Study Design of an Open-Label Pharmacokinetic and Safety Trial of Diazepam Nasal Spray (Valtoco®) in Children 2–5 Years Old with Seizure Clusters
Abstract number :
1.287
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2021
Submission ID :
1825580
Source :
www.aesnet.org
Presentation date :
12/4/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:43 AM
Authors :
Miguel Lopez-Toledano, PhD - Neurelis, Inc.; Cynthia Guerra, MBA - Neurelis, Inc.; Sunita Misra, MD, PhD - Neurelis, Inc.; Enrique Carrazana, MD - Neurelis, Inc.; Adrian Rabinowicz, MD - Neurelis, Inc.
Rationale: Diazepam nasal spray (Valtoco®) is approved for acute treatment of seizure clusters in patients with epilepsy aged ≥6 years. A previous pharmacokinetic (PK) study showed diazepam nasal spray had similar bioavailability but less interpatient variability compared with diazepam rectal gel in healthy adult volunteers. In a study of patients aged 6–65 years with epilepsy, diazepam nasal spray showed similar PK profiles in interictal versus ictal/peri-ictal periods. In a long-term phase 3 safety study of patients aged 6–65 years, diazepam nasal spray had a safety profile consistent with that of rectal gel.
Younger children also may require out-of-hospital treatment for seizure clusters. There are limited data on the PK of diazepam in children, with no pediatric data available for rectal gel, which is approved for patients aged ≥2 years. Diazepam nasal spray represents another diazepam formulation that may be easier to use and could potentially provide more predictable blood levels than rectal gel in this population. A study was designed to elucidate the PK profile and repeated-dose safety of diazepam nasal spray in patients aged 2–5 years with seizure clusters.
Methods: This open-label safety study consists of a screening and baseline period, a single-dose period to evaluate PK, and a 180-day treatment period (Figure). A single dose will be administered during an interictal period to collect blood samples for PK analysis (predose to 6 hours postdose). Following the PK period, diazepam nasal spray will be administered for seizure clusters for 180 days, and an electronic diary will be used to record seizure occurrence, diazepam nasal spray use, and adverse events (AEs). Follow-up safety visits (including nasal irritation assessment) occur at Days 30, 90, and 180, with follow-up phone calls at Days 60, 120, 150, and 187 to collect AEs.
Children (2–5 years) with partial or generalized epilepsy with motor seizures or seizures with clear alteration of awareness who may need a benzodiazepine for seizure control and are frequent users of rescue medication are eligible. Patients with weight < 6 kg or >33 kg and any medical or psychiatric condition that would jeopardize safety are excluded. Dosing (5-, 10-, or 15-mg diazepam nasal spray) is based on body weight. Half of the cohort (aged 4–5 years) will be enrolled initially, followed by the rest of the cohort (aged 2–3 years).
Noncompartmental analysis will be used to calculate Cmax, tmax, and AUC(0‑6). PK modeling will be a component of this analysis. Safety data will be summarized.
Results: Currently, only 1 treatment is approved for children aged 2–5 years, and further treatment options are needed. This study will provide novel data on the PK and safety profile of diazepam nasal spray in this young population.
Conclusions: This study is important for evaluating the safety and PK profile of diazepam nasal spray in patients aged 2–5 years with seizure clusters and will clarify the potential value of diazepam nasal spray in this younger age group.
Funding: Please list any funding that was received in support of this abstract.: Neurelis, Inc.
Anti-seizure Medications