Low Rate of Medication Errors Supports the Ability of Patients and Caregivers to Administer NRL-1, an Intranasal Formulation of Diazepam: Interim Results from a Phase 3, Open-Label, Repeat Dose Study

Objective: To determine extent and type of dosing errors as proxy for the ability of patients/caregivers to properly administer NRL-1. Background: NRL-1 (Valtoco®), a diazepam nasal spray formulated with Intravail A3, provides a rapid, non-invasive route of administration as rescue treatment in patients with epilepsy who experience seizures despite stable antiepileptic drug regimens. Design/Methods: Pediatric and adult patients with epilepsy having seizures despite a stable antiepileptic regimen were administered NRL-1 (5, 10, 15, or 20 mg based on weight), with a second dose administered as needed 4–12 hours later; investigators could adjust doses for efficacy/safety. The 5 and 10 mg doses required single spray into one nostril; the 15 and 20 mg doses required a spray into each nostril. Patients/Caregivers recorded dosing times, outcomes, and dosing errors in a diary that was used to evaluate their ability to administer NRL-1. Safety was evaluated. Results: Among 132 patients (mean±SD age: 25.7±15.1 years; 53.8% female; 82.6% white), 2486 doses of NRL-1 were administered; 191 (8.4%) of 2274 seizures treated required a second dose. Patients/Caregivers reported 31 dosing errors (23 patients), accounting for 1.2% of administered doses. Of these errors, 80.6% were associated with doses requiring spray into both nostrils, and 4 patients had multiple errors. Partial dosing accounted for 48.4% of errors, 12.9% were improper dosing time, 9.7% were mechanical errors, and 29.0% were other/unknown. Overall in this study, 91 patients (68.9%) had a treatment-emergent adverse event (TEAE). No adverse events have been reported related to dosing errors. Conclusions: These results suggest the ability of patients/caregivers to readily administer NRL-1 during seizure clusters, although dosing errors from either over- or under-dosing occurred in a small percentage of patients. Most errors occurred during doses that required administration into both nostrils. The safety profile was consistent with other studies.