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Trial record 4 of 7 for:    aquestive

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

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ClinicalTrials.gov Identifier: NCT03222349
Recruitment Status : Completed
First Posted : July 19, 2017
Results First Posted : May 26, 2021
Last Update Posted : May 26, 2021
Sponsor:
Collaborators:
Syneos Health
Covance
Information provided by (Responsible Party):
Aquestive Therapeutics

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Epilepsy
Intervention Drug: Diazepam Buccal Film
Enrollment 24
Recruitment Details Planned enrollment was 24 male and female subjects with 8 subjects in each of 3 age ranges (2 to 5 years, 6 to 11 years, and 12 to 16 years) with a clinical diagnosis of epilepsy (generalized tonic clonic seizures or focal seizures with impaired awareness) currently receiving at least one epileptic medication who were scheduled for admission to an Epilepsy Monitoring Unit (EMU), General Clinical Research Center (GCRC), or similar facility for evaluation.
Pre-assignment Details A total of 24 subjects were enrolled and received at least 1 dose of study drug based on age and weight during the interictal and the ictal/peri-ictal period in either order as determined by seizure occurrence.
Arm/Group Title Interictal State, Then Ictal/Peri-ictal State Ictal/Peri-ictal State, Then Interictal State
Hide Arm/Group Description The interictal state was defined as a period of time during which 3 hours had elapsed since any clinical postictal signs or symptoms (from the last observed seizure). If clinical and/or electroencephalogram monitoring showed no seizure activity, the subject received DBF single dose determined by age and body weight. The ictal/peri-ictal state was defined as an ongoing clinically observable seizure or seizure activity as verified via EEG. The peri-ictal state was defined as the subject's immediate postictal state following a generalized tonic-clonic (GTC) seizure or focal seizure with impaired awareness, and within 5 minutes after the last clonic jerk. For subjects on EEG monitoring, the peri-ictal state could be defined as less than 5 minutes after cessation of seizure activity (GTC or focal seizure with impaired awareness) as verified via EEG.
Period Title: Overall Study
Started 11 13
Completed 3 6
Not Completed 8 7
Reason Not Completed
Treatment B not done             5             0
Lost to Follow-up             1             2
Withdrawal by Subject             1             0
Treatment A not done             0             5
Study terminated by sponsor             1             0
Arm/Group Title Safety Analysis Set
Hide Arm/Group Description A total of 24 subjects were enrolled and received at least 1 dose of DBF determined based on age and weight (6 in the 2-5 years age group, 9 in the 6-11 years age group, and 9 in the 12-16 years age group).
Overall Number of Baseline Participants 24
Hide Baseline Analysis Population Description
Safety Analysis Set: The safety analysis set comprised all subjects who received at least 1 dose of DBF determined according to the weight and age of the subject.
Age, Categorical   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
<=18 years
24
 100.0%
Between 18 and 65 years
0
   0.0%
>=65 years
0
   0.0%
[1]
Measure Analysis Population Description: Pediatric patients with epilepsy in three age ranges (2-5 years, 6-11 years, 12-16 years) who received at least 1 dose of DBF determined by age and weight
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 24 participants
14.0  (1.58)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
Female
14
  58.3%
Male
10
  41.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
American Indian or Alaska Native
0
   0.0%
Asian
1
   4.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
5
  20.8%
White
14
  58.3%
More than one race
0
   0.0%
Unknown or Not Reported
4
  16.7%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 24 participants
24
 100.0%
Body Mass Index (kg/m^2)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 24 participants
22.166  (10.1980)
1.Primary Outcome
Title Area Under the Concentration Time Curve (AUC) 0 to 4 Hours Post-dose
Hide Description AUC calculated from time 0 (dosing) to 4 hours post-dose in both Period A (interictal administration) and Period B (ictal/peri-ictal administration)
Time Frame Time 0 (dosing), 0.25, 0.5, 1, 1.5, 2, 4 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects in the Pharmacokinetics Population who had data following dosing in both the Interictal State and the Ictal/Peri-ictal State
Arm/Group Title Interictal State Ictal/Peri-ictal State
Hide Arm/Group Description:

Diazepam Buccal Film administered to epileptic patients during interictal state (Period A).

Subjects received a single dose of DBF (range 5 to 17.5 mg) determined on the basis of the subject's age and weight using an interactive web response system during check-in for the subject's first treatment period.

Diazepam Buccal Film administered to epileptic patients during ictal/peri-ictal state (Period B) Subjects received a single dose of DBF (range 5 to 17.5 mg) determined on the basis of the subject's age and weight using an interactive web response system during check-in for the subject's first treatment period.
Overall Number of Participants Analyzed 8 8
Mean (Standard Deviation)
Unit of Measure: hr*ng/mL
739.33  (312.06) 585  (377.11)
2.Primary Outcome
Title Area Under the Concentration Time Curve (AUC) From 0 to 2 Hours Post-dose
Hide Description AUC calculated from time 0 (dosing) to 2 hours post-dose in both Period A (interictal administration) and Period B (ictal/peri-ictal administration)Period A (interictal administration) and Period B (ictal/peri-ictal administration)
Time Frame Time 0 (dosing), 0.25, 0.5, 1, 1.5, 2 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects in the Pharmacokinetics Population who had data following dosing in both the Interictal State and the Ictal/Peri-ictal State
Arm/Group Title Interictal State (Period A) Ictal/Peri-ictal State (Period B)
Hide Arm/Group Description:
Diazepam Buccal Film administered to epileptic patients during interictal state (Period A) Subjects received a single dose of DBF (range 5 to 17.5 mg) determined on the basis of the subject's age and weight using an interactive web response system during check-in for the subject's first treatment period.
Diazepam Buccal Film administered to epileptic patients during ictal/peri-ictal state (Period B) Subjects received a single dose of DBF (range 5 to 17.5 mg) determined on the basis of the subject's age and weight using an interactive web response system during check-in for the subject's first treatment period.
Overall Number of Participants Analyzed 8 8
Mean (Standard Deviation)
Unit of Measure: hr*ng/mL
394.63  (192.47) 309.34  (210.39)
3.Primary Outcome
Title Time When Maximum Plasma Concentration Was Observed (Tmax) 0 to 2 Hours Post-dose
Hide Description Tmax calculated from time 0 (dosing) to 2 hours post-dose in both Period A (interictal administration) and Period B (ictal/peri-ictal administration)
Time Frame Time 0 (dosing), 0.25, 0.5, 1, 1.5, 2 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects in the Pharmacokinetics Population who had data following dosing in both the Interictal State and the Ictal/Peri-ictal State
Arm/Group Title Interictal State (Period A) Ictal/Peri-ictal State (Period B)
Hide Arm/Group Description:
Diazepam Buccal Film administered to epileptic patients during Interictal state (Period A) Subjects received a single dose of DBF (range 5 to 17.5 mg) determined on the basis of the subject's age and weight using an interactive web response system during check-in for the subject's first treatment period.
Diazepam Buccal Film administered to epileptic patients during ictal/peri-ictal state (Period B) Subjects received a single dose of DBF (range 5 to 17.5 mg) determined on the basis of the subject's age and weight using an interactive web response system during check-in for the subject's first treatment period.
Overall Number of Participants Analyzed 8 8
Mean (Standard Deviation)
Unit of Measure: hours
1.196  (0.754) 0.861  (0.574)
4.Primary Outcome
Title Time When Maximum Plasma Concentration Was Observed (Tmax) 0-4 Hours Post-Dose
Hide Description Tmax calculated from dosing (Time 0) to 4 hours post-dose in both Period A (interictal administration) and Period B (ictal/peri-ictal administration)
Time Frame Time 0 (dosing), 0.25, 0.5, 1, 1.5, 2, 4 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects in the Pharmacokinetics Population who had data following dosing in both the Interictal State and the Ictal/Peri-ictal State
Arm/Group Title Interictal Period (Period A) Ictal/Peri-Ictal Period (Period B)
Hide Arm/Group Description:

Each subject received a single dose of DBF based on the subject's age and weight.

Diazepam Buccal Film: Subjects received a single DBF dose determined by age and body weight during the interictal state and during the ictal/peri-ictal period with at least 14 days washout between doses.

Each subject received a single dose of DBF based on the subject's age and weight.

Diazepam Buccal Film: Subjects received a single DBF dose determined by age and body weight during the interictal state and during the ictal/peri-ictal period with at least 14 days washout between doses.

Overall Number of Participants Analyzed 8 8
Mean (Standard Deviation)
Unit of Measure: hours
1.196  (0.754) 0.861  (0.574)
5.Primary Outcome
Title Observed Maximum Plasma Concentration (Cmax) 0-2 Hours
Hide Description Maximum observed plasma concentration measured from Time 0 to 2 hours post-dose in Period A (interictal administration) and Period B (ictal/peri-ictal administration)
Time Frame Time 0 (dosing), 0.25, 0.5, 1, 1.5, 2 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects in the Pharmacokinetics Population who had data following dosing in both the Interictal State and the Ictal/Peri-ictal State
Arm/Group Title Interictal Period (Period A) Ictal/Peri-ictal Period (Period B)
Hide Arm/Group Description:

Each subject received a single dose of DBF based on the subject's age and weight.

Diazepam Buccal Film: Subjects received a single DBF dose determined by age and body weight during the interictal state and during the ictal/peri-ictal period with at least 14 days washout between doses.

Each subject received a single dose of DBF based on the subject's age and weight.

Diazepam Buccal Film: Subjects received a single DBF dose determined by age and body weight during the interictal state and during the ictal/peri-ictal period with at least 14 days washout between doses.

Overall Number of Participants Analyzed 8 8
Mean (Standard Deviation)
Unit of Measure: ng/mL
296.64  (152.82) 233.50  (141.92)
6.Primary Outcome
Title Observed Maximum Plasma Concentration (Cmax) From Time 0 (Dosing) to 4 Hours Post-dose
Hide Description Maximum observed plasma concentration from Time 0 to 4 hours post-dose in Period A (interictal administration) and Period B (ictal/peri-ictal administration)
Time Frame Time 0 (dosing), 0.25, 0.5, 1, 1.5, 2, 4 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects in the Pharmacokinetics Population who had data following dosing in both the Interictal State and the Ictal/Peri-ictal State
Arm/Group Title Interictal State Ictal/Peri-ictal State
Hide Arm/Group Description:

Diazepam Buccal Film administered to epileptic patients during interictal state (Period A).

Subjects received a single dose of DBF (range 5 to 17.5 mg) determined on the basis of the subject's age and weight using an interactive web response system during check-in for the subject's first treatment period.

Diazepam Buccal Film administered to epileptic patients during ictal-peri-ictal state (Period B) Subjects received a single dose of DBF (range 5 to 17.5 mg) determined on the basis of the subject's age and weight using an interactive web response system during check-in for the subject's first treatment period.
Overall Number of Participants Analyzed 8 8
Mean (Standard Deviation)
Unit of Measure: ng/mL
296.64  (152.82) 233.50  (141.92)
7.Secondary Outcome
Title Usability of Diazepam Buccal Film: Number of Subjects Who Spit Out/Moved/Chewed the Film After it Adhered (Stuck) to Buccal Mucosa During Period A and Period B.
Hide Description Was DBF spit out or blown out by the subject after adherence to the buccal mucosa or did the subject chew, talk or move the DBF prior to complete disintegration/dissolution?
Time Frame Period A and Period B from the time of first attempt at DBF insertion to 15 minutes after insertion.
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population comprising all subjects who received at least 1 dose of the study drug in the given study period.
Arm/Group Title Interictal Period (Period A) Ictal/Peri-ictal Period (Period B)
Hide Arm/Group Description:

Each subject received a single dose of DBF based on the subject's age and weight.

Diazepam Buccal Film: Subjects received a single DBF dose determined by age and body weight during the interictal state and during the ictal/peri-ictal period with at least 14 days washout between doses.

Each subject received a single dose of DBF based on the subject's age and weight.

Diazepam Buccal Film: Subjects received a single DBF dose determined by age and body weight during the interictal state and during the ictal/peri-ictal period with at least 14 days washout between doses.

Overall Number of Participants Analyzed 17 16
Measure Type: Count of Participants
Unit of Measure: Participants
3
  17.6%
1
   6.3%
8.Secondary Outcome
Title Usability of Diazepam Buccal Film: Unsuccessful Attempts
Hide Description Number of subjects with any unsuccessful DBF insertion attempts (All analyzed subjects with an unsuccessful attempt ultimately had a successful attempt at dosing)
Time Frame Period A and Period B from the time of first attempt at DBF insertion to 15 minutes after insertion.
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population comprising all subjects who received at least 1 dose of the study drug in the given study period.
Arm/Group Title Interictal Period (Period A) Ictal/Peri-ictal Period (Period B)
Hide Arm/Group Description:

Each subject received a single dose of DBF based on the subject's age and weight.

Diazepam Buccal Film: Subjects received a single DBF dose determined by age and body weight during the interictal state and during the ictal/peri-ictal period with at least 14 days washout between doses.

Each subject received a single dose of DBF based on the subject's age and weight.

Diazepam Buccal Film: Subjects received a single DBF dose determined by age and body weight during the interictal state and during the ictal/peri-ictal period with at least 14 days washout between doses.

Overall Number of Participants Analyzed 17 16
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
4
  25.0%
9.Secondary Outcome
Title Usability Endpoint : Amount of Saliva That Exited the Mouth After DBF Dosing
Hide Description Estimation of the amount of saliva exiting the mouth in mL after DBF dosing in Period A and Period B
Time Frame Period A and Period B from the time of first attempt at DBF insertion to 15 minutes after insertion.
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population comprising all subjects who received at least 1 dose of the study drug in the given study period.
Arm/Group Title Interictal Period (Period A) Ictal/Peri-Ictal Period (Period B)
Hide Arm/Group Description:

Each subject received a single dose of DBF based on the subject's age and weight.

Diazepam Buccal Film: Subjects received a single DBF dose determined by age and body weight during the interictal state and during the ictal/peri-ictal period with at least 14 days washout between doses.

Each subject received a single dose of DBF based on the subject's age and weight.

Diazepam Buccal Film: Subjects received a single DBF dose determined by age and body weight during the interictal state and during the ictal/peri-ictal period with at least 14 days washout between doses.

Overall Number of Participants Analyzed 17 16
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with 0 mL saliva exiting the mouth
13
  76.5%
15
  93.8%
Participants with > 0 mL to ≤ 1 mL saliva exiting the mouth
0
   0.0%
1
   6.3%
Participants with > 1 mL to ≤ 2 mL saliva exiting the mouth
2
  11.8%
0
   0.0%
Participants with > 2 mL to ≤ 3 mL saliva exiting the mouth
1
   5.9%
0
   0.0%
Participants with no data reported or unknown
1
   5.9%
0
   0.0%
10.Secondary Outcome
Title Number of Subjects Who Swallowed DBF After Initial Insertion
Hide Description Number of subjects who swallowed DBF during Period A and/or Period B
Time Frame Period A and Period B from the time of first attempt at DBF insertion to 15 minutes after insertion.
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population comprising all subjects who received at least 1 dose of the study drug.
Arm/Group Title Interictal Period (Period A) Ictal/Peri-ictal Period (Period B)
Hide Arm/Group Description:

Each subject received a single dose of DBF based on the subject's age and weight.

Diazepam Buccal Film: Subjects received a single DBF dose determined by age and body weight during the interictal state and during the ictal/peri-ictal period with at least 14 days washout between doses.

Each subject received a single dose of DBF based on the subject's age and weight.

Diazepam Buccal Film: Subjects received a single DBF dose determined by age and body weight during the interictal state and during the ictal/peri-ictal period with at least 14 days washout between doses.

Overall Number of Participants Analyzed 17 16
Measure Type: Count of Participants
Unit of Measure: Participants
2
  11.8%
1
   6.3%
Time Frame Adverse event data were collected from the time of informed consent through 14 days +/- 2 days after dosing
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Interictal Period (Period A) Ictal/Peri-ictal Period (Period B)
Hide Arm/Group Description

Each subject received a single dose of DBF based on the subject's age and weight.

Diazepam Buccal Film: Subjects received a single DBF dose determined by age and body weight during the interictal state and during the ictal/peri-ictal period with at least 14 days washout between doses.

Each subject received a single dose of DBF based on the subject's age and weight.

Diazepam Buccal Film: Subjects received a single DBF dose determined by age and body weight during the interictal state and during the ictal/peri-ictal period with at least 14 days washout between doses.

All-Cause Mortality
Interictal Period (Period A) Ictal/Peri-ictal Period (Period B)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/17 (0.00%)      2/16 (12.50%)    
Hide Serious Adverse Events
Interictal Period (Period A) Ictal/Peri-ictal Period (Period B)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/17 (0.00%)      2/16 (12.50%)    
Infections and infestations     
Pneumonia  1  0/17 (0.00%)  0 1/16 (6.25%)  2
Nervous system disorders     
Seizure  1  0/17 (0.00%)  0 1/16 (6.25%)  1
Seizure cluster  1  0/17 (0.00%)  0 1/16 (6.25%)  1
1
Term from vocabulary, MedDRA 19.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 4%
Interictal Period (Period A) Ictal/Peri-ictal Period (Period B)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/17 (52.94%)      7/16 (43.75%)    
Gastrointestinal disorders     
Vomiting  1 [1]  1/17 (5.88%)  4 0/16 (0.00%)  0
Nausea  1 [2]  1/17 (5.88%)  1 0/16 (0.00%)  0
General disorders     
Petit mal epilepsy  1 [3]  1/17 (5.88%)  1 1/16 (6.25%)  1
Pyexia  1 [4]  2/17 (11.76%)  2 1/16 (6.25%)  1
Infections and infestations     
Upper respiratory tract infection  1 [5]  2/17 (11.76%)  2 1/16 (6.25%)  1
Pneumonia  1 [6]  0/17 (0.00%)  0 1/16 (6.25%)  2
Sinusitis  1 [7]  1/17 (5.88%)  1 0/16 (0.00%)  0
Nervous system disorders     
Seizure  1 [8]  1/17 (5.88%)  1 3/16 (18.75%)  10
Dizziness  1  2/17 (11.76%)  2 0/16 (0.00%)  0
Generalized tonic-clonic seizure  1 [9]  0/17 (0.00%)  0 1/16 (6.25%)  5
Myoclonic epilepsy  1  0/17 (0.00%)  0 1/16 (6.25%)  2
Headache  1 [10]  1/17 (5.88%)  1 0/16 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1 [11]  1/17 (5.88%)  1 0/16 (0.00%)  0
Skin and subcutaneous tissue disorders     
Rash  1 [12]  0/17 (0.00%)  0 1/16 (6.25%)  1
1
Term from vocabulary, MedDRA 19.1
Indicates events were collected by systematic assessment
[1]
Vomiting
[2]
Nausea
[3]
Absence seizure
[4]
Fever
[5]
Upper respiratory infection
[6]
Pneumonia
[7]
Sinus infection
[8]
Seizure activity was reported as adverse event
[9]
Tonic-clonic seizure
[10]
Headache
[11]
Labored breathing
[12]
Rash on upper extremity and face
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Director of Clinical Operations
Organization: Aquestive Therapeutics
Phone: 908-941-1887
EMail: denis.scheper@aquestive.com
Layout table for additonal information
Responsible Party: Aquestive Therapeutics
ClinicalTrials.gov Identifier: NCT03222349    
Other Study ID Numbers: 160325
First Submitted: July 12, 2017
First Posted: July 19, 2017
Results First Submitted: January 28, 2021
Results First Posted: May 26, 2021
Last Update Posted: May 26, 2021