Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| diazepam rectal gel (DRG) | Active Comparator | A single rectal dose of diazepam will be administered to subjects according to the Diastat prescribing information. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| diazepam nasal spray | Drug |
|
| |
| diazepam rectal gel |
| Measure | Description | Time Frame |
|---|---|---|
| AUC 0-24h | Relative bioavailability based on area under time plasma concentration curve. | 24 hours |
| Cmax | Relative bioavailability based on maximum observed plasma concentration. | 24 hours |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Lee Min Jae | SK Biopharmaceuticals Co, Ltd | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Acorda Site #115 | Little Rock | Arkansas | 72205 | United States | ||
| Acorda Site #127 |
Not provided
This is a randomized crossover study with 78 subjects total.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Single Dose of Diazapam Nasal Spray (DZNS) | Subjects received a single dose diazepam nasal spray (DZNS) followed by a washout period of 14 days, after which a single dose of diazapam rectal gel (DRG) was administered. |
| FG001 | Single Dose of Diazapam Rectal Gel (DRG) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| First Intervention (14 Days) |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Drug |
|
|
| 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) | 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. | 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. | Up to 24 hours |
| Washington D.C. |
| District of Columbia |
| 20010 |
| United States |
| Acorda Site #101 | Tampa | Florida | 33606 | United States |
| Acorda Site #125 | Honolulu | Hawaii | 96817 | United States |
| Acorda Site #104 | Lexington | Kentucky | 40513 | United States |
| Acorda Site #111 | Baltimore | Maryland | 21201 | United States |
| Acorda Site #102 | Bethesda | Maryland | 20817 | United States |
| Acorda Site #110 | Ann Arbor | Michigan | 48105 | United States |
| Acorda Site #117 | Jackson | Mississippi | 39216 | United States |
| Acorda Site #112 | St Louis | Missouri | 63131 | United States |
| Acorda Site #128 | Edison | New Jersey | 08818 | United States |
| Acorda Site #121 | Hackensack | New Jersey | 07601 | United States |
| Acorda Site #123 | Amherst | New York | 14226 | United States |
| Acorda Site #119 | Rochester | New York | 14642 | United States |
| Acorda Site #132 | Chapel Hill | North Carolina | 27599 | United States |
| Acorda Site #114 | Portland | Oregon | 97239 | United States |
| Acorda Site #116 | Philadelphia | Pennsylvania | 19104 | United States |
| Acorda Site #105 | Philadelphia | Pennsylvania | 19107 | United States |
| Acorda Site #130 | Memphis | Tennessee | 38105 | United States |
| Acorda Site #103 | Bellaire | Texas | 77401 | United States |
| Acorda Site #122 | Dallas | Texas | 75251 | United States |
| Acorda Site #108 | Houston | Texas | 77004 | United States |
Subjects received a single dose of Diazepam Rectal Gel (DRG) followed by a washout period of 14 days, after which a single dose of diazapam nasal spray (DZNS) was administered. |
| COMPLETED |
|
| NOT COMPLETED |
|
| Washout (14 Days) |
|
| Second Intervention (14 Days) |
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | DZNS (Diazepam Nasal Spray) vs DRG (Diazepam rectal gel) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | AUC 0-24h | Relative bioavailability based on area under time plasma concentration curve. | Posted | Mean | Standard Deviation | ng*h/mL | 24 hours |
|
|
| |||||||||||||||||||||||||||||
| Primary | Cmax | Relative bioavailability based on maximum observed plasma concentration. | Posted | Mean | Standard Deviation | ng/mL | 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) | Safety population Cohort 1. (Accessed only for DZNS Arm) | Posted | Count of Participants | Participants | 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) | The Safety population / Cohort 1. (Accessed only for DZNS Arm) | Posted | Count of Participants | Participants | 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. | Safety Population / Cohort 1. (Accessed only for DZNS Arm) | Posted | Count of Participants | Participants | 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. | Safety Population / Cohort 1. (Accessed only for DZNS Arm) | Posted | Mean | Standard Deviation | units on a scale | Up to 24 hours |
|
|
31 Days
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Diazepam Nasal Spray | One dose of diazepam nasal spray is administered as two intranasal sprays; one in each nostril using a nasal spray device. Diazepam Nasal Spray | 0 | 78 | 0 | 78 | 60 | 78 |
| EG001 | Diazepam Rectal Gel | A single rectal dose of diazepam will be administered to subjects according to the Diastat prescribing information. Diazepam Rectal Gel | 0 | 78 | 0 | 78 | 20 | 78 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasal Discomfort | General disorders | Systematic Assessment |
| ||
| Dysgeusia | General disorders | Systematic Assessment |
| ||
| Lacrimation Increased | General disorders | Systematic Assessment |
| ||
| Nasal Mucosal Disorder | General disorders | Systematic Assessment |
| ||
| Rhinorrhea | General disorders | Systematic Assessment |
| ||
| Edema Mucosal | General disorders | Systematic Assessment |
| ||
| Throat irritation | General disorders | Systematic Assessment |
| ||
| Somnolence | Nervous system disorders | Systematic Assessment |
| ||
| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Rhinalgia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Headache | Nervous system disorders | Systematic Assessment |
| ||
| Abdominal Pain | Gastrointestinal disorders | Systematic Assessment |
| ||
| Anorectal discomfort | Gastrointestinal disorders | Systematic Assessment |
| ||
| Dysphagia | Gastrointestinal disorders | Systematic Assessment |
| ||
| Oral dysesthesia | Gastrointestinal disorders | Systematic Assessment |
| ||
| Feeling Hot | General disorders | Systematic Assessment |
| ||
| Mucosal erosion | General disorders | Systematic Assessment |
| ||
| Pyrexia | General disorders | Systematic Assessment |
| ||
| Secretion discharge | General disorders | Systematic Assessment |
| ||
| Gastroenteritis viral | Infections and infestations | Systematic Assessment |
| ||
| Tonsillitis | Infections and infestations | Systematic Assessment |
| ||
| White blood cell count | Investigations | Systematic Assessment |
| ||
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Aura | Nervous system disorders | Systematic Assessment |
| ||
| Burning sensation | Nervous system disorders | Systematic Assessment |
| ||
| Dizziness | Nervous system disorders | Systematic Assessment |
| ||
| Paresthesia | Nervous system disorders | Systematic Assessment |
| ||
| Parosmia | Nervous system disorders | Systematic Assessment |
| ||
| Sinus headache | Nervous system disorders | Systematic Assessment |
| ||
| Epistaxis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Sneezing | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Hiccups | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Acne | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Hyperhidrosis | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Skin irritation | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding the study results for a period up to 30 days from the date the communication is submitted to the sponsor. The sponsor shall have the right to defer proposed publication an additional 60 days from the end of the review period. The sponsor cannot require changes to the communication and cannot unilaterally extend the embargo.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Lee Min Jae, Associate Manager | SK Bio-pharmaceuticals Co, Ltd | minj.lee@sk.com |
| ID | Term |
|---|---|
| D000069279 | Drug Resistant Epilepsy |
| D012640 | Seizures |
| D004827 | Epilepsy |
| ID | Term |
|---|---|
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| D003975 | Diazepam |
| ID | Term |
|---|---|
| D001570 | Benzodiazepinones |
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
One dose of diazepam nasal spray is administered as two intranasal sprays; one in each nostril using a nasal spray device. diazepam nasal spray |
| OG003 | DZNS - At 24 Hours Post-Dose - Grade 2 | One dose of diazepam nasal spray is administered as two intranasal sprays; one in each nostril using a nasal spray device. diazepam nasal spray |
| OG004 | DZNS - At 24 Hours Post-Dose - Grade 3 | One dose of diazepam nasal spray is administered as two intranasal sprays; one in each nostril using a nasal spray device. diazepam nasal spray |
| OG005 | DZNS - At 24 Hours Post-Dose - Grade 4 | One dose of diazepam nasal spray is administered as two intranasal sprays; one in each nostril using a nasal spray device. diazepam nasal spray |
| OG006 | DZNS - At 24 Hours Post-Dose - Missing | One dose of diazepam nasal spray is administered as two intranasal sprays; one in each nostril using a nasal spray device. diazepam nasal spray |
|
|
One dose of diazepam nasal spray is administered as two intranasal sprays; one in each nostril using a nasal spray device. diazepam nasal spray |
| OG003 | DZNS - At 24 Hours Post-Dose Severe | One dose of diazepam nasal spray is administered as two intranasal sprays; one in each nostril using a nasal spray device. diazepam nasal spray |
| OG004 | DZNS - At 24 Hours Post-Dose Missing | One dose of diazepam nasal spray is administered as two intranasal sprays; one in each nostril using a nasal spray device. diazepam nasal spray |
|
|
| OG002 |
| At Follow-Up Visit - Moderate Microsmia |
Shift in SIT Scores in Cohort 1 from Treatment Period 1 (Prior to Dosing) to Follow-up Visit |
| OG003 | At Follow-Up Visit - Severe Microsmia | Shift in SIT Scores in Cohort 1 from Treatment Period 1 (Prior to Dosing) to Follow-up Visit |
| OG004 | At Follow-Up Visit - Anosmia | Shift in SIT Scores in Cohort 1 from Treatment Period 1 (Prior to Dosing) to Follow-up Visit |
| OG005 | At Follow-Up Visit - Probable Malingering | Shift in SIT Scores in Cohort 1 from Treatment Period 1 (Prior to Dosing) to Follow-up Visit |
| OG006 | At Follow-Up Visit - Missing | Shift in SIT Scores in Cohort 1 from Treatment Period 1 (Prior to Dosing) to Follow-up Visit |
|
|
|