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

• Sponsor: Aquestive Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03179891
• Collaborator: inVentiv Health Clinical (Other), Covance (Industry)
• Enrollment: 35
• Locations: 11
• Arms: 2
• Actual Duration (Months): 18.9
• Patients Per Site: 3.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This Phase 2 open-label, two-way study was conducted in adult subjects with epilepsy who were on stable regimens of anti-epileptic drugs (AEDs) and who were admitted to an Epilepsy Monitoring Unit (EMU), General Clinical Research Center (GCRC), or similar facility for evaluation of their seizures. All subjects received a single DBF 12.5 mg dose during the Interictal State and a single DBF 12.5 mg dose during the Ictal/peri-ictal state with at least 14 days washout between the 2 doses.

Condition or Disease	Intervention/Treatment	Phase
Epilepsy	Drug: Diazepam Buccal Film 12.5 mg	Phase 2

Detailed Description

This was a Phase 2 multicenter, open-label, two-way study conducted in adult subjects to assess the bioavailability, pharmacokinetics, and safety of DBF during the Interictal Period and during the Ictal/peri-ictal Period, with a minimum of 14 days of washout between periods. Subjects had a clinical diagnosis of epilepsy (with generalized tonic-clonic seizures or focal seizures with impaired awareness) who were on stable regimens of anti-epileptic drugs and were scheduled for admission to an EMU, GCRC, or similar facility for evaluation.

All subjects were to receive a single 12.5-mg dose of study drug, without regard to meals, during both Interictal Period and Ictal/peri-ictal Period. The treatment was identical for both periods. Treatment sequence was not randomized. The interictal period and ictal/peri-ictal could occur in either order as determined by seizure occurrence.

Interictal Period: Subjects were considered to be in an interictal state if an interval of at least 3 hours had elapsed since any clinically observable postictal signs or symptoms (from the last observed seizure) and the subject had been seizure-free over this period. Subjects on electroencephalogram (EEG) video monitoring were to be considered to be in an interictal state if an interval of at least 3 hours had elapsed since there were any postictal electrical findings on EEG.

Ictal/peri-ictal Period: For the purposes of this study, the ictal state was defined as an ongoing clinically observable seizure or seizure activity as verified via EEG. The periictal state was defined clinically as the subject's immediate postictal state following a generalized tonic-clonic (GTC) seizure or focal seizure with impaired awareness, and within 5 minutes following the last clonic jerk. For subjects on EEG video monitoring, the periictal state was to be defined as less than 5 minutes after cessation of seizure activity as verified via EEG.

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: This was a multicenter, open-label study comprised of 2 treatment periods with a minimum 14 days washout between the 2 treatment periods.This was a multicenter, open-label study comprised of 2 treatment periods with a minimum 14 days washout between the 2 treatment periods.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Open Label, Crossover Study to Assess the Pharmacokinetics and Safety of Diazepam Buccal Soluble Film (DBSF) in Adult Subjects With Epilepsy
• Actual Study Start Date: May 25, 2017
• Actual Primary Completion Date: Jul 25, 2018
• Actual Study Completion Date: Dec 21, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Interictal Period All subjects received 12.5 mg DBF during the interictal state.	Drug: Diazepam Buccal Film 12.5 mg; All subjects received a single dose of DBF 12.5 mg during the interictal state and during the ictal/peri-ictal state with at least 14 days washout between the 2 treatment periods; Other Names: DBF 12.5mg
Experimental: Ictal/Peri-ictal Period All subjects received 12.5 mg DBF during the ictal/peri-ictal state.	Drug: Diazepam Buccal Film 12.5 mg; All subjects received a single dose of DBF 12.5 mg during the interictal state and during the ictal/peri-ictal state with at least 14 days washout between the 2 treatment periods; Other Names: DBF 12.5mg

Outcome Measures

Primary Outcome Measures

1. Tmax Pharmacokinetic EndPoints [-2 to 0, 0.25, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 192, 240 hours]

   Observed time to reach maximum drug concentration (Tmax)

2. Cmax Pharmacokinetic EndPoints [-2 to 0, 0.25, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 192, 240 hours]

   Observed Peak Drug Concentration (Cmax)

3. Area Under the Plasma Concentration Curve Pharmacokinetic EndPoints [-2 to 0, 0.25, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 192, 240 hours]

   Area under the Plasma Concentration -time curve from time zero until the last measured time (AUC0-t)

Secondary Outcome Measures

1. Usability Endpoint - Successful Insertion/Placement of the Diazepam Buccal Film (DBF) on First Attempt [Subject was observed for 15 minutes after initial film placement/adhesion]

   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

2. Usability Endpoint: Swallowing the Film Before Complete Disintegration/Dissolution [Subject was observed for 15 minutes immediately following DBF placement/adhesion]

   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.

3. Usability Endpoint: Retention of Diazepam Buccal Film (DBF) From Placement to Complete Disintegration [Subject was observed for 15 minutes immediately following DBF placement/adhesion]

   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

4. Usability Endpoint: Exit of Saliva During the Time the Diazepam Buccal Film (DBF) Was Adhered to Buccal Mucosa [Subject was observed for 15 minutes immediately following DBF placement/adhesion]

   The observer documented if any saliva was seen to exit the mouth during the time the DBF was adhered to buccal mucosa

5. Usability Endpoint: Amount of Saliva That Exited the Mouth After Film Placement [Subject was observed for 15 minutes immediately following DBF placement/adhesion]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Potential subjects meeting all of the following criteria may be included in the study:

1. Subjects scheduled for admission to the institution's EMU, GCRC (General Clinical Research Center) or similar facility for evaluation within 28 days.

2. Male and female subjects between 18 to 65 years of age, inclusive.

3. Subjects having a body weight of ≥ 40 kg to 111 kg.

4. Subjects have a clinical diagnosis of epilepsy and are scheduled to be admitted to an Epilepsy Monitoring Unit (EMU) for extracranial video-Electroencephalogram (EEG) recording of a seizure event for evaluation of their epilepsy.

5. Subjects have an average frequency of > 1 seizure every 3 days or > 10 seizures / month as documented by seizure diaries dispensed at the Screening Visit and verified prior to initiation of Period A or Period B.

6. Female subjects have a negative serum pregnancy test at Screening. Female subjects of childbearing potential (i.e., not surgically sterile or 2 years postmenopausal) must have a negative pregnancy test at screening and a partner who is sterile, agree to abstinence, be practicing double barrier contraception or using an FDA approved contraceptive (e.g., licensed hormonal or barrier methods) for greater than 2 months prior to screening visit and commit to an acceptable form of birth control for the duration of the study and for 30 days after participation in the study.

7. Subjects are currently receiving at least one antiepileptic medication.

8. Subjects or subject's legally authorized representative (LAR) must be willing and able to complete informed consent/assent and HIPAA authorization.

9. Subjects must agree and must be willing to comply with all required study procedures while in the EMU or GCRC.

10. Ability to comprehend and be informed of the nature of the study, as assessed by the PI or Sub-Investigator.

11. Ability to consume standard meals.

12. Availability to volunteer for the entire study duration and willing to adhere to all protocol requirements.

Exclusion Criteria:

Potential subjects meeting any of the following criteria will be excluded:

1. Subjects having a progressive neurological disorder such as brain tumor, demyelinating disease, or degenerative central nervous system (CNS) disease that is likely to progress in the next 12 months.

2. Subjects having respiratory failure (or is at risk for respiratory failure) or other severe cardiorespiratory disease with New York Heart Association Class III or IV functional status, or requires supplemental oxygen.

3. Female subjects who are lactating or positive serum pregnancy test (ß-hCG) at screening for female subjects ≥12 years of age.

4. Subjects with severe psychiatric disease that in the Investigator's judgment would prevent the patient's successful completion of the study.

5. Subjects who have an episode of status epilepticus, as determined by the Principal Investigator/Sub-Investigator, at any time during Period B (EMU, GCRC or similar facility Visit

6. Subjects with known history or presence of any clinically significant hepatic (e.g. hepatic impairment), renal/genitourinary (renal impairment, kidney stones), psychiatric, dermatological or hematological disease or condition unless determined as not clinically significant by the Principal Investigator/Sub-Investigator and confirmed by Sponsor via written communication prior to subject enrollment.

7. Subjects with any clinically significant illness other than epilepsy within 30 days prior to first dosing, as determined by the Principal Investigator/Sub-Investigator.

8. Subjects with any significant physical or organ abnormality as determined by the Principal Investigator/Sub-Investigator.

9. Subjects with any significant lesion of the oral cavity or having oral prophylactic procedures within 30 days prior to first dosing.

10. Subjects with a QTc interval QTcF>450 msec for males and QTcF>470 msec for females on screening ECG, unless determined as not clinically significant by the Investigator.

11. Subjects with a positive test result for any of the following: drugs of abuse (amphetamines, cocaine, opiates, or phencyclidine), a positive breath alcohol test.

12. Subjects with a known history or presence of: a. Alcohol abuse or dependence within one year prior to first drug administration; b. Drug abuse or dependence; c. Hypersensitivity or idiosyncratic reaction to diazepam, its excipients, sodium phosphates; and/or related substances, e.g. benzodiazepines; d. Glaucoma (open or acute narrow angle); e. Severe allergic reactions (e.g. anaphylactic reactions, angioedema

13. Subjects who have participated in another clinical trial or who received an investigational drug within 30 days prior to first drug administration or 5 half-lives of the investigational drug-whichever is the longer period.

14. Blood or plasma donation within 30 days prior to Screening

15. Subjects not willing or unable to tolerate blood draws.

16. Subjects who have received any other dosage form of diazepam or benzodiazepines within 2 weeks prior to entering Period A or Period B.

17. Consumption of alcohol within 48 hours before dosing and food or beverages containing grapefruit, star fruit, Seville oranges, and/or pomelo or their derived products (e.g., fruit juice) within 10 days prior to first drug administration.

18. Use of any enzyme-modifying drugs, including strong inhibitors of cytochrome P450 (CYP) enzymes (e.g. cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem, or HIV antivirals) and strong inducers of CYP enzymes (e.g. glucocorticoids, St. John´s Wort, or rifampicin) in the previous 30 days before first drug administration [barbiturates, carbamazepine, and phenytoin are allowed since these are common AEDs (Anti-epileptic drugs)].

19. Use of any monoamine oxidase (MAO) inhibitors (e.g. phenelzine, tranylcypromine), phenothiazines (chlorpromazine) within 30 days prior to first drug administration.

20. Employee or immediate relative of an employee of the investigator, MonoSol Rx LLC, any of its affiliates or partners, or inVentiv Health.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Health Sciences Center	Tucson	Arizona	United States	85724-5023
2	Rancho Research Institute	Downey	California	United States	90242
3	Yale University School of Medicine-Comprehensive Epilepsy Center	New Haven	Connecticut	United States	06520-8018
4	Hawaii Pacific Neuroscience	Honolulu	Hawaii	United States	96817
5	Mid-Atlantic Epilepsy and Sleep Center	Bethesda	Maryland	United States	20817
6	Saint Peter's University Hospital	New Brunswick	New Jersey	United States	08901
7	University of Rochester Medical Center	Rochester	New York	United States	14642
8	Onsite Clinical Solutions LLC	Charlotte	North Carolina	United States	28203
9	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
10	Austin Epilepsy Care Center	Austin	Texas	United States	78758
11	Virginia Commonwealth University Medical Center	Richmond	Virginia	United States	23219

Sponsors and Collaborators

• Aquestive Therapeutics
• inVentiv Health Clinical
• Covance

Investigators

• Study Director: Gary Slatko, Aquestive Therapeutics

Study Documents (Full-Text)

• Study Protocol - Aug 4, 2017
• Statistical Analysis Plan - Sep 14, 2018

More Information

Publications

None provided.

• Responsible Party: Aquestive Therapeutics
• ClinicalTrials.gov Identifier: NCT03179891
• Other Study ID Numbers: 160326
• First Posted: Jun 7, 2017
• Last Update Posted: Sep 18, 2020
• Last Verified: Sep 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Aquestive Therapeutics: Interictal; Ictal/peri-ictal
• Additional relevant MeSH terms: Epilepsy; Diazepam

Study Results

Participant Flow

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 Detail	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
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
Period Title: First Intervention
STARTED	11	20
COMPLETED	11	20
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Adult Subjects With Epilepsy
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 Participants	35
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	29 82.9%
>=65 years	6 17.1%
Sex: Female, Male (Count of Participants)
Female	18 51.4%
Male	17 48.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	9 25.7%
Not Hispanic or Latino	26 74.3%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of 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%
Unknown or Not Reported	2 5.7%
Region of Enrollment (participants) [Number]
United States	35 100%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	165.64 (10.81)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	79.24 (19.58)
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	27.84 (7.01)

Outcome Measures

1. Primary Outcome

Title	Tmax Pharmacokinetic EndPoints
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

Outcome Measure Data

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
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
Measure Participants	32	24
Median (Full Range) [hours]	1.000	0.525

2. Primary Outcome

Title	Cmax Pharmacokinetic EndPoints
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

Outcome Measure Data

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
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
Measure Participants	32	24
Mean (Standard Deviation) [ng/mL]	230.32 (89.00)	209.49 (120.18)

3. Primary Outcome

Title	Area Under the Plasma Concentration Curve Pharmacokinetic EndPoints
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

Outcome Measure Data

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
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
Measure Participants	32	24
Mean (Standard Deviation) [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
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

Outcome Measure Data

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
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
Measure Participants	33	33
Unsuccessful insertion/placement	0 0%	2 NaN
Successful insertion/placement	33 94.3%	31 NaN

5. Secondary Outcome

Title	Usability Endpoint: Swallowing the Film Before Complete Disintegration/Dissolution
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

Outcome Measure Data

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
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
Measure Participants	33	33
Yes-DBF was Swallowed	4 11.4%	2 NaN
No-DBF was not Swallowed	29 82.9%	31 NaN

6. Secondary Outcome

Title	Usability Endpoint: Retention of Diazepam Buccal Film (DBF) From Placement to Complete Disintegration
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

Outcome Measure Data

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
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
Measure Participants	33	33
Yes-DBF was spit out/blown out	0 0%	3 NaN
No-DBF was not spit out/blown out	33 94.3%	30 NaN

7. Secondary Outcome

Title	Usability Endpoint: Exit of Saliva During the Time the Diazepam Buccal Film (DBF) Was Adhered to Buccal Mucosa
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

Outcome Measure Data

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
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
Measure Participants	33	33
Yes, saliva exited the mouth	0 0%	2 NaN
No, saliva did not exit mouth	33 94.3%	31 NaN

8. Secondary Outcome

Title	Usability Endpoint: Amount of Saliva That Exited the Mouth After Film Placement
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

Outcome Measure Data

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
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
Measure Participants	33	33
Participants with 0 mL saliva exiting the mouth	33 94.3%	31 NaN
Participants with 1 mL saliva exiting the mouth	0 0%	1 NaN
Participants with 2 mL saliva exiting the mouth	0 0%	1 NaN

Adverse Events

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).
Arm/Group Title	Interictal State (Period A)		Ictal/Peri-ictal State (Period B)
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/33 (0%)
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%)		1/33 (3%)
Nervous system disorders
HOSPITALIZATION DUE TO SEIZURE CLUSTER	0/33 (0%)	0	1/33 (3%)	1
Other (Not Including Serious) Adverse Events
	Interictal State (Period A)		Ictal/Peri-ictal State (Period B)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/33 (36.4%)		14/33 (42.4%)
Gastrointestinal disorders
Diarrhoea	0/33 (0%)	0	1/33 (3%)	1
Nervous system disorders
Complex Partial Seizures	9/33 (27.3%)	9	14/33 (42.4%)	14
Headache	0/33 (0%)	0	3/33 (9.1%)	3
Generalized tonic-clonic seizure	1/33 (3%)	6	1/33 (3%)	3
Seizure	1/33 (3%)	2	1/33 (3%)	4
Somnolence	2/33 (6.1%)	3	0/33 (0%)	0
Seizure cluster	0/33 (0%)	0	1/33 (3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Trial results were included as confidential information and required written sponsor approval.