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

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.

IPD submitted to regulatory authorities. Others may contact Alexza Pharmaceuticals, Inc. Please send your request to ClinicalTrialsInfo@alexza.com

Safety Population (N=60)

From first exposure to study treatment to 30 days after last exposure to study treatment

Adverse events (AEs) were assessed pre-dose and at 12 prespecified time points

The use of healthy subjects, which precludes observation of drug-induced QTc prolongation in a population with additional factors predisposing to TdP. Subjects with respiratory disease were excluded.