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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
QUADRUPLE
Enrollment
22
Lorazepam 1 mg intramuscular
Inhaled Staccato loxapine 10 mg
Inhaler with no drug in it to mimic the ADASUVE inhaler
Covance-Evansville
Evansville, Indiana, United States
Maximum Level of Sedation for Lorazepam 1 mg IM + ADASUVE 10 mg
Determine the maximum level of sedation for Lorazepam 1 mg IM + ADASUVE 10 mg based on the 100 mm Visual Analog Scale (VAS) ranging from (0=sleepy to 100=wide awake)
Time frame: 24 hours
Relative Pharmacodynamic Effect on Respiration Rate for Combined vs Individual (Lorazepam, Loxapine)
LS Mean ratio (90% CI) of the area under the curve for 0 to 24 hours (AUC 0-24) for respiration rate following administration of Lorazepam+Loxapine compared to the same measure following each control drug given alone (Lorazepam, Loxapine)
Time frame: 24 hours
Relative Pharmacodynamic Effect on Systolic Blood Pressure for Combined vs Individual (Lorazepam, Loxapine)
LS Means ratio (90% CI) of the area under the curve for 0 to 24 hours (AUC 0-24) for systolic blood pressure following administration of Lorazepam+Loxapine compared to the same measure following each control drug (Lorazepam, Loxapine) given alone
Time frame: 24 hours
Relative Pharmacodynamic Effect on Sedation for Combined vs Individual (Lorazepam, Loxapine)
LS Means ratio (90% CI) of the area under the curve for 0 to 24 hours (AUC 0-24) for sedation based on a 100 mm Visual Analog Scale (VAS) ranging from (0=sleepy to 100=wide awake) following administration of Lorazepam+Loxapine compared to the same measure following each control drug given alone (Lorazepam, Loxapine)
Time frame: 24 hours
Relative Pharmacodynamic Effect on Pulse Oximetry for Combined vs Individual (Lorazepam, Loxapine)
LS Means ratio (90% CI) of the area under the curve for 0 to 24 hours (AUC 0-24) for pulse oximetry following administration of Lorazepam+Loxapine compared to the same measure following each control drug (Lorazepam, Loxapine) given alone
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intramuscular placebo to mimic lorazepam 1 mg IM
Time frame: 24 hours
Relative Pharmacodynamic Effect on Heart Rate for Combined vs Individual (Lorazepam, Loxapine)
LS Means ratio (90% CI) of the area under the curve for 0 to 24 hours (AUC 0-24) for heart rate following administration of Lorazepam+Loxapine compared to the same measure following each control drug (Lorazepam, Loxapine) given alone
Time frame: 24 hours
Relative Pharmacodynamic Effect on Diastolic Blood Pressure for Combined vs Individual (Lorazepam, Loxapine)
LS Means ratio (90% CI) of the area under the curve for 0 to 24 hours (AUC 0-24) for diastolic blood pressure following administration of Lorazepam+Loxapine compared to the same measure following each control drug (Lorazepam, Loxapine) given alone
Time frame: 24 hours
Relative Pharmacodynamic Effect on Cogscreen Pathfinder Response for Combined vs Individual (Lorazepam, Loxapine)
LS Means ratio (90% CI) of the area under the curve for 0 to 24 hours (AUC 0-24) for Cogscreen Pathfinder Response following administration of Lorazepam+Loxapine compared to the same measure following each control drug (Lorazepam, Loxapine) given alone
Time frame: 24 hours