ADASUVE-Lorazepam Drug-Drug Interaction

Condition(s) targeted: Healthy Volunteers

Intervention: ADASUVE 10 mg (Drug); Lorazepam 2 mg IM (Drug); Staccato Placebo (Drug); Placebo IM (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: Alexza Pharmaceuticals, Inc.

Official(s) and/or principal investigator(s):
Randall R Stoltz, MD, Principal Investigator, Affiliation: Medical Director, Covance-Evansville, Evansville, IN 47710

This study will compare the safety and effects over time for giving both ADASUVE and lorazepam (intramuscular) compared to that of each agent given alone.

Official title: ADASUVE®-Lorazepam Drug-Drug Interaction Study

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

Primary outcome: Pharmacodynamic effects on respiration

Secondary outcome:

Pharmacodynamic effects on vital signs

Pharmacodynamic effects on sedation

Pharmacodynamic effects on psychomotor measures

Detailed description: The objective of this study is to compare the safety and pharmacodynamic profiles of concomitant administration of a single dose of ADASUVE and lorazepam (IM) compared to that of each agent administered alone. Respiratory pharmacodynamics will be monitored through recordings of respirations/minute and pulse oximetry. Other pharmacodynamic safety measures will include effects on blood pressure, heart rate, sedation and psychomotor measures of attention, information processing speed, reaction time, and coordination. Initially, 4 subjects will receive lorazepam 1 mg IM + ADASUVE 10 mg open label to validate the dose regimen. After the safety data are reviewed and the dose regimen confirmed, 18 non-obese, healthy male or female volunteers between the ages of 18 and 50 will be enrolled in this double-blinded, double-dummy, randomized, 3-period cross-over drug interaction study.

Minimum age: 18 Years. Maximum age: 50 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Male and female subjects between the ages of 18 to 50 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 9 days.

- Subjects who speak, read, and understand English and are willing and able to provide

written informed consent on an IRB approved form prior to the initiation of any study procedures.

- Subjects who are in good general health prior to study participation as determined by

a detailed medical history, physical examination, 12-lead ECG, blood chemistry profile, hematology, urinalysis, and in the opinion of the Principal Investigator.

- Female participants (if of child-bearing potential and sexually active) who agree to

use a medically acceptable and effective birth control method throughout the study and for 30 days following the end of the study

- Male participants (if sexually active with a partner of child-bearing potential) who

agree to use a medically acceptable and effective birth control method from the first dose and for 90 days following last dose of study drug. Male participants must refrain from donating sperm for the same period. Exclusion Criteria:

- Subject history, which includes: any cardiovascular disease or disorder; asthma,

chronic obstructive lung disease, or any use of an inhaler prescribed for wheezing or bronchospasm must be excluded; sleep apnea; acute narrow-angle glaucoma; any neurological, gastrointestinal, hepatic, renal, hematologic, endocrine and/or metabolic disease or disorder; psychiatric illness or mental disorder except for short term situational anxiety or depression of < 2 years duration; any substance abuse or addiction within the last 2 years; pregnancy within the past 6 months.

- Subjects who have taken prescription or nonprescription medication within 7 days of

Visit 2.

- Subjects who have had an acute illness within the last 7 days of Visit 2.

- Subjects who have a history of HIV positivity.

- 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.

- Subjects who have a history of allergy or intolerance to lorazepam or any other

benzodiazepine.

- Subjects who have a history of allergy or intolerance to polyethylene glycol,

propylene glycol, or benzyl alcohol

- Female subjects who have a positive pregnancy test at screening or at admission to

Visit 2, or are breastfeeding.

- Subjects who have received an investigational drug within 30 days prior to the

Screening Visit.

- Subjects who have any other disease(s), by history, physical examination, or

laboratory abnormalities that, in the investigator's opinion, presents undue risk to the subject or may confound the interpretation of study results.

- Subjects who are considered by the investigator, for any reason, to be an unsuitable

candidate for receiving lorazepam or ADASUVE.

Covance-Evansville, Evansville, Indiana 47710, United States

Starting date: June 2013
Last updated: July 30, 2013