Staccato Loxapine Thorough QT/QTc Study

Thorough QT/QTc Study of Staccato® Loxapine for Inhalation in Healthy Volunteers

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.

Study Overview

• Status: Completed
• Conditions: Thorough QT/QTc Study
• Intervention / Treatment: Drug: Inhaled loxapine; Drug: Inhaled placebo; Drug: Oral moxifloxacin; Drug: Oral placebo

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: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Evansville, Indiana, United States, 47710
      • Covance Clinical Research Unit Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 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 Names: 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
Other: 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 Names: 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
Other: 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 Names: 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
Other: 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 Names: 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
Other: 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 Names: 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
Other: 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 Names: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Effect of ADASUVE on Cardiac Repolarization (QTc Interval Duration) at the Maximum Clinical Dose Compared to Placebo	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	1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 23 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac Repolarization Change (QTcI) Versus Loxapine Concentration Relationship Following Treatment With Staccato Loxapine in Healthy Volunteers.	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.	24 hours
Numbers and % of Subjects With QTcI > 450 ms	Numbers and Percents of Subjects with QTcI exceeding 450 ms	1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 23 hours
Numbers and % of Subjects With QTcI > 480 ms	Numbers and Percents of Subjects with QTcI exceeding 480 ms	1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 23 hours
Numbers and % of Subjects With QTcI Change > 30 ms	Numbers and Percents of Subjects with QTcI increase from baseline exceeding 30 ms	1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 23 hours
Numbers and % of Subjects With QTcI Change > 60 ms	Numbers and Percents of Subjects with QTcI increase from baseline exceeding 60 ms	1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 23 hours

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)	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	1, 1.5, 2, 2.5, 3, 5, 8, 12, and 24 hr

Collaborators and Investigators

• Sponsor: Alexza Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Randall R. Stoltz, MD, Covance

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: April 1, 2009
• First Submitted That Met QC Criteria: April 1, 2009
• First Posted (Estimate): April 2, 2009

Study Record Updates

• Last Update Posted (Actual): October 30, 2019
• Last Update Submitted That Met QC Criteria: October 29, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: healthy volunteers; QT/QTc; inhaled loxapine; ADASUVE; Staccato loxapine; Thorough QT/QTc study
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Central Nervous System Depressants; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Dopamine Agents; Dopamine Antagonists; Moxifloxacin; Loxapine
• Other Study ID Numbers: AMDC-004-107; February 26, 2009

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 ClinicalTrialsDoc@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