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Trial record 94 of 146 for:    epilepsy AND Bethesda

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02474407
Recruitment Status : Terminated
First Posted : June 17, 2015
Results First Posted : October 16, 2018
Last Update Posted : October 16, 2018
Sponsor:
Information provided by (Responsible Party):
Acorda Therapeutics

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Refractory Epilepsy
Interventions Drug: diazepam nasal spray
Drug: diazepam rectal gel
Enrollment 78
Recruitment Details This is a randomized crossover study with 78 subjects total.
Pre-assignment Details  
Arm/Group Title Single Dose of Diazapam Nasal Spray (DZNS) Single Dose of Diazapam Rectal Gel (DRG)
Hide Arm/Group Description 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. 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.
Period Title: First Intervention (14 Days)
Started 39 39
Completed 39 39
Not Completed 0 0
Period Title: Washout (14 Days)
Started 39 39
Completed 39 39
Not Completed 0 0
Period Title: Second Intervention (14 Days)
Started 39 39
Completed 39 39
Not Completed 0 0
Arm/Group Title All Participants
Hide Arm/Group Description DZNS (Diazepam Nasal Spray) vs DRG (Diazepam rectal gel)
Overall Number of Baseline Participants 78
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 78 participants
<=18 years
2
   2.6%
Between 18 and 65 years
75
  96.2%
>=65 years
1
   1.3%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 78 participants
41.4  (13.52)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 78 participants
Female
51
  65.4%
Male
27
  34.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 78 participants
Hispanic or Latino
5
   6.4%
Not Hispanic or Latino
73
  93.6%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 78 participants
American Indian or Alaska Native
1
   1.3%
Asian
1
   1.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
13
  16.7%
White
57
  73.1%
More than one race
0
   0.0%
Unknown or Not Reported
6
   7.7%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 78 participants
78
 100.0%
1.Primary Outcome
Title AUC 0-24h
Hide Description Relative bioavailability based on area under time plasma concentration curve.
Time Frame 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Single Dose of Diazapam Nasal Spray (DZNS) Single Dose of Diazapam Rectal Gel (DRG)
Hide Arm/Group Description:
Single, weight-based dose (0.2mg/kg) of DZNS and DRG administered in two randomly assigned treatment periods, separated by a minimum 14-day washout period per intervention.
Single, weight-based dose (0.2mg/kg) of DZNS and DRG administered in two randomly assigned treatment periods, separated by a minimum 14-day washout period per intervention.
Overall Number of Participants Analyzed 78 78
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
1357.7  (802.78) 2117.9  (996.27)
2.Primary Outcome
Title Cmax
Hide Description Relative bioavailability based on maximum observed plasma concentration.
Time Frame 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Single Dose of Diazapam Nasal Spray (DZNS) Single Dose of Diazapam Rectal Gel (DRG)
Hide Arm/Group Description:
Single, weight-based dose (0.2mg/kg) of DZNS and DRG administered in two randomly assigned treatment periods, separated by a minimum 14-day washout period per intervention.
Single, weight-based dose (0.2mg/kg) of DZNS and DRG administered in two randomly assigned treatment periods, separated by a minimum 14-day washout period per intervention.
Overall Number of Participants Analyzed 78 78
Mean (Standard Deviation)
Unit of Measure: ng/mL
157.0  (120.15) 309.3  (137.95)
3.Secondary Outcome
Title Focused Nasal Exam (Part A)
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population Cohort 1. (Accessed only for DZNS Arm)
Arm/Group Title DZNS - At 24 Hours Post-Dose - NONE DZNS - At 24 Hours Post-Dose - Grade 1a DZNS - At 24 Hours Post-Dose - Grade 1b DZNS - At 24 Hours Post-Dose - Grade 2 DZNS - At 24 Hours Post-Dose - Grade 3 DZNS - At 24 Hours Post-Dose - Grade 4 DZNS - At 24 Hours Post-Dose - Missing
Hide Arm/Group Description:

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

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

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

One dose of diazepam nasal spray is administered as two intranasal sprays; one in each nostril using a nasal spray device.

diazepam nasal spray

Overall Number of Participants Analyzed 78 78 78 78 78 78 78
Measure Type: Count of Participants
Unit of Measure: Participants
Nasal Irritation at Baseline - NONE
64
  82.1%
6
   7.7%
0
   0.0%
1
   1.3%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1a
1
   1.3%
3
   3.8%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1b
0
   0.0%
0
   0.0%
2
   2.6%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 3
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.3%
0
   0.0%
0
   0.0%
4.Secondary Outcome
Title Focused Nasal Exam (Part B)
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety population / Cohort 1. (Accessed only for DZNS Arm)
Arm/Group Title DZNS - At 24 Hours Post-Dose None DZNS - At 24 Hours Post-Dose Mild DZNS - At 24 Hours Post-Dose Moderate DZNS - At 24 Hours Post-Dose Severe DZNS - At 24 Hours Post-Dose Missing
Hide Arm/Group Description:

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

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

One dose of diazepam nasal spray is administered as two intranasal sprays; one in each nostril using a nasal spray device.

diazepam nasal spray

Overall Number of Participants Analyzed 78 78 78 78 78
Measure Type: Count of Participants
Unit of Measure: Participants
At Baseline: Mucosal Edema-None
70
  89.7%
3
   3.8%
0
   0.0%
0
   0.0%
0
   0.0%
Mucosal Edema - Mild
1
   1.3%
3
   3.8%
0
   0.0%
0
   0.0%
0
   0.0%
Mucosal Edema - Moderate
0
   0.0%
1
   1.3%
0
   0.0%
0
   0.0%
0
   0.0%
At Baseline: Nasal Discharge - None
67
  85.9%
7
   9.0%
1
   1.3%
0
   0.0%
0
   0.0%
Nasal Discharge - Mild
1
   1.3%
1
   1.3%
0
   0.0%
0
   0.0%
0
   0.0%
Nasal Discharge - Moderate
0
   0.0%
1
   1.3%
0
   0.0%
0
   0.0%
0
   0.0%
At Baseline: Mucosal Erythema - None
67
  85.9%
6
   7.7%
0
   0.0%
0
   0.0%
0
   0.0%
Mucosal Edrythema - Mild
0
   0.0%
5
   6.4%
0
   0.0%
0
   0.0%
0
   0.0%
At Baseline: Mucosal Bleeding/Epistaxis - None
76
  97.4%
1
   1.3%
0
   0.0%
0
   0.0%
0
   0.0%
Mucosal Bleeding/Epistaxis - Mild
1
   1.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
At Baseline: Crusting of Mucosa - None
77
  98.7%
1
   1.3%
0
   0.0%
0
   0.0%
0
   0.0%
5.Secondary Outcome
Title Smell Identification Test (SIT)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population / Cohort 1. (Accessed only for DZNS Arm)
Arm/Group Title At Follow-Up Visit - Normosmia At Follow-Up Visit - Mild Microsmia At Follow-Up Visit - Moderate Microsmia At Follow-Up Visit - Severe Microsmia At Follow-Up Visit - Anosmia At Follow-Up Visit - Probable Malingering At Follow-Up Visit - Missing
Hide Arm/Group Description:
Shift in SIT Scores in Cohort 1 from Treatment Period 1 (Prior to Dosing) to Follow-up Visit
Shift in SIT Scores in Cohort 1 from Treatment Period 1 (Prior to Dosing) to Follow-up Visit
Shift in SIT Scores in Cohort 1 from Treatment Period 1 (Prior to Dosing) to Follow-up Visit
Shift in SIT Scores in Cohort 1 from Treatment Period 1 (Prior to Dosing) to Follow-up Visit
Shift in SIT Scores in Cohort 1 from Treatment Period 1 (Prior to Dosing) to Follow-up Visit
Shift in SIT Scores in Cohort 1 from Treatment Period 1 (Prior to Dosing) to Follow-up Visit
Shift in SIT Scores in Cohort 1 from Treatment Period 1 (Prior to Dosing) to Follow-up Visit
Overall Number of Participants Analyzed 78 78 78 78 78 78 78
Measure Type: Count of Participants
Unit of Measure: Participants
At BASELINE: Normosmia
19
  24.4%
10
  12.8%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.3%
Mild Microsmia
2
   2.6%
10
  12.8%
5
   6.4%
1
   1.3%
0
   0.0%
0
   0.0%
0
   0.0%
Moderate Microsmia
2
   2.6%
3
   3.8%
3
   3.8%
6
   7.7%
1
   1.3%
0
   0.0%
0
   0.0%
Severe Microsmia
0
   0.0%
1
   1.3%
1
   1.3%
4
   5.1%
1
   1.3%
0
   0.0%
0
   0.0%
Anosmia
0
   0.0%
0
   0.0%
0
   0.0%
2
   2.6%
3
   3.8%
0
   0.0%
1
   1.3%
Probable Malingering
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Missing
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   2.6%
6.Secondary Outcome
Title Taste Change Questionnaire
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population / Cohort 1. (Accessed only for DZNS Arm)
Arm/Group Title Taste Change by Intensity in Cohort 1
Hide Arm/Group Description:
Questionnaire for taste change associated with diazepam nasal spray dosing.
Overall Number of Participants Analyzed 78
Mean (Standard Deviation)
Unit of Measure: units on a scale
5 mins Post-Dose 6.5  (3.57)
15 mins Post-Dose 4.6  (3.09)
30 mins Post Dose 2.8  (2.75)
1 hr Post Dose 1.0  (1.45)
2 hrs Post-Dose 0.3  (0.48)
4 hrs Post-Dose 0.1  (0.36)
8 hrs Post-Dose 0.0  (0.0)
12 hrs Post-Dose 0.0  (0.0)
24 hrs Post-Dose 0.0  (0.0)
Time Frame 31 Days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Diazepam Nasal Spray Diazepam Rectal Gel
Hide Arm/Group Description

One dose of diazepam nasal spray is administered as two intranasal sprays; one in each nostril using a nasal spray device.

Diazepam Nasal Spray

A single rectal dose of diazepam will be administered to subjects according to the Diastat prescribing information.

Diazepam Rectal Gel

All-Cause Mortality
Diazepam Nasal Spray Diazepam Rectal Gel
Affected / at Risk (%) Affected / at Risk (%)
Total   0/78 (0.00%)   0/78 (0.00%) 
Hide Serious Adverse Events
Diazepam Nasal Spray Diazepam Rectal Gel
Affected / at Risk (%) Affected / at Risk (%)
Total   0/78 (0.00%)   0/78 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Diazepam Nasal Spray Diazepam Rectal Gel
Affected / at Risk (%) Affected / at Risk (%)
Total   60/78 (76.92%)   20/78 (25.64%) 
Gastrointestinal disorders     
Abdominal Pain   0/78 (0.00%)  1/78 (1.28%) 
Anorectal discomfort   0/78 (0.00%)  1/78 (1.28%) 
Dysphagia   1/78 (1.28%)  0/78 (0.00%) 
Oral dysesthesia   1/78 (1.28%)  0/78 (0.00%) 
General disorders     
Nasal Discomfort   30/78 (38.46%)  3/78 (3.85%) 
Dysgeusia   25/78 (32.05%)  0/78 (0.00%) 
Lacrimation Increased   22/78 (28.21%)  0/78 (0.00%) 
Nasal Mucosal Disorder   10/78 (12.82%)  2/78 (2.56%) 
Rhinorrhea   10/78 (12.82%)  1/78 (1.28%) 
Edema Mucosal   8/78 (10.26%)  1/78 (1.28%) 
Throat irritation   9/78 (11.54%)  0/78 (0.00%) 
Feeling Hot   1/78 (1.28%)  0/78 (0.00%) 
Mucosal erosion   1/78 (1.28%)  0/78 (0.00%) 
Pyrexia   1/78 (1.28%)  0/78 (0.00%) 
Secretion discharge   1/78 (1.28%)  0/78 (0.00%) 
Infections and infestations     
Gastroenteritis viral   0/78 (0.00%)  1/78 (1.28%) 
Tonsillitis   0/78 (0.00%)  1/78 (1.28%) 
Investigations     
White blood cell count   0/78 (0.00%)  1/78 (1.28%) 
Musculoskeletal and connective tissue disorders     
Musculoskeletal stiffness   1/78 (1.28%)  0/78 (0.00%) 
Nervous system disorders     
Somnolence   4/78 (5.13%)  5/78 (6.41%) 
Headache   4/78 (5.13%)  1/78 (1.28%) 
Aura   0/78 (0.00%)  1/78 (1.28%) 
Burning sensation   1/78 (1.28%)  0/78 (0.00%) 
Dizziness   0/78 (0.00%)  1/78 (1.28%) 
Paresthesia   1/78 (1.28%)  0/78 (0.00%) 
Parosmia   1/78 (1.28%)  0/78 (0.00%) 
Sinus headache   1/78 (1.28%)  0/78 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Oropharyngeal Pain   4/78 (5.13%)  0/78 (0.00%) 
Rhinalgia   4/78 (5.13%)  0/78 (0.00%) 
Epistaxis   3/78 (3.85%)  1/78 (1.28%) 
Nasal congestion   3/78 (3.85%)  0/78 (0.00%) 
Cough   2/78 (2.56%)  0/78 (0.00%) 
Sneezing   2/78 (2.56%)  0/78 (0.00%) 
Hiccups   0/78 (0.00%)  1/78 (1.28%) 
Skin and subcutaneous tissue disorders     
Acne   0/78 (0.00%)  1/78 (1.28%) 
Hyperhidrosis   1/78 (1.28%)  0/78 (0.00%) 
Skin irritation   1/78 (1.28%)  0/78 (0.00%) 
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Lee Min Jae, Associate Manager
Organization: SK Bio-pharmaceuticals Co, Ltd
EMail: minj.lee@sk.com
Layout table for additonal information
Responsible Party: Acorda Therapeutics
ClinicalTrials.gov Identifier: NCT02474407    
Other Study ID Numbers: DZNS-EP-1019
First Submitted: June 15, 2015
First Posted: June 17, 2015
Results First Submitted: November 8, 2017
Results First Posted: October 16, 2018
Last Update Posted: October 16, 2018