This is a multi-center, open-label, crossover, pharmacokinetic, bio-availability study involving adolescents and adults with refractory (drug-resistant) epilepsy. Cohort 1 comprises the subjects used to determine the relative bioavailability of DZNS versus DRG (Diastat)
To determine the bioavailability of diazepam nasal spray versus diazepam rectal gel (Diastat®) under conditions of use in adolescent and adult persons with epilepsy (PWE) meeting the definition of refractory epilepsy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
78
Acorda Site #115
Little Rock, Arkansas, United States
Acorda Site #127
AUC 0-24h
Relative bioavailability based on area under time plasma concentration curve.
Time frame: 24 hours
Cmax
Relative bioavailability based on maximum observed plasma concentration.
Time frame: 24 hours
Focused Nasal Exam (Part A)
A focused nasal exam was completed by the Investigator in the treatment period(s) when diazepam nasal spray was administered, based on a visual inspection of the nasal mucosa. Nasal irritation will be graded "none" to Grade 4 "septal perforation." Grade 1a= focal irritation, Grade 1b= superficial mucosal erosion, Grade 2= moderate mucosal erosion, Grade 3= ulceration, Grade 4= septal perforation. This exam may be conducted within a 5 minute window after the specified time point. Between the 12 and 24 h time points, the exam should be repeated every 4 hours as needed to follow any residual symptoms to resolution and the time of resolution should be documented. (Categories with no data were omitted)
Time frame: pre-dose (day 1) up to 24 hours post-dose
Focused Nasal Exam (Part B)
A focused nasal exam was completed by the Investigator in the treatment period(s) when diazepam nasal spray was administered, based on a visual inspection of the nasal mucosa. Focused Nasal Examination Part B - will show nasal mucosal symptoms that will be rated for severity will include discharge, mucosal edema, crusting, erythema, and epistaxis. This exam may be conducted within a 5 minute window after the specified time point. Between the 12 and 24 h time points, the exam was should be repeated every 4 hours as needed to follow any residual symptoms to resolution and the time of resolution should be documented. (Categories with no data were omitted)
Time frame: pre-dose (day 1) up to 24 hours post-dose
Smell Identification Test (SIT)
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Washington D.C., District of Columbia, United States
Acorda Site #101
Tampa, Florida, United States
Acorda Site #125
Honolulu, Hawaii, United States
Acorda Site #104
Lexington, Kentucky, United States
Acorda Site #111
Baltimore, Maryland, United States
Acorda Site #102
Bethesda, Maryland, United States
Acorda Site #110
Ann Arbor, Michigan, United States
Acorda Site #117
Jackson, Mississippi, United States
Acorda Site #112
St Louis, Missouri, United States
...and 12 more locations
The SIT is a validated test of smell identification which scores patients into different levels of olfactory function normalized by age and gender, however it had not been validated for use in PWE. The Smell Identification Test (SIT) is a 40-item multiple-choice standardized test. The test can be self-administered and consists of four 10-page booklets with a different "scratch and sniff" strip on each page. A scratch with a pencil releases the scent from the strip, and the subject is then asked to match the scent to one of four choices on the page. An answer must be selected for each of the 40 items, even when the subject cannot detect a smell. The total score (i.e., number of correct answers, range: 0-40) can be compared against normative data collected from approximately 4000 normal individuals between ages 4 to 99 to determine the subject's percentile rank of olfactory dysfunction corrected for age and gender.
Time frame: day 1 up to day 31
Taste Change Questionnaire
Questionnaire given to safety population in Cohort 1 for reporting taste change during the study. If the subject spontaneously reports an experience of taste change associated with diazepam nasal spray dosing, it will be evaluated qualitatively by the research staff using a taste change questionnaire. The subject will be asked to describe the type, intensity, and duration of the change in taste at multiple scheduled time points after dosing. Between the 12 and 24 h time points, the questionnaire should be repeated every 4 hours as needed to follow any residual symptoms to resolution, and time of resolution should be documented.
Time frame: Up to 24 hours