Refractory EpilepsyPhase 2NCT02474407
Bioavailability, Safety and Tolerability of Diazepam Nasal Spray Versus Diazepam Rectal Gel (Diastat®)
A Phase 2 study testing diazepam nasal spray and diazepam rectal gel in people with Refractory Epilepsy, run by Acorda Therapeutics at 22 sites in United States.
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) Read more about this study
- Who is it for?
- Ages 12 to 65 years
- Conditions the study is for
- Refractory Epilepsy
- What is being tested?
- diazepam nasal spray and diazepam rectal gel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 22 sitesUnited States
- Study dates
- Jun 2015to Jul 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Diagnosis of refractory epilepsy
- Body weight 26 to 111 kilogram (kg) inclusive
- Other inclusion criteria apply
Who cannot join
- 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
Trial locations and contacts
22 sites in 1 country.
22 sites in 1 country
United States22 sites
Acorda Site #123
Amherst, New York, 14226
Acorda Site #110
Ann Arbor, Michigan, 48105
Acorda Site #111
Baltimore, Maryland, 21201
Acorda Site #103
Bellaire, Texas, 77401
Acorda Site #102
Bethesda, Maryland, 20817
Acorda Site #132
Chapel Hill, North Carolina, 27599
Acorda Site #122
Dallas, Texas, 75251
Acorda Site #128
Edison, New Jersey, 08818
Acorda Site #121
Hackensack, New Jersey, 07601
Acorda Site #125
Honolulu, Hawaii, 96817
Acorda Site #108
Houston, Texas, 77004
Acorda Site #117
Jackson, Mississippi, 39216
Acorda Site #104
Lexington, Kentucky, 40513
Acorda Site #115
Little Rock, Arkansas, 72205
Acorda Site #130
Memphis, Tennessee, 38105
Acorda Site #116
Philadelphia, Pennsylvania, 19104
Acorda Site #105
Philadelphia, Pennsylvania, 19107
Acorda Site #114
Portland, Oregon, 97239
Acorda Site #119
Rochester, New York, 14642
Acorda Site #112
St Louis, Missouri, 63131
Acorda Site #101
Tampa, Florida, 33606
Acorda Site #127
Washington D.C., District of Columbia, 20010
About this study
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
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)
Read the 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.
- Conditions
- Refractory Epilepsy
- Being tested
- diazepam nasal spray, diazepam rectal gel
- Keywords
- Seizures, Epilepsy
- Medical subject headings
- Drug Resistant Epilepsy, Seizures, Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
diazepam nasal sprayDrug
Also called Diazepam
diazepam rectal gelDrug
Also called Diastat®, AcuDial™
| Study group | Role | What they receive |
|---|---|---|
| diazepam nasal spray (DZNS) | Experimental | One dose of diazepam nasal spray is administered as two intranasal sprays; one in each nostril using a nasal spray device. Receives: Drug: diazepam nasal spray |
| diazepam rectal gel (DRG) | Active comparator | A single rectal dose of diazepam will be administered to subjects according to the Diastat prescribing information. Receives: Drug: diazepam rectal gel |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC 0-24h
Relative bioavailability based on area under time plasma concentration curve.
Measured: 24 hours
Cmax
Relative bioavailability based on maximum observed plasma concentration.
Measured: 24 hours
Secondary outcomes (4)
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)
Measured: 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)
Measured: pre-dose (day 1) up to 24 hours post-dose
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.
Measured: 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.
Measured: Up to 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2015 (estimated)
- Study startJun 2015
- Primary completionMay 2016
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Refractory EpilepsyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- Acorda Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Lee Min Jae, Study director, SK Biopharmaceuticals Co, Ltd
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02474407
- Sponsor's protocol ID
- DZNS-EP-1019
- Status last verified
- Sep 2018
- First submitted
- 15 Jun 2015
- Last updated
- 16 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02474407
- Acronym / sponsor ID
- DZNS-EP-1019
- Conditions
- Refractory Epilepsy
- Keywords
- Seizures, Epilepsy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 78 participants (actual)
- Lead sponsor
- Acorda TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Jun 2015
- Primary completion
- May 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 17 Jun 2015 (estimated)
- Results
- Posted 16 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| diazepam nasal spray (DZNS) | Experimental | Drug: diazepam nasal sprayOne dose of diazepam nasal spray is administered as two intranasal sprays; one in each nostril using a nasal spray device. |
| diazepam rectal gel (DRG) | Active comparator | Drug: diazepam rectal gelA single rectal dose of diazepam will be administered to subjects according to the Diastat prescribing information. |
Who may qualify
- Ages
- 12 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Diagnosis of refractory epilepsy
- Body weight 26 to 111 kilogram (kg) inclusive
- Other inclusion criteria apply
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| diazepam nasal sprayAlso: Diazepam | Drug | diazepam nasal spray (DZNS) |
| diazepam rectal gelAlso: Diastat®, AcuDial™ | Drug | diazepam rectal gel (DRG) |
Primary outcome
AUC 0-24h
Time frame: 24 hours
Relative bioavailability based on area under time plasma concentration curve.
Cmax
Time frame: 24 hours
Relative bioavailability based on maximum observed plasma concentration.
4 secondary outcomes
Focused Nasal Exam (Part A)
Time frame: 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
Smell Identification Test (SIT)
Time frame: day 1 up to day 31
Taste Change Questionnaire
Time frame: Up to 24 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Refractory Epilepsy
Not yet recruiting
Clinical Trial of SEEG for Drug-resistant Epilepsy
Drug-Resistant Epilepsy
Recruiting
Identification of Biomarkers for Vagus Nerve Stimulation in Patients With Refractory Epilepsy
Refractory Epilepsy
Not yet recruiting
Electrophysiological Dose-Response to Anterior Thalamic Deep Brain Stimulation in Drug-Resistant Focal Epilepsy
Drug Resistant Epilepsy, Focal Epilepsy
Recruiting
Effect of Blue Light on Vagus Nerve Stimulation in Patients With Refractory Epilepsy
Refractory Epilepsy
RecruitingPhase 1
Investigation of Blood-Brain-Barrier Breakdown Using Manganese Magnetic Resonance Imaging in Drug-Resistant Epilepsy
Epilepsy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lee Min Jae study director
SK Biopharmaceuticals Co, Ltd
22 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing diazepam nasal spray and diazepam rectal gel in people with Refractory Epilepsy, run by Acorda Therapeutics at 22 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AUC 0-24h (time frame: 24 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2018.