A Pharmacokinetic Study of a Single-Dose of Diazepam Nasal Spray in Adult Epileptic Patients Experiencing a Seizure Episode

Study Overview
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Brief Summary
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The purpose of this study is to determine the pharmacokinetics of Diazepam Nasal Spray following a single dose in epileptic patients experiencing a seizure episode.

Official Title
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An Open-Label Study to Determine the Pharmacokinetics of a Single Dose of Diazepam Nasal Spray in Adult Epileptic Patients Experiencing a Seizure Episode for Which Acute Treatment With a Benzodiazepine is Clinically Indicated

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: Diazepam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide signed informed consent for study participation. General good health with no clinically significant unstable abnormalities. Diagnosis of epilepsy. Exclusion Criteria: Individuals receiving warfarin (Coumadin®) or dabigatran (Pradaxa®). Use of any investigational drug within 30 days. Blood or plasma donation within 30 days. Not willing or unable to tolerate blood draws.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diazepam Nasal Spray<br> | Drug: Diazepam<br>* single-dose; dosage in mg, based on patient body weight<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) Parameter: Maximum Measure Plasma Concentration (Cmax), | Summary of Dose-Adjusted Diazepam and Nordiazepam PK parameter Cmax. The mean Cmax value was adjusted to a 20 mg dose. | Pre-dose, 10, 15, 30, and 45 mins, and 1, 1.5, 2, 4, 6, 9,and 12 hours | 
| Pharmacokinetic (PK) Parameter: Time to Maximum Plasma Concentration (Tmax) | Summary of Dose-Adjusted Diazepam and Nordiazepam PK parameter Tmax. The mean Tmax value was adjusted to a 20 mg dose. | Pre-dose, 10, 15, 30, and 45 mins, and 1, 1.5, 2, 4, 6, 9,and 12 hours | 
| Pharmacokinetic (PK) Parameter: Area Under The Concentration Curve From Time 0 to 12 Hours (AUC(0-12)) and AUC Time to Last Measurable Plasma Concentration | Summary of Dose-Adjusted Diazepam and Nordiazepam PK parameter AUC(0-12) and AUC(last). The mean estimate of AUC(0-12) was adjusted to a 20 mg dose. AUC(last) was used for the calculation of AUC for nordiazepam. AUC(0-12) values could not be estimated for nordiazepam given that nordiazepam concentrations were rising between 6 and 12 hours. | Pre-dose, 10, 15, 30, and 45 mins, and 1, 1.5, 2, 4, 6, 9,and 12 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Treatment Emergent Adverse Events (TEAEs) | TEAEs refer to adverse events with start dates occurring after dosing. Treatment-Related TEAEs refer to those 'possibly' or 'probably' related to study drug. Intensity definitions: Mild: Usually transient, required no special treatment, and did not interfere with the patient's daily activities. Moderate: Usually caused a low degree of inconvenience or concern to the patient, and may have interfered with daily activities, but was usually ameliorated by simple therapeutic measures. Severe: Interrupted a patient's usual daily activities, and generally required systemic drug therapy or other treatment. | Pre-dose to 48 hours post-dose |