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

September 20, 2018 updated by: Acorda Therapeutics

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

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)

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

78

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Acorda Site #115
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Acorda Site #127
    • Florida
      • Tampa, Florida, United States, 33606
        • Acorda Site #101
    • Hawaii
      • Honolulu, Hawaii, United States, 96817
        • Acorda Site #125
    • Kentucky
      • Lexington, Kentucky, United States, 40513
        • Acorda Site #104
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Acorda Site #111
      • Bethesda, Maryland, United States, 20817
        • Acorda Site #102
    • Michigan
      • Ann Arbor, Michigan, United States, 48105
        • Acorda Site #110
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • Acorda Site #117
    • Missouri
      • Saint Louis, Missouri, United States, 63131
        • Acorda Site #112
    • New Jersey
      • Edison, New Jersey, United States, 08818
        • Acorda Site #128
      • Hackensack, New Jersey, United States, 07601
        • Acorda Site #121
    • New York
      • Amherst, New York, United States, 14226
        • Acorda Site #123
      • Rochester, New York, United States, 14642
        • Acorda Site #119
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Acorda Site #132
    • Oregon
      • Portland, Oregon, United States, 97239
        • Acorda Site #114
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Acorda Site #116
      • Philadelphia, Pennsylvania, United States, 19107
        • Acorda Site #105
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • Acorda Site #130
    • Texas
      • Bellaire, Texas, United States, 77401
        • Acorda Site #103
      • Dallas, Texas, United States, 75251
        • Acorda Site #122
      • Houston, Texas, United States, 77004
        • Acorda Site #108

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years to 65 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: diazepam nasal spray (DZNS)
One dose of diazepam nasal spray is administered as two intranasal sprays; one in each nostril using a nasal spray device.
Drug: diazepam nasal spray
Other Names:
  • Diazepam
Active Comparator: diazepam rectal gel (DRG)
A single rectal dose of diazepam will be administered to subjects according to the Diastat prescribing information.
Drug: diazepam rectal gel
Other Names:
  • Diastat®
  • AcuDial™

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
AUC 0-24h
Time Frame: 24 hours
Relative bioavailability based on area under time plasma concentration curve.
24 hours
Cmax
Time Frame: 24 hours
Relative bioavailability based on maximum observed plasma concentration.
24 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Focused Nasal Exam (Part A)
Time Frame: pre-dose (day 1) up to 24 hours post-dose

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
Focused Nasal Exam (Part B)
Time Frame: pre-dose (day 1) up to 24 hours post-dose

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
Smell Identification Test (SIT)
Time Frame: day 1 up to day 31
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
Taste Change Questionnaire
Time Frame: Up to 24 hours
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Acorda Therapeutics

Investigators

  • Study Director: Lee Min Jae, SK Biopharmaceuticals Co, Ltd

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2015

Primary Completion (Actual)

May 1, 2016

Study Completion (Actual)

July 1, 2016

Study Registration Dates

First Submitted

June 15, 2015

First Submitted That Met QC Criteria

June 15, 2015

First Posted (Estimate)

June 17, 2015

Study Record Updates

Last Update Posted (Actual)

October 16, 2018

Last Update Submitted That Met QC Criteria

September 20, 2018

Last Verified

September 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DZNS-EP-1019

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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