Upsher-Smith Laboratories has announced positive phase I data for USL261 (investigational intranasal midazolam) in patients with epilepsy. Results demonstrated that USL261 at a single dose of up to 7.5mg was rapidly absorbed and exhibited a short half-life. Additionally, USL261 generally was well-tolerated in patients with epilepsy and demonstrated a rapid onset of pharmacodynamic effects with return to baseline function by four hours post dose.

USL261 is an investigational formulation of midazolam being developed for the intranasal rescue treatment of seizures in patients who require control of intermittent bouts of increased seizure activity, including seizure clusters or acute repetitive seizures.  It is intended to be delivered intranasally without active inhalation by the patient.

USL261 has been granted Orphan Drug Designation for this use by the FDA and currently is the subject of a global phase III clinical trial—ARTEMIS1—being conducted under a Special Protocol Assessment (SPA) agreement with the FDA. An open-label safety extension study to ARTEMIS1 also is underway. The multicenter study will evaluate the long-term safety and tolerability of USL261 in the treatment of seizure clusters.

“Patients and caregivers need alternatives, such as intranasal formulations, to rectal diazepam, the only approved out-of-hospital treatment for bouts of increased seizures. The results of a recently completed phase I study of USL261 in patients show that the investigational drug, given at clinically relevant doses, is rapidly absorbed with an onset of pharmacodynamic effects within 10 minutes following administration,” said James Cloyd, PharmD, professor and Lawrence C. Weaver Endowed Chair-Orphan Drug Development, department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota. Adverse effects appeared modest and were consistent with known benzodiazepine adverse effects. Findings presented at AAN support the continued development of USL261 for outpatient rescue treatment of seizures in patients who require control of intermittent bouts of increased seizure activity.”

The randomized, phase 1, open-label, inpatient study enrolled 90 patients with epilepsy between the ages of 12 and 65 years old on stable antiepileptic drug (AED) regimens. Patients were administered a single dose of 2.5mg, 5mg or 7.5mg USL261 by unit-dose nasal-spray.