Abstract Details

Title Safety and Pharmacodynamics of USL261, a Novel Formulation of Midazolam Optimized for Intranasal Administration

Topic Epilepsy

Presentation(s) P02 - (-)

Poster/Presentation
Number 211

Objective

Background BACKGROUND: Use of midazolam (MZ) carries a risk for excess sedation and/or decreased respiratory rate. USL261, a novel formulation of MZ optimized for easy and rapid administration intranasally (IN), is in development for outpatient rescue treatment of seizures.

Design/Methods DESIGN/METHODS: Healthy adult subjects (N=25) were randomly assigned to 1 of 5 MZ treatment sequences of a 5-way crossover study in which each subject received 2.5, 5.0, and 7.5 mg USL261 delivered by a unit-dose nasal spray device; 2.5 mg MZ for injection (MZ-inj; 5 mg/mL) administered via 15-min intravenous (IV) infusion; and 5.0 mg MZ-inj administered IN. Treatments were separated by ?3 days. Using validated instruments, assessments of sedation and psychomotor performance were conducted before and at predetermined times after study drug administration. Respiratory safety was assessed by monitoring vital signs and pulse oximetry. Tolerability was evaluated by reporting of treatment-emergent adverse events (TEAEs).

Results RESULTS: Sedation and psychomotor impairment increased with increasing doses of USL261. Mean peak changes from baseline occurred 30-75 min (sedation) and 10-20 min (psychomotor performance) after dosing. MZ-inj (5 mg) dosed IN resulted in similar results to USL261 5 mg. For all treatment groups, scores for each assessment returned to near baseline values by 4 hr. All subjects reported ?1 TEAE. All were mild in severity and occurred with similar frequency among the IN dosing groups; no TEAEs were reported in the IV group. The most commonly reported (by >20% of subjects) TEAEs were dysgeusia, increased lacrimation, nasal discomfort, and throat irritation. No subjects were observed to have a respiratory rate <8 breaths/min or O2 saturation <90%.

Conclusions CONCLUSIONS: All doses of USL261 were well-tolerated and did not result in excessive or prolonged sedation or psychomotor impairment. These results support the further development of USL261.

Authors/Disclosures
Heather A. Dworak (Upsher-smith Laboratoriesclinical Development) PRESENTER	No disclosure on file
	No disclosure on file
Mark Halvorsen, PharmD (Upsher-Smith Laboratories, LLC)	Dr. Halvorsen has received personal compensation for serving as an employee of Upsher-Smith Laboratories, LLC. Dr. Halvorsen has stock in Pfizer. Dr. Halvorsen has stock in Amgen. Dr. Halvorsen has stock in Stryker.
	No disclosure on file

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