ADASUVE-Lorazepam Drug-Drug Interaction (204-402)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Alexza Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01877642
First received: June 12, 2013
Last updated: July 30, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Healthy Volunteers
Drug: ADASUVE 10 mg
Drug: Lorazepam 2 mg IM
Drug: Staccato Placebo
Drug: Placebo IM
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Official Title: ADASUVE®-Lorazepam Drug-Drug Interaction Study

Resource links provided by NLM:


Further study details as provided by Alexza Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Pharmacodynamic effects on respiration [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
    The primary outcome measure will be change over time with a focus on the interval from baseline to 2 hours post treatment in respirations/minute and pulse oximetry between treatment groups (LS mean ratios and 90% CI for ADASUVE + lorazepam compared to ADASUVE and compared to lorazepam)


Secondary Outcome Measures:
  • Pharmacodynamic effects on vital signs [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
    Change over time in sitting systolic and diastolic blood pressure and heart rate between treatment groups (LS mean ratios and 90% CI for ADASUVE + lorazepam compared to ADASUVE and compared to lorazepam)

  • Pharmacodynamic effects on sedation [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
    Change over time in sedation via visual analog scale (VAS) between treatment groups (LS mean ratios and 90% CI for ADASUVE + lorazepam compared to ADASUVE and compared to lorazepam)

  • Pharmacodynamic effects on psychomotor measures [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
    Change over time in attention, information processing speed, reaction time, and coordination between treatment groups (LS mean ratios and 90% CI for ADASUVE + lorazepam compared to ADASUVE and compared to lorazepam)


Enrollment: 22
Study Start Date: June 2013
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Lorazepam IM
Lorazepam 2 mg IM + Staccato placebo
Drug: Lorazepam 2 mg IM
Other Name: Ativan 2 mg IM
Drug: Staccato Placebo
Inhaler with no drug in it to mimic the ADASUVE inhaler
Experimental: ADASUVE + Lorazepam
Lorazepam 2 mg IM + ADASUVE 10 mg
Drug: ADASUVE 10 mg
Other Name: Staccato Loxapine for Inhalation, 10 mg
Drug: Lorazepam 2 mg IM
Other Name: Ativan 2 mg IM
Active Comparator: ADASUVE
Placebo IM + ADASUVE 10 mg
Drug: ADASUVE 10 mg
Other Name: Staccato Loxapine for Inhalation, 10 mg
Drug: Placebo IM
placebo IM solution to mimic lorazepam 2 mg IM
Other Name: Saline

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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01877642

Locations
United States, Indiana
Covance-Evansville
Evansville, Indiana, United States, 47710
Sponsors and Collaborators
Alexza Pharmaceuticals, Inc.
Investigators
Principal Investigator: Randall R Stoltz, MD Medical Director, Covance-Evansville, Evansville, IN 47710
  More Information

No publications provided

Responsible Party: Alexza Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01877642     History of Changes
Other Study ID Numbers: AMDC-204-402
Study First Received: June 12, 2013
Last Updated: July 30, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Alexza Pharmaceuticals, Inc.:
ADASUVE
inhaled loxapine
drug drug interaction
lorazepam
acute treatment of agitation

Additional relevant MeSH terms:
Lorazepam
Loxapine
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hypnotics and Sedatives
Central Nervous System Depressants
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antipsychotic Agents
Dopamine Antagonists
Dopamine Agents

ClinicalTrials.gov processed this record on September 18, 2014