Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Staccato Loxapine Thorough QT/QTc Study

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: NCT00874237
Recruitment Status : Completed
First Posted : April 2, 2009
Results First Posted : October 30, 2019
Last Update Posted : October 30, 2019
Sponsor:
Information provided by (Responsible Party):
Alexza Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE April 1, 2009
First Posted Date  ICMJE April 2, 2009
Results First Submitted Date  ICMJE March 13, 2017
Results First Posted Date  ICMJE October 30, 2019
Last Update Posted Date October 30, 2019
Study Start Date  ICMJE April 2009
Actual Primary Completion Date June 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 29, 2019)
Maximum Effect of ADASUVE 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 23 hours ]
Largest of the upper CIs of the 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 ADASUVE treatment at 12 prespecified post inhalation times
Original Primary Outcome Measures  ICMJE
 (submitted: April 1, 2009)
Time-matched average differences in QTc between active drug and placebo [ Time Frame: 24 hours ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 29, 2019)
  • Cardiac Repolarization Change (QTcI) Versus Loxapine Concentration Relationship Following Treatment With Staccato Loxapine in Healthy Volunteers. [ Time Frame: 24 hours ]
    QTcI change at the median loxapine concentration (32.2 mcg/mL) based on nonlinear regression of QTcI versus log of time matched serum loxapine concentrations. This analysis looks for repolarization versus concentration relationship in a positive or negative thorough QT/QTc study result.
  • Numbers and % of Subjects With QTcI > 450 ms [ Time Frame: 1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 23 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 23 hours ]
    Numbers and Percents of Subjects with QTcI exceeding 480 ms
  • Numbers and % of Subjects With QTcI Change > 30 ms [ Time Frame: 1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 23 hours ]
    Numbers and Percents of Subjects with QTcI increase from baseline exceeding 30 ms
  • Numbers and % of Subjects With QTcI Change > 60 ms [ Time Frame: 1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 23 hours ]
    Numbers and Percents of Subjects with QTcI increase from baseline exceeding 60 ms
Original Secondary Outcome Measures  ICMJE
 (submitted: April 1, 2009)
QTc versus loxapine concentration relationship following treatment with Staccato Loxapine in healthy volunteers. [ Time Frame: 24 hours ]
Current Other Pre-specified Outcome Measures
 (submitted: October 29, 2019)
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, 8, 12, and 24 hr ]
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 ant any of the 9 predetermined time points
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Staccato Loxapine Thorough QT/QTc Study
Official Title  ICMJE Thorough QT/QTc Study of Staccato® Loxapine for Inhalation in Healthy Volunteers
Brief Summary The purpose of the present Phase 1 study was to assess the cardiac safety of Staccato Loxapine administered to healthy volunteers in a 3 period crossover study.
Detailed Description

Primary Objective: To assess the maximum effect of Staccato Loxapine on cardiac repolarization (QTc interval duration) at the anticipated maximum clinical dose compared to placebo in healthy volunteers.

Secondary Objective: To assess the QTc versus loxapine concentration relationship following treatment with Staccato Loxapine in healthy volunteers.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Double blind, double dummy
Primary Purpose: Treatment
Condition  ICMJE Thorough QT/QTc Study
Intervention  ICMJE
  • Drug: Inhaled loxapine
    Inhaled Staccato Loxapine 10 mg single dose
    Other Name: ADASUVE
  • Drug: Inhaled placebo
    Inhaled Staccato placebo single dose
  • Drug: Oral moxifloxacin
    Oral moxifloxacin 400 mg
  • Drug: Oral placebo
    Oral placebo similar in appearance to moxifloxacin 400 mg
Study Arms  ICMJE
  • Treatment sequence ABC
    Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
    Interventions:
    • Drug: Inhaled loxapine
    • Drug: Inhaled placebo
    • Drug: Oral moxifloxacin
    • Drug: Oral placebo
  • Treatment sequence ACB
    Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
    Interventions:
    • Drug: Inhaled loxapine
    • Drug: Inhaled placebo
    • Drug: Oral moxifloxacin
    • Drug: Oral placebo
  • Treatment sequence BCA
    Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
    Interventions:
    • Drug: Inhaled loxapine
    • Drug: Inhaled placebo
    • Drug: Oral moxifloxacin
    • Drug: Oral placebo
  • Treatment sequence BAC
    Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
    Interventions:
    • Drug: Inhaled loxapine
    • Drug: Inhaled placebo
    • Drug: Oral moxifloxacin
    • Drug: Oral placebo
  • Treatment sequence CAB
    Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
    Interventions:
    • Drug: Inhaled loxapine
    • Drug: Inhaled placebo
    • Drug: Oral moxifloxacin
    • Drug: Oral placebo
  • Treatment sequence CBA
    Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
    Interventions:
    • Drug: Inhaled loxapine
    • Drug: Inhaled placebo
    • Drug: Oral moxifloxacin
    • Drug: Oral placebo
Publications * Spyker DA, Voloshko P, Heyman ER, Cassella JV. Loxapine delivered as a thermally generated aerosol does not prolong QTc in a thorough QT/QTc study in healthy subjects. J Clin Pharmacol. 2014 Jun;54(6):665-74. doi: 10.1002/jcph.257. Epub 2014 Jan 22.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 1, 2009)
48
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 2009
Actual Primary Completion Date June 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subjects who are in good general health and agree to use a medically acceptable and effective birth control method throughout the study.

Exclusion Criteria:

  • Subjects who have taken prescription or nonprescription medication within 5 days of treatment,
  • Subjects who have had an acute illness within the last 5 days of treatment,
  • Subjects who are smokers, OR
  • Subjects who have an ECG abnormality at baseline.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00874237
Other Study ID Numbers  ICMJE AMDC-004-107
February 26, 2009
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  ICMJE
Plan to Share IPD: Yes
Plan Description: IPD submitted to regulatory authorities. Others may contact Alexza Pharmaceuticals, Inc. Please send your request to ClinicalTrialsDoc@alexza.com
Responsible Party Alexza Pharmaceuticals, Inc.
Study Sponsor  ICMJE Alexza Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Randall R. Stoltz, MD Covance
PRS Account Alexza Pharmaceuticals, Inc.
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP