Staccato Prochlorperazine Thorough QT/QTc

• 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: Alexza Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Alexza Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: October 10, 2007
• First Posted Date: October 12, 2007
• Results First Submitted Date: March 10, 2017
• Results First Posted Date: March 11, 2019
• Last Update Posted Date: March 11, 2019
• Study Start Date: October 2007
• Actual Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 19, 2018)

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.

• Original Primary Outcome Measures (submitted: October 10, 2007): Time-matched differences in changes from baseline for each treatment vs. placebo QTc [ Time Frame: At each post-treatment time point ]

Current Secondary Outcome Measures (submitted: November 19, 2018)

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

• Original Secondary Outcome Measures (submitted: October 10, 2007): Categorical analysis of incidence of numbers and percents of subjects with absolute values and changes from baseline [ Time Frame: At each post-treatment time point ]

Current Other Pre-specified Outcome Measures (submitted: November 19, 2018)

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

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Staccato Prochlorperazine Thorough QT/QTc
• Official Title: Thorough QT/QTc Study of Staccato® Prochlorperazine for Inhalation in Healthy Volunteers
• 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 Type: Interventional
• Study Phase: Phase 1

Study Design

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

• Condition: Cardiotoxicity

Intervention

• 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

Study Arms

• 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
  Interventions:

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

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

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

  • Drug: Inhaled placebo
  • Drug: Oral placebo
  • Drug: Inhaled prochlorperazine 5 mg
  • Drug: Inhaled prochlorperazine 10 mg
  • Drug: Oral moxifloxacin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 10, 2007): 48
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: December 2007
• Actual Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00543062
• Other Study ID Numbers: AMDC-001-102; 20 July 2007
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

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

• Current Responsible Party: Alexza Pharmaceuticals, Inc.
• Original Responsible Party: Not Provided
• Current Study Sponsor: Alexza Pharmaceuticals, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Randall R Stoltz, MD; Covance GFI Research, Evansville, IN 47714

• PRS Account: Alexza Pharmaceuticals, Inc.
• Verification Date: November 2008