Diazepam nasal spray safe, convenient option for seizure control in kids

USA: Valtoco (NRL-1; Diazepam Nasal Spray) was safe, well-tolerated and had high bioavailability in patients with poor seizure control, according to a recent study presented at the American Epilepsy Society 2019 annual meeting. The pharmacokinetic profile of intranasal diazepam was generally comparable to rectal administration but with less interpatient variability.

Intranasal administration of Valtoco led to good diazepam exposure in patients on stable regimens of antiepileptic drugs who needed help in controlling bouts of increased seizure activity, the researchers reported at the meeting. Also, intranasal delivery is relatively easy, especially in an outpatient setting. Currently, diazepam is available as Diastat which is administered rectally and is not an ideal solution.

Despite the availability of chronic, daily oral medications to control epilepsy, it is estimated that 170,000 individuals in the United States are at risk for cluster or acute repetitive seizures. R. Edward Hogan, MD, of Washington University in St. Louis, and colleagues evaluated the relative comparability of pharmacokinetics and safety of NRL-1 (intranasal diazepam) in children with epilepsy during ictal/peri-ictal (seizure) and inter-ictal (non-seizure) periods.

The study enrolled 58 patients aged 6-59 years. The patients were diagnosed with partial or generalized epilepsy with motor seizures or seizures with clear alteration of awareness. Open-label intranasal NRL-1 was administered during two periods (ictal/peri-ictal, inter-ictal) ≥14 days apart. In both periods, one dose was administered (5, 10, 15, or 20 mg; based on weight), with a second dose permitted if seizures persisted.

Blood samples were taken at pre-specified timepoints after dosing, analyzed for diazepam, and pharmacokinetic measures were calculated. Safety was assessed.

Pharmacokinetic data were available from 10 children 6-11 years old (60% female, 80% white), and 4, 12-16 years old (75% female, 75% white).

Key findings of the study include:

• Pharmacokinetic values were similar under ictal/peri-ictal and inter-ictal conditions for both age groups.


• Among all 58 patients, 17 (29.3%) had ≥1 treatment-emergent adverse event (TEAE).


• Of these, 8 patients had treatment-related TEAEs with those reported in ≥2 patients being dysgeusia (n=3; 5.2%) and nasal discomfort (n=2; 3.4%); no local toxicity was observed.


• There were no serious TEAEs in children, and overall, only 1 patient had serious TEAEs (recurrent seizures, toxic encephalopathy), which were deemed unrelated to study treatment.


• No patient required a second dose for persistent seizures.

About VALTOCO

VALTOCO (diazepam nasal spray), is currently under review by the U.S. Food and Drug Administration as a treatment for intermittent use in adults and children 6 years and older with epilepsy, on stable regimens of antiepileptic drugs (AEDs), to control bouts of increased seizure activity, often referred to as cluster or acute repetitive seizures (ARS).

VALTOCO is a proprietary formulation of diazepam, incorporating the unique combination of a vitamin E–based solution and Intravail transmucosal absorption enhancement technology.

The study, "Pharmacokinetics and Safety of Valtoco (NRL-1; Diazepam Nasal Spray) in Children with Epilepsy During Seizure (Ictal/peri-ictal) and Non-seizure (Inter-ictal) Conditions: Results from a Phase 1, Open-Label Study," was presented at the American Epilepsy Society 2019 annual meeting.