[P3.277] Safety and Pharmacodynamics of USL261, a Novel Intranasal Formulation of Midazolam, in Subjects with Epilepsy
Robert Hayes,1Lindy Bancke,2Heather Dworak1
1Morristown, NJ, USA, 2Maple Grove, MN, USA
To assess the safety and degree/duration of sedation and psychomotor performance impairment following a single dose of USL261 in subjects with epilepsy on a stable antiepileptic drug regimen.
USL261 is an investigational formulation of midazolam optimized for intranasal delivery for outpatient treatment of patients requiring control of intermittent bouts of increased seizure activity (eg, seizure clusters, or acute repetitive seizures).
This randomized, phase 1, open-label, inpatient study enrolled 90 subjects (12-65 years old) administered a single dose of USL261 2.5, 5.0, or 7.5 mg by a unit-dose nasal-spray device. Sedation was assessed pre- and up to 12 hours post dose using the Stanford Sleepiness Scale (SSS) and Observer's Assessment of Alertness/Sedation Scale (OAA/S); psychomotor performance impairment was evaluated using the Digit Symbol Substitution Test (DSST). Safety, including respiratory rate and pulse oximetry, was monitored.
Signs of sedation were evident 10 min after dosing, with mean peak sedation scores occurring between 1 and 2 hr for SSS and in <1 hr for OAA/S. The peak effect on mean % correct DSST scores occurred approximately 30 min after dosing and increased with increasing dose. DSST scores returned to baseline by 3 hours after dosing, while SSS and OAA/S returned to near baseline levels by 4 hours post dose. Largely mild/moderate treatment-emergent adverse events were reported, with the most common (>10% of subjects) being dysgeusia, oropharyngeal pain, rhinalgia, and burning sensation.
USL261 at a single dose of up to 7.5 mg was well tolerated without prolonged/excessive sedation or psychomotor performance impairment effects in adult and adolescent subjects with epilepsy. Onset of pharmacodynamic effects was rapid (as early as 10 minutes post dose) with return to baseline function by 4 hours post dose, supporting further development for treatment of patients with intermittent bouts of increased seizure activity.
STUDY SUPPORTED BY: Upsher-Smith Laboratories, Inc.
Category - Epilepsy and Clinical Neurophysiology (EEG): Other
Tuesday, April 29, 2014 3:00 PM
P3: Poster Session III: Epilepsy and Clinical Neurophysiology: AED (3:00 PM-6:30 PM)