Analysis of long-term safety of intranasal diazepam shows favorable results in children and adolescents with cluster or acute, repetitive seizures.
Eric Segal, MD
Data from an interim analysis of a phase 3 trial of intranasal diazepam (Valtoco; Neurelis) show a favorable safety and tolerability profile in children and adolescents with epilepsy. The results were presented at the 2019 Child Neurology Society Annual Meeting, October 23-26, 2019, in Charlotte, North Carolina.
The open-label, 12-month repeat dose study included 28 children age 6 to 11, and 21 adolescents age 12 to 17 treated for cluster or acute, repetitive seizures. The study evaluated long-term safety and tolerability of intranasal diazepam at doses of 5, 10, 15, or 20 mg, with a second dose, if necessary, administered 4 to 12 hours later. Within the group examined, 19 (38.8%) patients had exposure to intranasal diazepam for at least 6 months, while 16 (32.7%) had exposure for at least 12 months. Overall, 29 patients (59.2%) averaged 2 or more doses per month.
Study outcomes included treatment-emergent adverse events (TEAES), as well as physical/ neurological examinations, vital signs, laboratory tests, nasal irritation, and smell tests.
Ultimately, results of the study showed that 22 children (78.6%) and 12 adolescents (57.1%) had at least 1 TEAE. Notably, while 11 (39.3%) children and 6 adolescents (28.6%) reported serious TEAEs, none were associated with the study drug.
Of the 2 groups examined, 2 children and 5 adolescents reported a treatment-related TEAE, including irritation, epistaxis, sedation, somnolence, nasal mucosal disorder, rash, and sleep disorder. Notably, few patients experienced nasal irritation, and no clinically relevant changes in sense of smell were reported. There were no trends observed in the incidence of the most frequent TEAEs, as well as no trends in effects on hematology and chemistry/urinalysis values. No electrocardiographic abnormalities were observed, as well.
“Intranasal medications used during the preictal state pose several advantages over rectal diazepam (which until recently was the only FDA-approved emergency therapy available). It is likely that medication would be administered faster, especially for patients who have adult weight and habitus,” Eric Segal, MD, co-director of Epileptology, Hackensack Meridian Health, told NeurologyLive. “Additionally, many adult patients only used oral benzodiazepines instead of the approved rectal. With less stigma associated with a nasal formulation, it is likely that more patients will have emergency medications readily available. Faster access and availability will hopefully prevent the potential sequel associated with seizures.”
Segal, who is also director of pediatric epilepsy at Northeast Regional Epilepsy Group, believes that if approved, intranasal diazepam would give patients more treatment choices and help prevent injury and hospitalization. Valtoco is currently still under review with the FDA, but Neurelis anticipates a hearing with the agency by the end of the year.
Segal E, Tarquinio D, Miller I, Dlugos D, Wheless J, Carrazana E, for the DIAZ 001.04 Study Group. Safety of Valtoco™ (NRL-1; diazepam nasal spray) in children and adolescents with epilepsy: interim subgroup results from a phase 3, open-label, 12-month repeat dose study. Presented at: 2019 Child Neurology Society Annual Meeting. October 23-26, 2019; Charlotte, NC. Abstract 60.