Trial Outcomes & Findings for Safety and Tolerability Study of Diazepam Buccal Film (DBF) in Subjects With Epilepsy (NCT NCT03428360)

NCT ID: NCT03428360

Last Updated: 2021-08-05

Results Overview

A TEAE was defined as any adverse event with onset date on the day of or after administration of study drug including relationship and severity.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 149 participants
• Primary outcome timeframe: Adverse events (AEs) were recorded from Day 1 through the last study contact (Month 7 telephone contact).
• Results posted on: 2021-08-05

Participant Flow

150 subjects with epilepsy passed screening but 1 was never enrolled

149 were enrolled but only 130 received at least 1 dose of study drug and were included in the analyses

Participant milestones

Measure	Safety Set Male or female subjects between the ages of 2 and 65 years who had an established diagnosis of epilepsy exhibited by motor seizures with clear alteration of awareness, and while on a regimen of anti-epileptic medication(s), still experienced bouts of seizures (frequent breakthrough seizures, eg, seizure clusters) and who, in the opinion of the Investigator, could need benzodiazepine intervention for seizure control at least 1 time a month on average. Subjects must have been on at least 1 concomitant anti-epileptic drug at screening. Diazepam Buccal Soluble Film 5, 7.5,10, 12.5,15 or 17.5 mg with individual dose determined according to age and weight category: The subjects administered DBF themselves or with the help of a caregiver, (trained by the study site staff in study drug administration and documentation) in the same setting as they typically used the diazepam rectal gel or other rescue medication, without the presence of study staff.
Overall Study STARTED	130
Overall Study COMPLETED	90
Overall Study NOT COMPLETED	40

Reasons for withdrawal

Measure	Safety Set Male or female subjects between the ages of 2 and 65 years who had an established diagnosis of epilepsy exhibited by motor seizures with clear alteration of awareness, and while on a regimen of anti-epileptic medication(s), still experienced bouts of seizures (frequent breakthrough seizures, eg, seizure clusters) and who, in the opinion of the Investigator, could need benzodiazepine intervention for seizure control at least 1 time a month on average. Subjects must have been on at least 1 concomitant anti-epileptic drug at screening. Diazepam Buccal Soluble Film 5, 7.5,10, 12.5,15 or 17.5 mg with individual dose determined according to age and weight category: The subjects administered DBF themselves or with the help of a caregiver, (trained by the study site staff in study drug administration and documentation) in the same setting as they typically used the diazepam rectal gel or other rescue medication, without the presence of study staff.
Overall Study Informed consent withdrawn	5
Overall Study Withdrawal by Subject	4
Overall Study Lost to Follow-up	5
Overall Study Physician Decision	2
Overall Study Study terminated by sponsor	10
Overall Study Non-compliant with study	1
Overall Study Non-compliant with study drug	3
Overall Study Death	3
Overall Study Adverse Event	1
Overall Study Not on antiepileptic drug	1

Baseline Characteristics

Safety and Tolerability Study of Diazepam Buccal Film (DBF) in Subjects With Epilepsy

Baseline characteristics by cohort

Measure	Safety Analysis Set: Enrolled Subjects With Epilepsy Who Received at Least 1 Dose of Study Drug n=130 Participants Male or female subjects between the ages of 2 and 65 years who had an established diagnosis of epilepsy exhibited by motor seizures with clear alteration of awareness, and while on a regimen of anti-epileptic medication(s), still experienced bouts of seizures (frequent breakthrough seizures, eg, seizure clusters) and who, in the opinion of the Investigator, could need benzodiazepine intervention for seizure control at least 1 time a month on average. Subjects must have been on at least 1 concomitant anti-epileptic drug at screening. Diazepam Buccal Soluble Film 5, 7.5,10, 12.5,15 or 17.5 mg with individual dose determined according to age and weight category: The subjects in this study administered DBF themselves or with the help of a caregiver, (trained by the study site staff in study drug administration and documentation) in the same setting as they typically used the diazepam rectal gel or other rescue medication, without the presence of study staff.
Age, Continuous	25.9 years STANDARD_DEVIATION 13.28 • n=5 Participants
Sex: Female, Male Female	66 Participants n=5 Participants
Sex: Female, Male Male	64 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	29 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	99 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	6 Participants n=5 Participants
Race (NIH/OMB) Black or African American	12 Participants n=5 Participants
Race (NIH/OMB) White	99 Participants n=5 Participants
Race (NIH/OMB) More than one race	8 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Body Mass Index (kg/m^2	24.108 kg/m^2 STANDARD_DEVIATION 6.8148 • n=5 Participants

PRIMARY outcome

Timeframe: Adverse events (AEs) were recorded from Day 1 through the last study contact (Month 7 telephone contact).

Population: Subjects who received at least 1 dose of study drug

A TEAE was defined as any adverse event with onset date on the day of or after administration of study drug including relationship and severity.

Outcome measures

Measure	Safety Analysis Set: Enrolled Subjects With Epilepsy Who Received at Least 1 Dose of Study Drug n=130 Participants Male or female subjects between the ages of 2 and 65 years who had an established diagnosis of epilepsy exhibited by motor seizures with clear alteration of awareness, and while on a regimen of anti-epileptic medication(s), still experienced bouts of seizures (frequent breakthrough seizures, eg, seizure clusters) and who, in the opinion of the Investigator, could need benzodiazepine intervention for seizure control at least 1 time a month on average. Subjects must have been on at least 1 concomitant anti-epileptic drug at screening. Diazepam Buccal Soluble Film 5, 7.5,10, 12.5,15 or 17.5 mg with individual dose determined according to age and weight category: The subjects in this study administered DBF themselves or with the help of a caregiver, (trained by the study site staff in study drug administration and documentation) in the same setting as they typically used the diazepam rectal gel or other rescue medication, without the presence of study staff.
Number of Subjects in the Safety Analysis Set With at Least 1 Treatment-emergent Adverse Event (TEAE) At least 1 TEAE	84 Participants
Number of Subjects in the Safety Analysis Set With at Least 1 Treatment-emergent Adverse Event (TEAE) At least 1 severe TEAE	14 Participants
Number of Subjects in the Safety Analysis Set With at Least 1 Treatment-emergent Adverse Event (TEAE) At least 1 study drug related TEAE	10 Participants
Number of Subjects in the Safety Analysis Set With at Least 1 Treatment-emergent Adverse Event (TEAE) At least 1 severe and related TEAE	1 Participants
Number of Subjects in the Safety Analysis Set With at Least 1 Treatment-emergent Adverse Event (TEAE) At least 1 serious TEAE	18 Participants
Number of Subjects in the Safety Analysis Set With at Least 1 Treatment-emergent Adverse Event (TEAE) At least 1 serious and related TEAE	1 Participants

PRIMARY outcome

Timeframe: AESIs were recorded from Day 1 through the last study contact (Month 7 telephone contact).

Population: Subjects who received at least 1 dose of study drug

A.Oral irritation related AEs including but not limited to: buccal mucosal swelling, mouth ulceration, injuries to oral cavity (such as tongue or mucosal laceration, broken tooth, bleeding), erythema, stomatitis, gingivitis, xerostomia, staining, dysphagia, dysgeusia, burning, stinging, tingling.

B. Abuse related AEs including euphoria, euphoric mood, feeling of relaxation, anger, dissociative effects, hallucinations, psychosis, changes in mood, impaired cognition, attention, psychomotor effects, inappropriate affect, overdose, and misuse.

C. Other: Respiratory disorders, nervous system disorders

Outcome measures

Measure	Safety Analysis Set: Enrolled Subjects With Epilepsy Who Received at Least 1 Dose of Study Drug n=130 Participants Male or female subjects between the ages of 2 and 65 years who had an established diagnosis of epilepsy exhibited by motor seizures with clear alteration of awareness, and while on a regimen of anti-epileptic medication(s), still experienced bouts of seizures (frequent breakthrough seizures, eg, seizure clusters) and who, in the opinion of the Investigator, could need benzodiazepine intervention for seizure control at least 1 time a month on average. Subjects must have been on at least 1 concomitant anti-epileptic drug at screening. Diazepam Buccal Soluble Film 5, 7.5,10, 12.5,15 or 17.5 mg with individual dose determined according to age and weight category: The subjects in this study administered DBF themselves or with the help of a caregiver, (trained by the study site staff in study drug administration and documentation) in the same setting as they typically used the diazepam rectal gel or other rescue medication, without the presence of study staff.
Number of Subjects in Safety Analysis Set With Adverse Events of Special Interest (AESI) Any adverse event of special interest	32 participants
Number of Subjects in Safety Analysis Set With Adverse Events of Special Interest (AESI) Any oral irritation adverse event	3 participants
Number of Subjects in Safety Analysis Set With Adverse Events of Special Interest (AESI) Any oral safety adverse event	8 participants
Number of Subjects in Safety Analysis Set With Adverse Events of Special Interest (AESI) Any potential abuse related adverse event	21 participants
Number of Subjects in Safety Analysis Set With Adverse Events of Special Interest (AESI) Any abuse related adverse event	1 participants
Number of Subjects in Safety Analysis Set With Adverse Events of Special Interest (AESI) Any other adverse event of special interest	8 participants

SECONDARY outcome

Timeframe: Recorded in an electronic diary after each use of study drug, throughout the course of the study; approximately 6 months

Population: Subjects who received at least 1 dose of study drug (Safety Analysis Set)

For each use occasion the following question was asked: Did you have difficulty in opening the outer plastic packaging on this use occasion? Yes

Outcome measures

Measure

Safety Analysis Set: Enrolled Subjects With Epilepsy Who Received at Least 1 Dose of Study Drug n=1348 total number of use occasions Male or female subjects between the ages of 2 and 65 years who had an established diagnosis of epilepsy exhibited by motor seizures with clear alteration of awareness, and while on a regimen of anti-epileptic medication(s), still experienced bouts of seizures (frequent breakthrough seizures, eg, seizure clusters) and who, in the opinion of the Investigator, could need benzodiazepine intervention for seizure control at least 1 time a month on average. Subjects must have been on at least 1 concomitant anti-epileptic drug at screening. Diazepam Buccal Soluble Film 5, 7.5,10, 12.5,15 or 17.5 mg with individual dose determined according to age and weight category: The subjects in this study administered DBF themselves or with the help of a caregiver, (trained by the study site staff in study drug administration and documentation) in the same setting as they typically used the diazepam rectal gel or other rescue medication, without the presence of study staff.

Usability Assessment: Number of Use Occasions Where Difficulty in Opening the Outer Packaging Was Recorded.

211 total number of use occasions

SECONDARY outcome

Timeframe: Recorded in an electronic diary after each use of study drug, throughout the course of the study; approximately 6 months

Population: Number of subjects reporting use occasions

For each use occasion the following question was asked: Did you have difficulty in opening the foil pouch on this use occasion? Yes or No

Outcome measures

Measure	Safety Analysis Set: Enrolled Subjects With Epilepsy Who Received at Least 1 Dose of Study Drug n=1348 total number of use occasions Male or female subjects between the ages of 2 and 65 years who had an established diagnosis of epilepsy exhibited by motor seizures with clear alteration of awareness, and while on a regimen of anti-epileptic medication(s), still experienced bouts of seizures (frequent breakthrough seizures, eg, seizure clusters) and who, in the opinion of the Investigator, could need benzodiazepine intervention for seizure control at least 1 time a month on average. Subjects must have been on at least 1 concomitant anti-epileptic drug at screening. Diazepam Buccal Soluble Film 5, 7.5,10, 12.5,15 or 17.5 mg with individual dose determined according to age and weight category: The subjects in this study administered DBF themselves or with the help of a caregiver, (trained by the study site staff in study drug administration and documentation) in the same setting as they typically used the diazepam rectal gel or other rescue medication, without the presence of study staff.
Usability Assessment: Ability to Open Foil Pouch on Each Use Occasion Yes, I had difficulty opening the foil pouch	391 total number of use occasions
Usability Assessment: Ability to Open Foil Pouch on Each Use Occasion No, I did not have difficulty opening the foil pouch	957 total number of use occasions

SECONDARY outcome

Timeframe: Recorded in an electronic diary after each use of study drug, throughout the course of the study; approximately 6 months

Population: Subjects who received at least 1 dose of study drug (Safety Analysis Set)

For each use occasion the following question was asked: Did you have difficulty in removing study drug from foil pouch on this occasion? Yes or No

Outcome measures

Measure	Safety Analysis Set: Enrolled Subjects With Epilepsy Who Received at Least 1 Dose of Study Drug n=1348 total number of use occasions rpoeted Male or female subjects between the ages of 2 and 65 years who had an established diagnosis of epilepsy exhibited by motor seizures with clear alteration of awareness, and while on a regimen of anti-epileptic medication(s), still experienced bouts of seizures (frequent breakthrough seizures, eg, seizure clusters) and who, in the opinion of the Investigator, could need benzodiazepine intervention for seizure control at least 1 time a month on average. Subjects must have been on at least 1 concomitant anti-epileptic drug at screening. Diazepam Buccal Soluble Film 5, 7.5,10, 12.5,15 or 17.5 mg with individual dose determined according to age and weight category: The subjects in this study administered DBF themselves or with the help of a caregiver, (trained by the study site staff in study drug administration and documentation) in the same setting as they typically used the diazepam rectal gel or other rescue medication, without the presence of study staff.
Usability Assessment: Ability to Remove Study Drug From Foil Pouch on Each Use Occasion Yes, I had difficulty removing study drug from pouch on this occasion	47 total number of use occasions rpoeted
Usability Assessment: Ability to Remove Study Drug From Foil Pouch on Each Use Occasion No, I did not have difficulty removing study drug from the pouch on this occasion	1301 total number of use occasions rpoeted

SECONDARY outcome

Timeframe: Recorded in an electronic diary after each use of study drug, throughout the course of the study; approximately 6 months

Population: Subjects who received at least 1 dose of study drug (Safety Analysis Set)

Of the total number of use occasions over the course of the study, the number of use occasions that were successfully inserted/retained in the cheek

Outcome measures

Measure

Safety Analysis Set: Enrolled Subjects With Epilepsy Who Received at Least 1 Dose of Study Drug n=1348 total number of use occasions Male or female subjects between the ages of 2 and 65 years who had an established diagnosis of epilepsy exhibited by motor seizures with clear alteration of awareness, and while on a regimen of anti-epileptic medication(s), still experienced bouts of seizures (frequent breakthrough seizures, eg, seizure clusters) and who, in the opinion of the Investigator, could need benzodiazepine intervention for seizure control at least 1 time a month on average. Subjects must have been on at least 1 concomitant anti-epileptic drug at screening. Diazepam Buccal Soluble Film 5, 7.5,10, 12.5,15 or 17.5 mg with individual dose determined according to age and weight category: The subjects in this study administered DBF themselves or with the help of a caregiver, (trained by the study site staff in study drug administration and documentation) in the same setting as they typically used the diazepam rectal gel or other rescue medication, without the presence of study staff.

Number of Occasions With Successful Insertion/Retention in Cheek

1330 Number of events

SECONDARY outcome

Timeframe: Recorded in an electronic diary after each use of study drug, throughout the course of the study; approximately 6 months

Population: Subjects who received at least 1 dose of study drug (Safety Analysis Set)

Number of occasions where it took 1 attempt to insert film, Number of occasions where it took 2 attempts to insert film, Number of occasions where it took 3 attempts to insert film, Number of occasions where it took >3 attempts to insert film

Outcome measures

Measure	Safety Analysis Set: Enrolled Subjects With Epilepsy Who Received at Least 1 Dose of Study Drug n=1348 total number of use occasions Male or female subjects between the ages of 2 and 65 years who had an established diagnosis of epilepsy exhibited by motor seizures with clear alteration of awareness, and while on a regimen of anti-epileptic medication(s), still experienced bouts of seizures (frequent breakthrough seizures, eg, seizure clusters) and who, in the opinion of the Investigator, could need benzodiazepine intervention for seizure control at least 1 time a month on average. Subjects must have been on at least 1 concomitant anti-epileptic drug at screening. Diazepam Buccal Soluble Film 5, 7.5,10, 12.5,15 or 17.5 mg with individual dose determined according to age and weight category: The subjects in this study administered DBF themselves or with the help of a caregiver, (trained by the study site staff in study drug administration and documentation) in the same setting as they typically used the diazepam rectal gel or other rescue medication, without the presence of study staff.
Usability Assessment: Difficulty Inserting DBF Against the Buccal Mucosa (Number of Attempts to Insert Film for Each Use Occasion) Number of occasions where it required 1 attempt to insert film	1268 Number of events
Usability Assessment: Difficulty Inserting DBF Against the Buccal Mucosa (Number of Attempts to Insert Film for Each Use Occasion) Number of occasions that required 2 attempts to insert film	38 Number of events
Usability Assessment: Difficulty Inserting DBF Against the Buccal Mucosa (Number of Attempts to Insert Film for Each Use Occasion) Number of occasions that required 3 attempts to insert film	18 Number of events
Usability Assessment: Difficulty Inserting DBF Against the Buccal Mucosa (Number of Attempts to Insert Film for Each Use Occasion) Number of occasions that required >3 attempts to insert film	6 Number of events

SECONDARY outcome

Timeframe: Recorded in an electronic diary after each use of study drug, throughout the course of the study; approximately 6 months

Population: Subjects who received at least 1 dose of study drug (Safety Analysis Set)

Number of occasions where the study drug was not successfully placed and or retained in cheek until the film fully dissolved.

Outcome measures

Measure

Safety Analysis Set: Enrolled Subjects With Epilepsy Who Received at Least 1 Dose of Study Drug n=1348 total number of use occasions Male or female subjects between the ages of 2 and 65 years who had an established diagnosis of epilepsy exhibited by motor seizures with clear alteration of awareness, and while on a regimen of anti-epileptic medication(s), still experienced bouts of seizures (frequent breakthrough seizures, eg, seizure clusters) and who, in the opinion of the Investigator, could need benzodiazepine intervention for seizure control at least 1 time a month on average. Subjects must have been on at least 1 concomitant anti-epileptic drug at screening. Diazepam Buccal Soluble Film 5, 7.5,10, 12.5,15 or 17.5 mg with individual dose determined according to age and weight category: The subjects in this study administered DBF themselves or with the help of a caregiver, (trained by the study site staff in study drug administration and documentation) in the same setting as they typically used the diazepam rectal gel or other rescue medication, without the presence of study staff.

Usability Assessment: Number of Occasions Where DBF Was Not Placed or Retained on the Inner Cheek Until Dissolution

16 total number of use occasions

SECONDARY outcome

Timeframe: Recorded in an electronic diary after each use of study drug, throughout the course of the study; approximately 6 months

Population: Subjects who received at least 1 dose of study drug (Safety Analysis Set)

Reasons for multiple attempts at insertion Multiple choice answer was: Excessive drooling, Clenching jaw / Won't open mouth, Spit out before sticking, Other/None of the above

Outcome measures

Measure	Safety Analysis Set: Enrolled Subjects With Epilepsy Who Received at Least 1 Dose of Study Drug n=1348 total number of use occasions Male or female subjects between the ages of 2 and 65 years who had an established diagnosis of epilepsy exhibited by motor seizures with clear alteration of awareness, and while on a regimen of anti-epileptic medication(s), still experienced bouts of seizures (frequent breakthrough seizures, eg, seizure clusters) and who, in the opinion of the Investigator, could need benzodiazepine intervention for seizure control at least 1 time a month on average. Subjects must have been on at least 1 concomitant anti-epileptic drug at screening. Diazepam Buccal Soluble Film 5, 7.5,10, 12.5,15 or 17.5 mg with individual dose determined according to age and weight category: The subjects in this study administered DBF themselves or with the help of a caregiver, (trained by the study site staff in study drug administration and documentation) in the same setting as they typically used the diazepam rectal gel or other rescue medication, without the presence of study staff.
Usability Assessment: Reasons for Multiple Placement/Insertion Attempts During a Use Occasion Clenching jaw / won't open mouth	21 total number of use occasions
Usability Assessment: Reasons for Multiple Placement/Insertion Attempts During a Use Occasion Excessive drooling	24 total number of use occasions
Usability Assessment: Reasons for Multiple Placement/Insertion Attempts During a Use Occasion Spit out before sticking	17 total number of use occasions
Usability Assessment: Reasons for Multiple Placement/Insertion Attempts During a Use Occasion Other (none of the above)	33 total number of use occasions

Adverse Events

Safety Analysis Set

Serious events: 17 serious events

Other events: 84 other events

Deaths: 3 deaths

Serious adverse events

Measure	Safety Analysis Set n=130 participants at risk Male or female subjects between the ages of 2 and 65 years who had an established diagnosis of epilepsy exhibited by motor seizures with clear alteration of awareness, and while on a regimen of anti-epileptic medication(s), still experienced bouts of seizures (frequent breakthrough seizures, eg, seizure clusters) and who, in the opinion of the Investigator, could need benzodiazepine intervention for seizure control at least 1 time a month on average. Subjects must have been on at least 1 concomitant anti-epileptic drug at screening. Diazepam Buccal Soluble Film 5, 7.5,10, 12.5,15 or 17.5 mg with individual dose determined according to age and weight category: The subjects in this study administered DBF themselves or with the help of a caregiver, (trained by the study site staff in study drug administration and documentation) in the same setting as they typically used the diazepam rectal gel or other rescue medication, without the presence of study staff.
Nervous system disorders Seizure	0.77% 1/130 • Number of events 1 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
Nervous system disorders Epilepsy	0.77% 1/130 • Number of events 1 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
Nervous system disorders Partial seizure	0.77% 1/130 • Number of events 1 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
Respiratory, thoracic and mediastinal disorders Aspiration	0.77% 1/130 • Number of events 3 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.77% 1/130 • Number of events 1 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.77% 1/130 • Number of events 1 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.77% 1/130 • Number of events 1 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
Gastrointestinal disorders Enterocolitis	0.77% 1/130 • Number of events 1 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
Gastrointestinal disorders Nausea	0.77% 1/130 • Number of events 1 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
Gastrointestinal disorders Small bowel obstruction	0.77% 1/130 • Number of events 1 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
Gastrointestinal disorders Vomiting	0.77% 1/130 • Number of events 1 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
Injury, poisoning and procedural complications Joint dislocation	0.77% 1/130 • Number of events 1 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
Injury, poisoning and procedural complications Toxicity to various agents	0.77% 1/130 • Number of events 1 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
Infections and infestations Pneumonia	0.77% 1/130 • Number of events 1 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
Metabolism and nutrition disorders Hypokalaemia	0.77% 1/130 • Number of events 1 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain neoplasm malignant	0.77% 1/130 • Number of events 1 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
General disorders Death	0.77% 1/130 • Number of events 1 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).

Other adverse events

Measure	Safety Analysis Set n=130 participants at risk Male or female subjects between the ages of 2 and 65 years who had an established diagnosis of epilepsy exhibited by motor seizures with clear alteration of awareness, and while on a regimen of anti-epileptic medication(s), still experienced bouts of seizures (frequent breakthrough seizures, eg, seizure clusters) and who, in the opinion of the Investigator, could need benzodiazepine intervention for seizure control at least 1 time a month on average. Subjects must have been on at least 1 concomitant anti-epileptic drug at screening. Diazepam Buccal Soluble Film 5, 7.5,10, 12.5,15 or 17.5 mg with individual dose determined according to age and weight category: The subjects in this study administered DBF themselves or with the help of a caregiver, (trained by the study site staff in study drug administration and documentation) in the same setting as they typically used the diazepam rectal gel or other rescue medication, without the presence of study staff.
Nervous system disorders Seizure	20.0% 26/130 • Number of events 98 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
Nervous system disorders Somnolence	4.6% 6/130 • Number of events 6 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
Nervous system disorders Lethargy	3.1% 4/130 • Number of events 5 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
Nervous system disorders Dizziness	3.1% 4/130 • Number of events 4 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
Nervous system disorders Headache	3.1% 4/130 • Number of events 4 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
Infections and infestations Upper respiratory tract infection	6.2% 8/130 • Number of events 8 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
Infections and infestations Sinusitis	4.6% 6/130 • Number of events 6 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
Infections and infestations Ear infection	3.1% 4/130 • Number of events 4 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
Gastrointestinal disorders Vomiting	5.4% 7/130 • Number of events 8 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
Gastrointestinal disorders Nausea	3.8% 5/130 • Number of events 5 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
Gastrointestinal disorders Diarrhoea	3.1% 4/130 • Number of events 6 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
Injury, poisoning and procedural complications Fall	3.8% 5/130 • Number of events 7 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
Injury, poisoning and procedural complications Skin abrasion	3.1% 4/130 • Number of events 5 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
Respiratory, thoracic and mediastinal disorders Cough	3.8% 5/130 • Number of events 6 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	3.1% 4/130 • Number of events 4 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
General disorders Pyrexia	5.4% 7/130 • Number of events 12 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
Investigations Weight decreased	3.1% 4/130 • Number of events 6 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).
Investigations Weight increased	3.1% 4/130 • Number of events 6 • Adverse events that started after the first intake of DBF through the Final Visit were considered treatment-emergent adverse events (TEAEs).

Additional Information

Clinical Project Manager

Aquestive Therapeutics

Phone: 9089411896

Email: cbuan@aquestive.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60