Trial Outcomes & Findings for Study of Diazepam Buccal Film Administered in the Interictal and in the Ictal-Periictal States to Adults With Epilepsy (NCT NCT03179891)
NCT ID: NCT03179891
Last Updated: 2020-09-18
Results Overview
Observed time to reach maximum drug concentration (Tmax)
COMPLETED
PHASE2
35 participants
-2 to 0, 0.25, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 192, 240 hours
2020-09-18
Participant Flow
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.
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.
Participant milestones
| Measure |
Interictal State First, Then Ictal/Peri-ictal State
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.
|
Ictal/Peri-Ictal State First, Then Interictal State
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.
|
|---|---|---|
|
First Intervention
STARTED
|
13
|
22
|
|
First Intervention
COMPLETED
|
11
|
20
|
|
First Intervention
NOT COMPLETED
|
2
|
2
|
|
Second Intervention (After 14 Days)
STARTED
|
11
|
20
|
|
Second Intervention (After 14 Days)
COMPLETED
|
11
|
20
|
|
Second Intervention (After 14 Days)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Interictal State First, Then Ictal/Peri-ictal State
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.
|
Ictal/Peri-Ictal State First, Then Interictal State
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.
|
|---|---|---|
|
First Intervention
Withdrawal by Subject
|
1
|
1
|
|
First Intervention
Unspecified reason
|
1
|
0
|
|
First Intervention
Protocol Violation
|
0
|
1
|
Baseline Characteristics
Thirty-five adult subjects with epilepsy received at least 1 dose of study drug and were included in the analysis of safety.
Baseline characteristics by cohort
| Measure |
Adult Subjects With Epilepsy
n=35 Participants
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
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
29 Participants
n=99 Participants
|
|
Age, Categorical
>=65 years
|
6 Participants
n=99 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
9 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
26 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
2 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
6 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
19 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
35 participants
n=99 Participants • Thirty-five adult subjects with epilepsy received at least 1 dose of study drug and were included in the analysis of safety.
|
|
Height
|
165.64 cm
STANDARD_DEVIATION 10.81 • n=99 Participants
|
|
Weight
|
79.24 kg
STANDARD_DEVIATION 19.58 • n=99 Participants
|
|
BMI
|
27.84 kg/m^2
STANDARD_DEVIATION 7.01 • n=99 Participants
|
PRIMARY outcome
Timeframe: -2 to 0, 0.25, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 192, 240 hoursPopulation: 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.
Observed time to reach maximum drug concentration (Tmax)
Outcome measures
| Measure |
Interictal State
n=32 Participants
Single 12.5-mg dose of Diazepam Buccal Film administered during the interictal state
Adult subjects with epilepsy
|
Ictal/Peri-ictal State
n=24 Participants
Single 12.5-mg dose of Diazepam Buccal Film administered during the ictal/peri-ictal state
Adult subjects with epilepsy
|
|---|---|---|
|
Tmax Pharmacokinetic EndPoints
|
1.000 hours
Interval 0.249 to 4.017
|
0.525 hours
Interval 0.25 to 2.033
|
PRIMARY outcome
Timeframe: -2 to 0, 0.25, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 192, 240 hoursPopulation: 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.
Observed Peak Drug Concentration (Cmax)
Outcome measures
| Measure |
Interictal State
n=32 Participants
Single 12.5-mg dose of Diazepam Buccal Film administered during the interictal state
Adult subjects with epilepsy
|
Ictal/Peri-ictal State
n=24 Participants
Single 12.5-mg dose of Diazepam Buccal Film administered during the ictal/peri-ictal state
Adult subjects with epilepsy
|
|---|---|---|
|
Cmax Pharmacokinetic EndPoints
|
230.32 ng/mL
Standard Deviation 89.00
|
209.49 ng/mL
Standard Deviation 120.18
|
PRIMARY outcome
Timeframe: -2 to 0, 0.25, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 192, 240 hoursPopulation: 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.
Area under the Plasma Concentration -time curve from time zero until the last measured time (AUC0-t)
Outcome measures
| Measure |
Interictal State
n=32 Participants
Single 12.5-mg dose of Diazepam Buccal Film administered during the interictal state
Adult subjects with epilepsy
|
Ictal/Peri-ictal State
n=24 Participants
Single 12.5-mg dose of Diazepam Buccal Film administered during the ictal/peri-ictal state
Adult subjects with epilepsy
|
|---|---|---|
|
Area Under the Plasma Concentration Curve Pharmacokinetic EndPoints
|
560.18 h*ng/mL
Standard Deviation 219.70
|
498.78 h*ng/mL
Standard Deviation 319.09
|
SECONDARY outcome
Timeframe: Subject was observed for 15 minutes after initial film placement/adhesionPopulation: Safety Population comprising all subjects who received at least 1 dose of study drug (Diazepam Buccal Film).
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
Outcome measures
| Measure |
Interictal State
n=33 Participants
Single 12.5-mg dose of Diazepam Buccal Film administered during the interictal state
Adult subjects with epilepsy
|
Ictal/Peri-ictal State
n=33 Participants
Single 12.5-mg dose of Diazepam Buccal Film administered during the ictal/peri-ictal state
Adult subjects with epilepsy
|
|---|---|---|
|
Usability Endpoint - Successful Insertion/Placement of the Diazepam Buccal Film (DBF) on First Attempt
Unsuccessful insertion/placement
|
0 Participants
|
2 Participants
|
|
Usability Endpoint - Successful Insertion/Placement of the Diazepam Buccal Film (DBF) on First Attempt
Successful insertion/placement
|
33 Participants
|
31 Participants
|
SECONDARY outcome
Timeframe: Subject was observed for 15 minutes immediately following DBF placement/adhesionPopulation: Safety Population comprising all subjects who received at least 1 dose of study drug (Diazepam Buccal Film).
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.
Outcome measures
| Measure |
Interictal State
n=33 Participants
Single 12.5-mg dose of Diazepam Buccal Film administered during the interictal state
Adult subjects with epilepsy
|
Ictal/Peri-ictal State
n=33 Participants
Single 12.5-mg dose of Diazepam Buccal Film administered during the ictal/peri-ictal state
Adult subjects with epilepsy
|
|---|---|---|
|
Usability Endpoint: Swallowing the Film Before Complete Disintegration/Dissolution
Yes-DBF was Swallowed
|
4 Participants
|
2 Participants
|
|
Usability Endpoint: Swallowing the Film Before Complete Disintegration/Dissolution
No-DBF was not Swallowed
|
29 Participants
|
31 Participants
|
SECONDARY outcome
Timeframe: Subject was observed for 15 minutes immediately following DBF placement/adhesionPopulation: Safety Population comprising all subjects who received at least 1 dose of study drug (Diazepam Buccal Film).
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
Outcome measures
| Measure |
Interictal State
n=33 Participants
Single 12.5-mg dose of Diazepam Buccal Film administered during the interictal state
Adult subjects with epilepsy
|
Ictal/Peri-ictal State
n=33 Participants
Single 12.5-mg dose of Diazepam Buccal Film administered during the ictal/peri-ictal state
Adult subjects with epilepsy
|
|---|---|---|
|
Usability Endpoint: Retention of Diazepam Buccal Film (DBF) From Placement to Complete Disintegration
Yes-DBF was spit out/blown out
|
0 Participants
|
3 Participants
|
|
Usability Endpoint: Retention of Diazepam Buccal Film (DBF) From Placement to Complete Disintegration
No-DBF was not spit out/blown out
|
33 Participants
|
30 Participants
|
SECONDARY outcome
Timeframe: Subject was observed for 15 minutes immediately following DBF placement/adhesionPopulation: Safety Population comprising all subjects who received at least 1 dose of study drug (Diazepam Buccal Film).
The observer documented if any saliva was seen to exit the mouth during the time the DBF was adhered to buccal mucosa
Outcome measures
| Measure |
Interictal State
n=33 Participants
Single 12.5-mg dose of Diazepam Buccal Film administered during the interictal state
Adult subjects with epilepsy
|
Ictal/Peri-ictal State
n=33 Participants
Single 12.5-mg dose of Diazepam Buccal Film administered during the ictal/peri-ictal state
Adult subjects with epilepsy
|
|---|---|---|
|
Usability Endpoint: Exit of Saliva During the Time the Diazepam Buccal Film (DBF) Was Adhered to Buccal Mucosa
Yes, saliva exited the mouth
|
0 Participants
|
2 Participants
|
|
Usability Endpoint: Exit of Saliva During the Time the Diazepam Buccal Film (DBF) Was Adhered to Buccal Mucosa
No, saliva did not exit mouth
|
33 Participants
|
31 Participants
|
SECONDARY outcome
Timeframe: Subject was observed for 15 minutes immediately following DBF placement/adhesionPopulation: Safety Population comprising all subjects who received at least 1 dose of study drug (Diazepam Buccal Film).
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
Outcome measures
| Measure |
Interictal State
n=33 Participants
Single 12.5-mg dose of Diazepam Buccal Film administered during the interictal state
Adult subjects with epilepsy
|
Ictal/Peri-ictal State
n=33 Participants
Single 12.5-mg dose of Diazepam Buccal Film administered during the ictal/peri-ictal state
Adult subjects with epilepsy
|
|---|---|---|
|
Usability Endpoint: Amount of Saliva That Exited the Mouth After Film Placement
Participants with 0 mL saliva exiting the mouth
|
33 Participants
|
31 Participants
|
|
Usability Endpoint: Amount of Saliva That Exited the Mouth After Film Placement
Participants with 1 mL saliva exiting the mouth
|
0 Participants
|
1 Participants
|
|
Usability Endpoint: Amount of Saliva That Exited the Mouth After Film Placement
Participants with 2 mL saliva exiting the mouth
|
0 Participants
|
1 Participants
|
Adverse Events
Interictal State (Period A)
Ictal/Peri-ictal State (Period B)
Serious adverse events
| Measure |
Interictal State (Period A)
n=33 participants at risk
Single 12.5-mg dose of Diazepam Buccal Film administered during the interictal state.
Adult subjects with epilepsy
|
Ictal/Peri-ictal State (Period B)
n=33 participants at risk
Single 12.5-mg dose of Diazepam Buccal Film administered during the ictal/peri-ictal state.
Adult subjects with epilepsy
|
|---|---|---|
|
Nervous system disorders
HOSPITALIZATION DUE TO SEIZURE CLUSTER
|
0.00%
0/33 • 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).
|
3.0%
1/33 • Number of events 1 • 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).
|
Other adverse events
| Measure |
Interictal State (Period A)
n=33 participants at risk
Single 12.5-mg dose of Diazepam Buccal Film administered during the interictal state.
Adult subjects with epilepsy
|
Ictal/Peri-ictal State (Period B)
n=33 participants at risk
Single 12.5-mg dose of Diazepam Buccal Film administered during the ictal/peri-ictal state.
Adult subjects with epilepsy
|
|---|---|---|
|
Nervous system disorders
Complex Partial Seizures
|
27.3%
9/33 • Number of events 9 • 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).
|
42.4%
14/33 • Number of events 14 • 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).
|
|
Nervous system disorders
Headache
|
0.00%
0/33 • 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).
|
9.1%
3/33 • Number of events 3 • 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).
|
|
Nervous system disorders
Generalized tonic-clonic seizure
|
3.0%
1/33 • Number of events 6 • 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).
|
3.0%
1/33 • Number of events 3 • 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).
|
|
Nervous system disorders
Seizure
|
3.0%
1/33 • Number of events 2 • 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).
|
3.0%
1/33 • Number of events 4 • 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).
|
|
Nervous system disorders
Somnolence
|
6.1%
2/33 • Number of events 3 • 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).
|
0.00%
0/33 • 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).
|
|
Nervous system disorders
Seizure cluster
|
0.00%
0/33 • 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).
|
3.0%
1/33 • Number of events 1 • 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).
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/33 • 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).
|
3.0%
1/33 • Number of events 1 • 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).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Trial results were included as confidential information and required written sponsor approval.
- Publication restrictions are in place
Restriction type: OTHER