Trial Outcomes & Findings for Diazepam Buccal Film (DBF) - Diastat Rectal Gel (DRG) Crossover Study (NCT NCT03953820)
NCT ID: NCT03953820
Last Updated: 2020-08-18
Results Overview
Area Under Plasma Concentration-Time Curve From Time Zero to the last non-zero concentration
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
31 participants
Primary outcome timeframe
0.5, 0.75, 1, 105, 2, 3, 4, 6, 9, 12, 24, 48, 72, 96, 120, 144, 192, and 240 hours post-dose
Results posted on
2020-08-18
Participant Flow
A total of 43 healthy (except for seizure disorder) volunteers were screened for eligibility in this study.
31 of the 43 screening participants were enrolled and randomized at 5 study sites in the United States. Of those not randomized, 7 did not meet protocol eligibility criteria and 5 were judged eligible but decided not to participate or were not selected to participate in the study since there was already a sufficient number of subjects.
Participant milestones
| Measure |
Diazepam Buccal Film, Then Diastat Rectal Gel
Subjects received a single dose of Diazepam Buccal Film and Diastat Rectal Gel following a moderate-fat meal in a randomized sequence with a 28-day washout period between doses.
Diazepam Buccal Film was administered on the inner aspect of the cheek according to the recommended dose regimen (10 mg to 17.5 mg according to body weight) allowing transbuccal absorption of diazepam.
|
Diastat Rectal Gel, Then Diazepam Buccal Film
Subjects received a single dose of Diastat Rectal Gel and Diazepam Buccal Film following a moderate-fat meal in a randomized sequence with a 28-day washout period between doses.
Diastat Rectal Gel was administered rectally according to package insert dosing instructions (10 mg to 20 mg according to body weight) allowing rectal absorption of diazepam.
|
Diazepam Buccal Film Following a High-Fat Meal
Subjects who completed Periods 1 and 2 were asked to participate in Period 3 on a voluntary basis.
Subjects who volunteered to participate in Period 3 received a second dose of DBF at the same dose and in the same manner as the earlier dose of DBF with the exception was administered following a high-fat meal.
|
|---|---|---|---|
|
Two-Sequence, Two-Way Crossover
STARTED
|
15
|
16
|
0
|
|
Two-Sequence, Two-Way Crossover
COMPLETED
|
13
|
16
|
0
|
|
Two-Sequence, Two-Way Crossover
NOT COMPLETED
|
2
|
0
|
0
|
|
DBF Following High-Fat Meal
STARTED
|
0
|
0
|
10
|
|
DBF Following High-Fat Meal
COMPLETED
|
0
|
0
|
10
|
|
DBF Following High-Fat Meal
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Diazepam Buccal Film, Then Diastat Rectal Gel
Subjects received a single dose of Diazepam Buccal Film and Diastat Rectal Gel following a moderate-fat meal in a randomized sequence with a 28-day washout period between doses.
Diazepam Buccal Film was administered on the inner aspect of the cheek according to the recommended dose regimen (10 mg to 17.5 mg according to body weight) allowing transbuccal absorption of diazepam.
|
Diastat Rectal Gel, Then Diazepam Buccal Film
Subjects received a single dose of Diastat Rectal Gel and Diazepam Buccal Film following a moderate-fat meal in a randomized sequence with a 28-day washout period between doses.
Diastat Rectal Gel was administered rectally according to package insert dosing instructions (10 mg to 20 mg according to body weight) allowing rectal absorption of diazepam.
|
Diazepam Buccal Film Following a High-Fat Meal
Subjects who completed Periods 1 and 2 were asked to participate in Period 3 on a voluntary basis.
Subjects who volunteered to participate in Period 3 received a second dose of DBF at the same dose and in the same manner as the earlier dose of DBF with the exception was administered following a high-fat meal.
|
|---|---|---|---|
|
Two-Sequence, Two-Way Crossover
Adverse Event
|
1
|
0
|
0
|
|
Two-Sequence, Two-Way Crossover
Physician Decision
|
1
|
0
|
0
|
Baseline Characteristics
Diazepam Buccal Film (DBF) - Diastat Rectal Gel (DRG) Crossover Study
Baseline characteristics by cohort
| Measure |
Overall Population
n=31 Participants
31 participants were enrolled and randomized to one of two treatment sequences with a 28-day washout period between doses:
Treatment A was a single dose Diazepam Buccal Film administered on the inner aspect of the cheek according to the recommended dose regimen (10 mg to 17.5 mg according to body weight) following a moderate-fat meal.
Treatment B was Diastat Rectal Gel administered rectally according to the package insert dosing instructions (10 mg to 20 mg according to body weight) following a moderate-fat meal.
Treatment C was a voluntary second dose of Diazepam Buccal Film administered at the same dose and in the same manner as the earlier dose of Diazepam Buccal Film with the exception of administration following a high-fat meal.
|
|---|---|
|
Age, Continuous
|
40.4 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
23 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
23 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 0.5, 0.75, 1, 105, 2, 3, 4, 6, 9, 12, 24, 48, 72, 96, 120, 144, 192, and 240 hours post-dosePopulation: Subjects who received both DBF and DRF administered following moderate fat meal with no significant violation of study restrictions, and for whom pharmacokinetic profile could be adequately characterized.
Area Under Plasma Concentration-Time Curve From Time Zero to the last non-zero concentration
Outcome measures
| Measure |
DBF Following Moderate-Fat Meal
n=29 Participants
Subjects received Diazepam Buccal Film administered on the inner aspect of the cheek following ingestion of a moderate-fat meal, allowing for transbuccal absorption of diazepam.
|
DRG Following a Moderate Fat Meal
n=28 Participants
Subjects received Diastat AcuDial Rectal Gel administered rectally following ingestion of a moderate-fat meal, allowing for rectal absorption of diazepam.
|
DBF Following a High Fat Meal
n=10 Participants
Subjects received Diazepam Buccal Film administered on the inner aspect of the cheek following ingestion of a high-fat meal, allowing for transbuccal absorption of diazepam.
|
|---|---|---|---|
|
AUC 0-t
|
7290.40 hr*ng/mL
Interval 5935.35 to 8954.81
|
5682.09 hr*ng/mL
Interval 4625.97 to 6979.31
|
8288.63 hr*ng/mL
Interval 6801.31 to 10100.0
|
PRIMARY outcome
Timeframe: 0.5, 0.75, 1, 105, 2, 3, 4, 6, 9, 12, 24, 48, 72, 96, 120, 144, 192, and 240 hours post-dosePopulation: Subjects who received both DBF and DRF administered following moderate fat meal with no significant violation of study restrictions, and for whom pharmacokinetic profile could be adequately characterized.
Area under concentration time curve, from time 0 extrapolated to infinity
Outcome measures
| Measure |
DBF Following Moderate-Fat Meal
n=29 Participants
Subjects received Diazepam Buccal Film administered on the inner aspect of the cheek following ingestion of a moderate-fat meal, allowing for transbuccal absorption of diazepam.
|
DRG Following a Moderate Fat Meal
n=27 Participants
Subjects received Diastat AcuDial Rectal Gel administered rectally following ingestion of a moderate-fat meal, allowing for rectal absorption of diazepam.
|
DBF Following a High Fat Meal
n=10 Participants
Subjects received Diazepam Buccal Film administered on the inner aspect of the cheek following ingestion of a high-fat meal, allowing for transbuccal absorption of diazepam.
|
|---|---|---|---|
|
AUC 0-inf
|
8672.09 hr*ng/mL
Interval 7553.47 to 9956.32
|
6880.96 hr*ng/mL
Interval 5993.38 to 7899.98
|
8903.79 hr*ng/mL
Interval 7500.99 to 10568.93
|
PRIMARY outcome
Timeframe: 0.5, 0.75, 1, 105, 2, 3, 4, 6, 9, 12, 24, 48, 72, 96, 120, 144, 192, and 240 hours post-dosePopulation: Subjects who received both DBF and DRF administered following moderate fat meal with no significant violation of study restrictions, and for whom pharmacokinetic profile could be adequately characterized.
Maximum observed plasma concentration
Outcome measures
| Measure |
DBF Following Moderate-Fat Meal
n=29 Participants
Subjects received Diazepam Buccal Film administered on the inner aspect of the cheek following ingestion of a moderate-fat meal, allowing for transbuccal absorption of diazepam.
|
DRG Following a Moderate Fat Meal
n=27 Participants
Subjects received Diastat AcuDial Rectal Gel administered rectally following ingestion of a moderate-fat meal, allowing for rectal absorption of diazepam.
|
DBF Following a High Fat Meal
n=10 Participants
Subjects received Diazepam Buccal Film administered on the inner aspect of the cheek following ingestion of a high-fat meal, allowing for transbuccal absorption of diazepam.
|
|---|---|---|---|
|
Cmax
|
204.25 ng/mL
Interval 163.41 to 255.32
|
211.22 ng/mL
Interval 168.98 to 264.02
|
181.61 ng/mL
Interval 138.08 to 240.6
|
Adverse Events
Diazepam Buccal Film Following a Moderate-Fat Meal
Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths
Diastat Rectal Gel Following a Moderate-Fat Meal
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Diazepam Buccal Film Following a High-Fat Meal
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Diazepam Buccal Film Following a Moderate-Fat Meal
n=31 participants at risk
Participants received a single dose of Diazepam Buccal Film and Diastat Rectal Gel following a moderate-fat meal in a randomized sequence with a 28-day washout period between doses.
Diazepam Buccal Film was administered on the inner aspect of the cheek according to the recommended dose regimen (10 mg to 17.5 mg according to body weight) allowing transbuccal absorption of diazepam.
|
Diastat Rectal Gel Following a Moderate-Fat Meal
n=29 participants at risk
Participants received a single dose of Diazepam Buccal Film and Diastat Rectal Gel following a moderate-fat meal in a randomized sequence with a 28-day washout period between doses.
Diastat Rectal Gel was administered rectally according to package insert dosing instructions (10 mg to 20 mg according to body weight) allowing rectal absorption of diazepam.
|
Diazepam Buccal Film Following a High-Fat Meal
n=10 participants at risk
Participants who volunteered to participate in the third period received a second dose of Diazepam Buccal Film in exactly the same manner as the earlier dose with the exception that the dose was administered following ingestion of a high-fat meal.
|
|---|---|---|---|
|
Nervous system disorders
Somnolence
|
22.6%
7/31 • Number of events 14 • Adverse event data were collected from the time of signing the Informed Consent until at least 2 weeks following the last study drug administration (50 days overall).
|
20.7%
6/29 • Number of events 14 • Adverse event data were collected from the time of signing the Informed Consent until at least 2 weeks following the last study drug administration (50 days overall).
|
0.00%
0/10 • Adverse event data were collected from the time of signing the Informed Consent until at least 2 weeks following the last study drug administration (50 days overall).
|
|
Nervous system disorders
Headache
|
6.5%
2/31 • Number of events 3 • Adverse event data were collected from the time of signing the Informed Consent until at least 2 weeks following the last study drug administration (50 days overall).
|
6.9%
2/29 • Number of events 2 • Adverse event data were collected from the time of signing the Informed Consent until at least 2 weeks following the last study drug administration (50 days overall).
|
0.00%
0/10 • Adverse event data were collected from the time of signing the Informed Consent until at least 2 weeks following the last study drug administration (50 days overall).
|
|
Nervous system disorders
Dizziness
|
3.2%
1/31 • Number of events 2 • Adverse event data were collected from the time of signing the Informed Consent until at least 2 weeks following the last study drug administration (50 days overall).
|
6.9%
2/29 • Number of events 3 • Adverse event data were collected from the time of signing the Informed Consent until at least 2 weeks following the last study drug administration (50 days overall).
|
0.00%
0/10 • Adverse event data were collected from the time of signing the Informed Consent until at least 2 weeks following the last study drug administration (50 days overall).
|
|
Nervous system disorders
Sedation
|
3.2%
1/31 • Number of events 1 • Adverse event data were collected from the time of signing the Informed Consent until at least 2 weeks following the last study drug administration (50 days overall).
|
6.9%
2/29 • Number of events 2 • Adverse event data were collected from the time of signing the Informed Consent until at least 2 weeks following the last study drug administration (50 days overall).
|
10.0%
1/10 • Number of events 1 • Adverse event data were collected from the time of signing the Informed Consent until at least 2 weeks following the last study drug administration (50 days overall).
|
|
Nervous system disorders
Dysgeusia
|
6.5%
2/31 • Number of events 2 • Adverse event data were collected from the time of signing the Informed Consent until at least 2 weeks following the last study drug administration (50 days overall).
|
0.00%
0/29 • Adverse event data were collected from the time of signing the Informed Consent until at least 2 weeks following the last study drug administration (50 days overall).
|
0.00%
0/10 • Adverse event data were collected from the time of signing the Informed Consent until at least 2 weeks following the last study drug administration (50 days overall).
|
|
General disorders
Fatigue
|
6.5%
2/31 • Number of events 2 • Adverse event data were collected from the time of signing the Informed Consent until at least 2 weeks following the last study drug administration (50 days overall).
|
0.00%
0/29 • Adverse event data were collected from the time of signing the Informed Consent until at least 2 weeks following the last study drug administration (50 days overall).
|
0.00%
0/10 • Adverse event data were collected from the time of signing the Informed Consent until at least 2 weeks following the last study drug administration (50 days overall).
|
Additional Information
Denis Scheper, Director of Portfolio Management and Clinical Operations
Aquestive Therapeutics
Phone: (908)941-1887
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place