Staccato Loxapine Thorough QT/QTc Study

Phase 1

Completed

Conditions: Thorough QT/QTc Study

Interventions: Drug: Inhaled loxapine
Drug: Inhaled placebo
Drug: Oral moxifloxacin
Drug: Oral placebo

Registration Number: NCT00874237

Lead Sponsor: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 48

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 & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Treatment sequence ABC	Inhaled loxapine	Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
Treatment sequence ABC	Inhaled placebo	Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
Treatment sequence BCA	Oral moxifloxacin	Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
Treatment sequence ABC	Oral placebo	Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
Treatment sequence ABC	Oral moxifloxacin	Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
Treatment sequence ACB	Oral moxifloxacin	Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
Treatment sequence ACB	Oral placebo	Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
Treatment sequence BCA	Inhaled loxapine	Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
Treatment sequence BCA	Inhaled placebo	Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
Treatment sequence ACB	Inhaled loxapine	Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
Treatment sequence ACB	Inhaled placebo	Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
Treatment sequence BCA	Oral placebo	Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
Treatment sequence BAC	Inhaled loxapine	Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
Treatment sequence BAC	Inhaled placebo	Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
Treatment sequence BAC	Oral moxifloxacin	Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
Treatment sequence BAC	Oral placebo	Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
Treatment sequence CAB	Inhaled loxapine	Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
Treatment sequence CAB	Inhaled placebo	Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
Treatment sequence CAB	Oral moxifloxacin	Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
Treatment sequence CAB	Oral placebo	Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
Treatment sequence CBA	Inhaled loxapine	Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
Treatment sequence CBA	Inhaled placebo	Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
Treatment sequence CBA	Oral moxifloxacin	Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg
Treatment sequence CBA	Oral placebo	Treatment: A = Inhaled loxapine 10 mg, B = Placebo, C = Oral moxifloxacin 400 mg

Primary Outcome Measures

Name	Time	Method
Maximum Effect of ADASUVE on Cardiac Repolarization (QTc Interval Duration) at the Maximum Clinical Dose Compared to Placebo	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

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