QT/QTc Study of 2 Doses of ADASUVE�

Condition(s) targeted: Healthy Volunteers

Intervention: ADASUVE 10 mg 2 doses 2 hours apart (Drug); Oral moxifloxacin 400 mg (Drug); Staccato Placebo 2 doses 2 hours apart (Drug); Placebo (for moxifloxacin) (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: Alexza Pharmaceuticals, Inc.

Official(s) and/or principal investigator(s):
Teresa Nunes, MD, Principal Investigator, Affiliation: PRA Health Sciences

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

Official title: Thorough QT/QTc Study of 2 Doses of ADASUVE® in Healthy Volunteers

Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)

Primary outcome: Maximum effect of ADASUVE on cardiac repolarization (QTc interval duration) at the maximum clinical dose compared to placebo

Secondary outcome:

QTc versus loxapine concentration

Categorical analyses of QTcI outliers

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

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.

PRA International, Zuidlaren, Netherlands

Starting date: May 2013
Last updated: July 11, 2013