Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 5 of 7 for:    aquestive

Study of Diazepam Buccal Film Administered in the Interictal and in the Ictal-Periictal States to Adults With Epilepsy

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: NCT03179891
Recruitment Status : Completed
First Posted : June 7, 2017
Results First Posted : September 18, 2020
Last Update Posted : September 18, 2020
Sponsor:
Collaborators:
inVentiv Health Clinical
Covance
Information provided by (Responsible Party):
Aquestive Therapeutics

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Epilepsy
Intervention Drug: Diazepam Buccal Film 12.5 mg
Enrollment 35
Recruitment Details Planned enrollment was 40 adult male and female subjects with a clinical diagnosis of epilepsy requiring admission to an epilepsy monitoring unit, a general clinical research center, or similar facility for evaluation of seizures. A minimum of 30 subjects was expected to complete the study.
Pre-assignment Details A total of 35 subjects were enrolled to receive a 12.5-mg dose of study drug during both the interictal and the ictal/peri-ictal period which occurred in either order as determined by seizure occurrence.
Arm/Group Title Interictal State First, Then Ictal/Peri-ictal State Ictal/Peri-Ictal State First, Then Interictal State
Hide Arm/Group Description Subjects received DBF 12.5 mg during the Interical State first and then during the Ictal/Peri-ictal State with at least 14 days washout between the 2 periods. Subjects received DBF 12.5 mg during the ictal/peri-ictal state first and then during the interictal state with at least 14 days washout between the 2 periods.
Period Title: First Intervention
Started 13 22
Completed 11 20
Not Completed 2 2
Reason Not Completed
Withdrawal by Subject             1             1
Unspecified reason             1             0
Protocol Violation             0             1
Period Title: Second Intervention (After 14 Days)
Started 11 20
Completed 11 20
Not Completed 0 0
Arm/Group Title Adult Subjects With Epilepsy
Hide Arm/Group Description Adult subjects with epilepsy admitted to an Epilepsy Monitoring Unit to receive a single 12.5 mg DBF dose during the Ictal Phase and during the Interictal/Peri-ictal Phase with at least 14 days between the 2 periods
Overall Number of Baseline Participants 35
Hide Baseline Analysis Population Description
Thirty-five subjects were enrolled to receive DBF 12.5 mg in both Interictal and Peri-ictal period with order determined by seizure occurrence. Four subjects withdrew after receiving their first dose; 2 subjects in the Interictal Period and 2 subjects in the Ictal/peri-ictal period.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 35 participants
<=18 years
0
   0.0%
Between 18 and 65 years
29
  82.9%
>=65 years
6
  17.1%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 35 participants
Female
18
  51.4%
Male
17
  48.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 35 participants
Hispanic or Latino
9
  25.7%
Not Hispanic or Latino
26
  74.3%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 35 participants
American Indian or Alaska Native
2
   5.7%
Asian
1
   2.9%
Native Hawaiian or Other Pacific Islander
6
  17.1%
Black or African American
5
  14.3%
White
19
  54.3%
More than one race
0
   0.0%
Unknown or Not Reported
2
   5.7%
Region of Enrollment   [1] 
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 35 participants
35
[1]
Measure Analysis Population Description: Thirty-five adult subjects with epilepsy received at least 1 dose of study drug and were included in the analysis of safety.
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 35 participants
165.64  (10.81)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 35 participants
79.24  (19.58)
BMI  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 35 participants
27.84  (7.01)
1.Primary Outcome
Title Tmax Pharmacokinetic EndPoints
Hide Description Observed time to reach maximum drug concentration (Tmax)
Time Frame -2 to 0, 0.25, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 192, 240 hours
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic analysis set comprised only those subjects who contributed a valid pharmacokinetic profile for the given analysis and whose predose concentration of the relevant analyte did not exceed 5% of the subsequent Cmax.
Arm/Group Title Interictal State Ictal/Peri-ictal State
Hide Arm/Group Description:

Single 12.5-mg dose of Diazepam Buccal Film administered during the interictal state

Adult subjects with epilepsy

Single 12.5-mg dose of Diazepam Buccal Film administered during the ictal/peri-ictal state

Adult subjects with epilepsy

Overall Number of Participants Analyzed 32 24
Median (Full Range)
Unit of Measure: hours
1.000
(0.249 to 4.017)
0.525
(0.250 to 2.033)
2.Primary Outcome
Title Cmax Pharmacokinetic EndPoints
Hide Description Observed Peak Drug Concentration (Cmax)
Time Frame -2 to 0, 0.25, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 192, 240 hours
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic analysis set comprised only those subjects who contributed a valid pharmacokinetic profile for the given analysis and whose predose concentration of the relevant analyte did not exceed 5% of the subsequent Cmax.
Arm/Group Title Interictal State Ictal/Peri-ictal State
Hide Arm/Group Description:

Single 12.5 mg dose of Diazepam Buccal Film administered during the interictal state

Adult subjects with epilepsy

Single 12.5 mg dose of Diazepam Buccal Film administered during the ictal/peri-ictal state.

Adult subjects with epilepsy

Overall Number of Participants Analyzed 32 24
Mean (Standard Deviation)
Unit of Measure: ng/mL
230.32  (89.00) 209.49  (120.18)
3.Primary Outcome
Title Area Under the Plasma Concentration Curve Pharmacokinetic EndPoints
Hide Description Area under the Plasma Concentration -time curve from time zero until the last measured time (AUC0-t)
Time Frame -2 to 0, 0.25, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 192, 240 hours
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic analysis set comprised only those subjects who contributed a valid pharmacokinetic profile for the given analysis and whose predose concentration of the relevant analyte did not exceed 5% of the subsequent Cmax.
Arm/Group Title Interictal State Ictal/Peri-ictal State
Hide Arm/Group Description:

Single 12.5-mg dose of Diazepam Buccal Film administered during the interictal state

Adult subjects with epilepsy

Single 12.5-mg dose of Diazepam Buccal Film administered during the ictal/peri-ictal state

Adult subjects with epilepsy

Overall Number of Participants Analyzed 32 24
Mean (Standard Deviation)
Unit of Measure: h*ng/mL
560.18  (219.70) 498.78  (319.09)
4.Secondary Outcome
Title Usability Endpoint - Successful Insertion/Placement of the Diazepam Buccal Film (DBF) on First Attempt
Hide Description

Number of subjects with unsuccessful insertion/placement of the DBF on first attempt at administration Number of subjects with successful insertion/placement of the DBF on first attempt at administration

Placement is judged to be successful when film adheres to the center of buccal mucosa of either right or left cheek.

Unsuccessful placements were followed by a subsequent successful insertion/placement of DBF

Time Frame Subject was observed for 15 minutes after initial film placement/adhesion
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population comprising all subjects who received at least 1 dose of study drug (Diazepam Buccal Film).
Arm/Group Title Interictal State Ictal/Peri-ictal State
Hide Arm/Group Description:

Single 12.5-mg dose of Diazepam Buccal Film administered during the interictal state.

Adult subjects with epilepsy

Single 12.5-mg dose of Diazepam Buccal Film administered during the ictal/peri-ictal state

Adult subjects with epilepsy

Overall Number of Participants Analyzed 33 33
Measure Type: Count of Participants
Unit of Measure: Participants
Unsuccessful insertion/placement
0
   0.0%
2
   6.1%
Successful insertion/placement
33
 100.0%
31
  93.9%
5.Secondary Outcome
Title Usability Endpoint: Swallowing the Film Before Complete Disintegration/Dissolution
Hide Description

Was the film noted to have been swallowed by the subject ? Yes No

Subjects were instructed to swallow any remnants of film still present in oral cavity 15 minutes after initial film placement.

Results include subjects who swallowed film at any point during the 15 minutes immediately after initial film placement.

Time Frame Subject was observed for 15 minutes immediately following DBF placement/adhesion
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population comprising all subjects who received at least 1 dose of study drug (Diazepam Buccal Film).
Arm/Group Title Interictal State Ictal/Peri-ictal State
Hide Arm/Group Description:

Single 12.5-mg dose of Diazepam Buccal Film administered during the interictal state.

Adult subjects with epilepsy

Single 12.5-mg dose of Diazepam Buccal Film administered during the ictal/peri-ictal state

Adult subjects with epilepsy

Overall Number of Participants Analyzed 33 33
Measure Type: Count of Participants
Unit of Measure: Participants
Yes-DBF was Swallowed
4
  12.1%
2
   6.1%
No-DBF was not Swallowed
29
  87.9%
31
  93.9%
6.Secondary Outcome
Title Usability Endpoint: Retention of Diazepam Buccal Film (DBF) From Placement to Complete Disintegration
Hide Description Was the DBF spit out or blown out by the subject after placement on buccal mucosa or did the subject chew, talk, or move the DBF prior to complete disintegration/dissolution? Yes No
Time Frame Subject was observed for 15 minutes immediately following DBF placement/adhesion
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population comprising all subjects who received at least 1 dose of study drug (Diazepam Buccal Film).
Arm/Group Title Interictal State Ictal/Peri-ictal State
Hide Arm/Group Description:

Single 12.5-mg dose of Diazepam Buccal Film administered during the interictal state.

Adult subjects with epilepsy

Single 12.5-mg dose of Diazepam Buccal Film administered during the ictal/peri-ictal state

Adult subjects with epilepsy

Overall Number of Participants Analyzed 33 33
Measure Type: Count of Participants
Unit of Measure: Participants
Yes-DBF was spit out/blown out
0
   0.0%
3
   9.1%
No-DBF was not spit out/blown out
33
 100.0%
30
  90.9%
7.Secondary Outcome
Title Usability Endpoint: Exit of Saliva During the Time the Diazepam Buccal Film (DBF) Was Adhered to Buccal Mucosa
Hide Description The observer documented if any saliva was seen to exit the mouth during the time the DBF was adhered to buccal mucosa
Time Frame Subject was observed for 15 minutes immediately following DBF placement/adhesion
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population comprising all subjects who received at least 1 dose of study drug (Diazepam Buccal Film).
Arm/Group Title Interictal State Ictal/Peri-ictal State
Hide Arm/Group Description:

Single 12.5-mg dose of Diazepam Buccal Film administered during the interictal state.

Adult subjects with epilepsy

Single 12.5-mg dose of Diazepam Buccal Film administered during the ictal/peri-ictal state

Adult subjects with epilepsy

Overall Number of Participants Analyzed 33 33
Measure Type: Count of Participants
Unit of Measure: Participants
Yes, saliva exited the mouth
0
   0.0%
2
   6.1%
No, saliva did not exit mouth
33
 100.0%
31
  93.9%
8.Secondary Outcome
Title Usability Endpoint: Amount of Saliva That Exited the Mouth After Film Placement
Hide Description If Yes - saliva exited the mouth during the time, estimate in milliliters of the amount of saliva that exited the mouth after DBF placement on the buccal surface
Time Frame Subject was observed for 15 minutes immediately following DBF placement/adhesion
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population comprising all subjects who received at least 1 dose of study drug (Diazepam Buccal Film).
Arm/Group Title Interictal State Ictal/Peri-ictal State
Hide Arm/Group Description:

Single 12.5-mg dose of Diazepam Buccal Film administered during the interictal state.

Adult subjects with epilepsy

Single 12.5-mg dose of Diazepam Buccal Film administered during the ictal/peri-ictal state

Adult subjects with epilepsy

Overall Number of Participants Analyzed 33 33
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with 0 mL saliva exiting the mouth
33
 100.0%
31
  93.9%
Participants with 1 mL saliva exiting the mouth
0
   0.0%
1
   3.0%
Participants with 2 mL saliva exiting the mouth
0
   0.0%
1
   3.0%
Time Frame Adverse events were collected throughout the course of the study for each subject (approximately 1 month for each subject - beginning with the first DBF dose until 14 ± 2 days following the second DBF dose).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Interictal State (Period A) Ictal/Peri-ictal State (Period B)
Hide Arm/Group Description

Single 12.5-mg dose of Diazepam Buccal Film administered during the interictal state.

Adult subjects with epilepsy

Single 12.5-mg dose of Diazepam Buccal Film administered during the ictal/peri-ictal state.

Adult subjects with epilepsy

All-Cause Mortality
Interictal State (Period A) Ictal/Peri-ictal State (Period B)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/33 (0.00%)      0/33 (0.00%)    
Hide Serious Adverse Events
Interictal State (Period A) Ictal/Peri-ictal State (Period B)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/33 (0.00%)      1/33 (3.03%)    
Nervous system disorders     
HOSPITALIZATION DUE TO SEIZURE CLUSTER  1  0/33 (0.00%)  0 1/33 (3.03%)  1
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Interictal State (Period A) Ictal/Peri-ictal State (Period B)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   12/33 (36.36%)      14/33 (42.42%)    
Gastrointestinal disorders     
Diarrhoea  1  0/33 (0.00%)  0 1/33 (3.03%)  1
Nervous system disorders     
Complex Partial Seizures  1  9/33 (27.27%)  9 14/33 (42.42%)  14
Headache  1  0/33 (0.00%)  0 3/33 (9.09%)  3
Generalized tonic-clonic seizure  1  1/33 (3.03%)  6 1/33 (3.03%)  3
Seizure  1  1/33 (3.03%)  2 1/33 (3.03%)  4
Somnolence  1  2/33 (6.06%)  3 0/33 (0.00%)  0
Seizure cluster  1  0/33 (0.00%)  0 1/33 (3.03%)  1
1
Term from vocabulary, MedDRA 20.0
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.
Trial results were included as confidential information and required written sponsor approval.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Director of Clinical Operations
Organization: Aquestive Therapeutics
Phone: 908-941-1900
EMail: clinicaltrials@aquestive.com
Layout table for additonal information
Responsible Party: Aquestive Therapeutics
ClinicalTrials.gov Identifier: NCT03179891    
Other Study ID Numbers: 160326
First Submitted: May 26, 2017
First Posted: June 7, 2017
Results First Submitted: June 24, 2020
Results First Posted: September 18, 2020
Last Update Posted: September 18, 2020