Bioavailability, Safety and Tolerability of Diazepam Nasal Spray Versus Diazepam Rectal Gel (Diastat®)

Refractory Epilepsy Clinical Trial

Official title:

An Open-Label, Randomized, Crossover Pharmacokinetic Study to Determine the Bioavailability, Safety and Tolerability of Single Doses of Diazepam Nasal Spray Versus Diazepam Rectal Gel (Diastat®) in Patients With Refractory Epilepsy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02474407
• Other study ID #: DZNS-EP-1019
• Status: Terminated
• Phase: Phase 2
• Start date: June 2015
• Est. completion date: July 2016

Study information

• Verified date: September 2018
• Source: Acorda Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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)

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 78
• Est. completion date: July 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 65 Years

Eligibility

Inclusion Criteria:

• Diagnosis of refractory epilepsy

• Body weight 26 to 111 kilogram (kg) inclusive

• Other inclusion criteria apply

Exclusion Criteria:

• Male or female subject who is not surgically sterile or female subject who is less than 2 years postmenopausal, and does not agree to use a highly effective birth control method during the study and up to 3 months after the last dose of investigational product

• Female subject who is pregnant, breastfeeding, or planning to become pregnant

• Presence or history of any abnormality or illness that may affect the absorption, distribution, metabolism or elimination of diazepam

• Other exclusion criteria apply

Related Conditions & MeSH terms

• Drug Resistant Epilepsy
• Epilepsy
• Refractory Epilepsy

Intervention

Drug:
• diazepam nasal spray

• diazepam rectal gel

Locations

Country	Name	City	State
United States	Acorda Site #123	Amherst	New York
United States	Acorda Site #110	Ann Arbor	Michigan
United States	Acorda Site #111	Baltimore	Maryland
United States	Acorda Site #103	Bellaire	Texas
United States	Acorda Site #102	Bethesda	Maryland
United States	Acorda Site #132	Chapel Hill	North Carolina
United States	Acorda Site #122	Dallas	Texas
United States	Acorda Site #128	Edison	New Jersey
United States	Acorda Site #121	Hackensack	New Jersey
United States	Acorda Site #125	Honolulu	Hawaii
United States	Acorda Site #108	Houston	Texas
United States	Acorda Site #117	Jackson	Mississippi
United States	Acorda Site #104	Lexington	Kentucky
United States	Acorda Site #115	Little Rock	Arkansas
United States	Acorda Site #130	Memphis	Tennessee
United States	Acorda Site #105	Philadelphia	Pennsylvania
United States	Acorda Site #116	Philadelphia	Pennsylvania
United States	Acorda Site #114	Portland	Oregon
United States	Acorda Site #119	Rochester	New York
United States	Acorda Site #112	Saint Louis	Missouri
United States	Acorda Site #101	Tampa	Florida
United States	Acorda Site #127	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Acorda Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUC 0-24h	Relative bioavailability based on area under time plasma concentration curve.	24 hours
Primary	Cmax	Relative bioavailability based on maximum observed plasma concentration.	24 hours
Secondary	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)	pre-dose (day 1) up to 24 hours post-dose
Secondary	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)	pre-dose (day 1) up to 24 hours post-dose
Secondary	Smell Identification Test (SIT)	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.	day 1 up to day 31
Secondary	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.	Up to 24 hours

External Links

•   Click here for potential enrollment or for more information about this study: DZNS-EP-1019