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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.

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.

Condition or disease Intervention/treatment Phase
Thorough QT/QTc Study Drug: Inhaled loxapine Drug: Inhaled placebo Drug: Oral moxifloxacin Drug: Oral placebo Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double blind, double dummy
Primary Purpose: Treatment
Official Title: Thorough QT/QTc Study of Staccato® Loxapine for Inhalation in Healthy Volunteers
Study Start Date : April 2009
Actual Primary Completion Date : June 2009
Actual Study Completion Date : June 2009

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Treatment sequence ABC
Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
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

Treatment sequence ACB
Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
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

Treatment sequence BCA
Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
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

Treatment sequence BAC
Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
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

Treatment sequence CAB
Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
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

Treatment sequence CBA
Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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


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, 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



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:

  • 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.

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): NCT00874237


Locations
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United States, Indiana
Covance Clinical Research Unit Inc.
Evansville, Indiana, United States, 47710
Sponsors and Collaborators
Alexza Pharmaceuticals, Inc.
Investigators
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Principal Investigator: Randall R. Stoltz, MD Covance

Publications of Results:
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Responsible Party: Alexza Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00874237    
Other Study ID Numbers: AMDC-004-107
February 26, 2009
First Posted: April 2, 2009    Key Record Dates
Results First Posted: October 30, 2019
Last Update Posted: October 30, 2019
Last Verified: October 2019
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 ClinicalTrialsDoc@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.:
Staccato loxapine
QT/QTc
healthy volunteers
Thorough QT/QTc study
ADASUVE
inhaled loxapine
Additional relevant MeSH terms:
Layout table for MeSH terms
Moxifloxacin
Loxapine
Norgestimate, ethinyl estradiol drug combination
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents
Neurotransmitter Agents