ADASUVE 2-dose Thorough QT/QTc Study

Alexza Pharmaceuticals, Inc.60 enrolled

Overview

Assess the potential effects on the QT interval of 2 consecutive doses of ADASUVE administered 2 hours apart, in relation to placebo and an active control in healthy volunteers.

It has been shown in a pre-marketing clinical study that clinically relevant QT prolongation does not appear to be associated with a single dose of ADASUVE. The potential risk of QTc prolongation following repeat dosing is unknown. Therefore the current study will assess the potential effects on the QT interval of 2 consecutive doses of ADASUVE administered 2 hours apart, in relation to placebo and an active control in healthy volunteers. The study hypothesis H0: Placebo-subtracted max mean dQTc \> 10 msec

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

QUADRUPLE

Enrollment

Conditions

Healthy Volunteers

Interventions

ADASUVE 10 mg 2 doses 2 hours apartDRUG

Inhaled loxapine 10 mg 2 doses 2 hours apart

Inhaled PlaceboDRUG

Staccato placebo via inhalation x 2 at 2 hours apart

Oral moxifloxacin 400 mgDRUG

Oral moxifloxacin 400 mg single dose

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Male and female subjects between the ages of 18 to 65 years, inclusive. * Body mass index (BMI) ≥18 and ≤32. * Subjects who are willing and able to comply with the study schedule and requirements, and stay at the CRU for a 4-day period and 2 consecutive 3-day periods. * Subjects who speak, read, and understand English and/or Dutch and are willing and able to provide written informed consent on an IEC approved form prior to the initiation of any study procedures. * Subjects who are in good general health prior to study participation * Female or male participants who agree to use a medically acceptable and effective birth control method Exclusion Criteria: * Subjects who regularly consume large amounts of xanthine-containing substances (≥ 5 cups of coffee/day). * Subjects who have taken prescription or nonprescription medication within 5 days of Visit 2. * Subjects who have had an acute illness within the last 5 days of Visit 2. * Subjects who have smoked tobacco within the last 30 days or who have a positive cotinine test. * Subjects who have a history of HIV, anti-HCV or HbsAg positivity. * Subjects who have a history within the past 2 years of drug or alcohol dependence or abuse as defined by DSM-IV. * Subjects who test positive for alcohol or have a positive urine drug screen. * Subjects who have a history of allergy or intolerance to loxapine or amoxapine or history of bronchospasm following inhaled loxapine treatment. * Subjects who have an ECG abnormality. * Subjects who have hypotension, or hypertension. * Subjects who have a history of unstable angina, syncope, coronary artery disease, myocardial infarction, congestive heart failure, transient ischemic attack, history of convulsions or other neurological disorder. * Subjects who have a current history of asthma, chronic obstructive lung disease, or any other lung disease associated with bronchospasm. * Subjects who use medications to treat airways disease, such as asthma or COPD. * Subjects who have any acute respiratory signs/symptoms (e.g., wheezing). * Female subjects who have a positive pregnancy test at screening or at admission to any of the treatment visits, or are breastfeeding. * Subjects who have received an investigational drug within 60 days prior to the Screening Visit.

Locations (1)

PRA International

Zuidlaren, Netherlands

Outcomes

Primary Outcomes

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

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 post-inhalation times.