ArticleEpilepsia2020
Pharmacokinetics and safety of VALTOCO (NRL-1; diazepam nasal spray) in patients with epilepsy during seizure (ictal/peri-ictal) and nonseizure (interictal) conditions: A phase 1, open-label study.
Article in Epilepsia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT02724423 (An Open-Label, Repeat-Dose Pharmacokinetics Study of NRL-1 in Epilepsy Subjects Under Seizure and Normal Conditions), which is not on this map. Cited by 39 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
An Open-Label, Repeat-Dose Pharmacokinetics Study of NRL-1 in Epilepsy Subjects Under Seizure and Normal Conditions
Who cites it
39 citing papers in PubMed, 50 citations in OpenAlex.
- Trial
- Pharmacokinetics and 180-day safety of diazepam nasal spray in pediatric patients with epilepsy aged 2-5 years.Epilepsia · 2025Trial
- Safety of Diazepam Nasal Spray in Pediatric Patients With Developmental Epileptic Encephalopathies: Results From a Long-term Phase 3 Safety Study.Journal of child neurology · 2023Trial
- Trial
- Trial
- Consistent safety and tolerability of ValtocoEpilepsia open · 2021Trial
- Trial
- Epilepsy: Molecular Pathogenesis and Emerging Therapies.MedComm · 2026Review
- Intranasal delivery route for neurodegenerative diseases: recent insights and future directions.Drug delivery and translational research · 2026Review
- Experimental study of the effects of diazepam on vasospasm in a subarachnoid rat model through pathological and biochemical analysis.Scientific reports · 2025Article
- Exploring proposed recommendations for immediate-use seizure medication: Treating both cluster and prolonged seizures with diazepam nasal spray.Epilepsia open · 2025Review
- Development of a novel dosing paradigm to model diazepam rescue therapy in preclinical seizure and epilepsy models.Epilepsia open · 2024Article
- Opportunities for Community Pharmacists to Counsel Patients With Epilepsy and Seizure Clusters to Overcome Barriers and Foster Appropriate Treatment.Journal of pharmacy practice · 2024Review
- Benzodiazepines for the Treatment of Seizure Clusters.CNS drugs · 2024Review
- Treatment of Seizure Clusters in Epilepsy: A Narrative Review on Rescue Therapies.Neurology and therapy · 2023Review
- Brain-Derived Neurotrophic Factor Dysregulation as an Essential Pathological Feature in Huntington's Disease: Mechanisms and Potential Therapeutics.Biomedicines · 2023Review
- Optimizing Absorption for Intranasal Delivery of Drugs Targeting the Central Nervous System Using Alkylsaccharide Permeation Enhancers.Pharmaceutics · 2023Review
- SipNose-topiramate: a potential novel approach to binge eating management.Journal of eating disorders · 2023Article
- Seizure Rescue Therapies: Comparing Approved and Commonly Used Benzodiazepine Formulations.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
- Translational Considerations in the Development of Intranasal Treatments for Epilepsy.Pharmaceutics · 2023Review
Corrections and comments
- Erratum issuedCorrigendum.2021
Authors and funding
8 authors at 6 institutions in 1 country.
Funding
Abstract
objectiveTo assess pharmacokinetics and safety of diazepam nasal spray (NRL-1; VALTOCO®) in pediatric and adult patients with epilepsy in seizure and nonseizure states.
methodsA single dose of diazepam nasal spray (5, 10, 15, or 20 mg based on weight) was administered during each of two conditions (ictal/peri-ictal and interictal condition) to patients 6-65 years old with partial or generalized epilepsy with motor seizures or seizures with clear alteration of awareness; a second dose was permitted if needed for persistent seizures. Dosing could be interictal or ictal/peri-ictal first, with a washout of ≥14 days. Blood samples for pharmacokinetic analysis were taken at prespecified time points. Treatment-emergent adverse events (TEAEs), sedation, nasal irritation, nasal mucosal pain, and olfactory changes were assessed.
resultsOf 57 patients in the study (mean age = 28.1 years [range = 6-59], 54.4% female, 80.7% white), 49 were included in the primary pharmacokinetic analyses. Diazepam pharmacokinetic profiles were similar under both conditions, with approximately 2-hour median time to mean (SD) maximum plasma concentrations of 164 (88) and 189 (110) ng/mL for ictal/peri-ictal and interictal conditions, respectively; drug exposure during the first 6 hours postdosing was 532 (313) and 615 (368) h•ng/mL, respectively. Seventeen patients (29.8%) reported TEAEs, of whom eight (14%) had treatment-related TEAEs, with those reported in ≥2 patients being dysgeusia (n = 3, 5.3%) and nasal discomfort (n = 2, 3.5%). One patient had serious TEAEs (recurrent seizures, metabolic encephalopathy), which were deemed unrelated to study treatment. No changes in respiratory rate were observed, nor were there clinically relevant changes in sedation, olfaction, nasal irritation, or acute nasal mucosal pain. SIGNIFICANCE: The epileptic conditions (ictal/peri-ictal, interictal) had minimal impact on diazepam nasal spray pharmacokinetics in patients with epilepsy. Therefore, diazepam nasal spray can be administered ictally and interictally. Diazepam nasal spray safety was consistent with the profile of diazepam.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.