Inhaled prochlorperazine 10 mg, single dose
Other Name: ADASUVE

Drug: Oral moxifloxacin
Oral moxifloxacin 400 mg, si/ngle dose

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
Drug: Inhaled placebo
Inhaled Staccato placebo (0 mg)

Drug: Oral placebo
Oral placebo (identical to 400 mg moxifloxacin)

Drug: Inhaled prochlorperazine 5 mg
Staccato prochlorperazine 5 mg, single dose
Other Name: ADASUVE

Drug: Inhaled prochlorperazine 10 mg
Inhaled prochlorperazine 10 mg, single dose
Other Name: ADASUVE

Drug: Oral moxifloxacin
Oral moxifloxacin 400 mg, si/ngle dose

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
Drug: Inhaled placebo
Inhaled Staccato placebo (0 mg)

Drug: Oral placebo
Oral placebo (identical to 400 mg moxifloxacin)

Drug: Inhaled prochlorperazine 5 mg
Staccato prochlorperazine 5 mg, single dose
Other Name: ADASUVE

Drug: Inhaled prochlorperazine 10 mg
Inhaled prochlorperazine 10 mg, single dose
Other Name: ADASUVE

Drug: Oral moxifloxacin
Oral moxifloxacin 400 mg, si/ngle dose




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. Numbers and % of Subjects With QTcI > 450 ms [ Time Frame: 24 hours ]
    Numbers and Percents of Subjects with QTcI exceeding 450 ms

  3. 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

  4. 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

  5. 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


Other Outcome Measures:
  1. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00543062


Locations
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United States, Indiana
Covance Clinical Research Unit Inc.
Evansville, Indiana, United States, 47714
Sponsors and Collaborators
Alexza Pharmaceuticals, Inc.
Investigators
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Principal Investigator: Randall R Stoltz, MD Covance GFI Research, Evansville, IN 47714
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Responsible Party: Alexza Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00543062    
Other Study ID Numbers: AMDC-001-102
20 July 2007
First Posted: October 12, 2007    Key Record Dates
Results First Posted: March 11, 2019
Last Update Posted: March 11, 2019
Last Verified: November 2008
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD submitted to regulatory authorities. Others may contact Alexza Pharmaceuticals, Inc. Please send your request to ClinicalTrialsInfo@alexza.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Alexza Pharmaceuticals, Inc.:
Inhaled prochlorperazine, Thorough Qt/QTc,
Additional relevant MeSH terms:
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Cardiotoxicity
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Drug-Related Side Effects and Adverse Reactions
Chemically-Induced Disorders
Radiation Injuries
Wounds and Injuries
Moxifloxacin
Prochlorperazine
Loxapine
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents
Neurotransmitter Agents