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

Sponsor
Aquestive Therapeutics (Industry)
Overall Status
Completed
CT.gov ID
NCT03222349
Collaborator
Syneos Health (Other), Covance (Industry)
24
10
2
30.3
2.4
0.1

Study Details

Study Description

Brief Summary

Open-label study to assess the pharmacokinetics of a single diazepam buccal film (DBF) dose in 3 age cohorts of pediatric patients with epilepsy (age 2-5 years, age 6-11 years, and age 12-16 years). Subjects in the 6-11 years and 12-16 years age cohorts received a single DBF dose during the interictal period (Period A) and ictal/peri-ictal period (Period B) with at least 14 days washout between doses. Subjects in the age 2-5 years age cohort received a single DBF dose only during the ictal/peri-ictal period (Period B).

Condition or Disease Intervention/Treatment Phase
  • Drug: Diazepam Buccal Film
Phase 2

Detailed Description

This was a Phase 2 multicenter, open-label, two-way study conducted in male and female pediatric subjects (aged 2 to 16 years) with a clinical diagnosis of epilepsy who were scheduled to be admitted to an Epilepsy Monitoring Unit (EMU), a general clinical research center (GCRC), or similar facility for evaluation of seizures and who complied with all remaining protocol eligibility criteria. To ensure that 16 to 18 subjects would complete the study across 3 age ranges (2 to 5 years, 6 to 11 years, and 12 to 16 years), a minimum of 24 subjects were to be enrolled (8 in each age cohort).

Subjects in the 6 to 11 years and 12 to 16 years age cohorts received a single dose of DBF during the interictal period (Period A) and ictal/peri-ictal period (Period B) with at least 14 days washout between doses. Subjects in the age 2 to 5 years age cohort received a single dose of DBF only during the ictal/peri-ictal period (Period B). DBF was provided in a range of doses from 5 to 17.5 mg. The appropriate dose of DBF was assigned on the basis of age and weight using an interactive web response system during check-in.

Period A (interictal administration): 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) 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.

Period B (ictal/peri-ictal administration): For the purpose of this study, the ictal state was defined as an ongoing clinically observable seizure or seizure activity as verified via EEG. The peri-ictal 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 monitoring, the peri-ictal 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 :
24 participants
Allocation:
Non-Randomized
Intervention Model:
Crossover Assignment
Intervention Model Description:
This was a multicenter study comprised of 2 treatment periods with a minimum 14 days between the 2 treatment periods.This was a multicenter study comprised of 2 treatment periods with a minimum 14 days 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 Pediatric Subjects With Epilepsy
Actual Study Start Date :
Aug 31, 2017
Actual Primary Completion Date :
Jan 28, 2020
Actual Study Completion Date :
Mar 11, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Interictal Period

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

Drug: 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.
Other Names:
  • DBSF
  • Experimental: Ictal/Peri-ictal Period

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

    Drug: 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.
    Other Names:
  • DBSF
  • Outcome Measures

    Primary Outcome Measures

    1. Area Under the Concentration Time Curve (AUC) 0 to 4 Hours Post-dose [Time 0 (dosing), 0.25, 0.5, 1, 1.5, 2, 4 hours post-dose]

      AUC calculated from time 0 (dosing) to 4 hours post-dose in both Period A (interictal administration) and Period B (ictal/peri-ictal administration)

    2. Area Under the Concentration Time Curve (AUC) From 0 to 2 Hours Post-dose [Time 0 (dosing), 0.25, 0.5, 1, 1.5, 2 hours post-dose]

      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)

    3. Time When Maximum Plasma Concentration Was Observed (Tmax) 0 to 2 Hours Post-dose [Time 0 (dosing), 0.25, 0.5, 1, 1.5, 2 hours post-dose]

      Tmax calculated from time 0 (dosing) to 2 hours post-dose in both Period A (interictal administration) and Period B (ictal/peri-ictal administration)

    4. Time When Maximum Plasma Concentration Was Observed (Tmax) 0-4 Hours Post-Dose [Time 0 (dosing), 0.25, 0.5, 1, 1.5, 2, 4 hours post-dose]

      Tmax calculated from dosing (Time 0) to 4 hours post-dose in both Period A (interictal administration) and Period B (ictal/peri-ictal administration)

    5. Observed Maximum Plasma Concentration (Cmax) 0-2 Hours [Time 0 (dosing), 0.25, 0.5, 1, 1.5, 2 hours post-dose]

      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)

    6. Observed Maximum Plasma Concentration (Cmax) From Time 0 (Dosing) to 4 Hours Post-dose [Time 0 (dosing), 0.25, 0.5, 1, 1.5, 2, 4 hours post-dose]

      Maximum observed plasma concentration from Time 0 to 4 hours post-dose in Period A (interictal administration) and Period B (ictal/peri-ictal administration)

    Secondary Outcome Measures

    1. 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. [Period A and Period B from the time of first attempt at DBF insertion to 15 minutes after insertion.]

      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?

    2. Usability of Diazepam Buccal Film: Unsuccessful Attempts [Period A and Period B from the time of first attempt at DBF insertion to 15 minutes after insertion.]

      Number of subjects with any unsuccessful DBF insertion attempts (All analyzed subjects with an unsuccessful attempt ultimately had a successful attempt at dosing)

    3. Usability Endpoint : Amount of Saliva That Exited the Mouth After DBF Dosing [Period A and Period B from the time of first attempt at DBF insertion to 15 minutes after insertion.]

      Estimation of the amount of saliva exiting the mouth in mL after DBF dosing in Period A and Period B

    4. Number of Subjects Who Swallowed DBF After Initial Insertion [Period A and Period B from the time of first attempt at DBF insertion to 15 minutes after insertion.]

      Number of subjects who swallowed DBF during Period A and/or Period B

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    2 Years to 16 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 have a clinical diagnosis of epilepsy (GTC seizures or focal seizures with impaired awareness) and were scheduled for admission to an Epilepsy Monitoring Unit (EMU), General Clinical Research Center (GCRC), or similar facility for evaluation.

    2. Male and female subjects between 2 and 16 years of age, inclusive.

    3. Subjects had a body weight of at least 6 kg and less than or equal to 111 kg.

    4. Subjects had an average frequency of at least 1 clinically apparent seizure every 3 days or ≥10 clinically apparent seizures per month, with alteration of consciousness as documented by reliable subject report, personal seizure diary records, and/or by seizure diaries dispensed at screening and verified prior to study entry.

    5. Female subjects of childbearing potential (i.e., were having periods, were not surgically sterile) must have had a negative serum pregnancy test (using Beta-hCG) at Screening and a negative urine pregnancy test on Study Day I prior to drug dosing. Female subjects of childbearing potential must have agreed to abstinence, have had a partner who was sterile, or have been practicing double barrier contraception or have been using an FDA-approved contraceptive (e.g., licensed hormonal or barrier methods) for greater than 2 months prior to screening visit, and must have committed to an acceptable form of birth control for the duration of the study and for 30 days after participation in the study.

    6. Male subjects with a female sexual partner of childbearing potential must have agreed to abstinence or to practice adequate birth control during the study, including at least 1 barrier method such a condom, diaphragm, or spermicide for more than 2 months prior to the screening visit, and must have committed to an acceptable form of birth control for the duration of the study and for 30 days after participation in the study. Also, male subjects must have agreed not to donate sperm during the study and for 90 days after the follow-up visit.

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

    8. Subject's parent or legally authorized representative must have been willing and able to complete informed consent and HIPAA authorization. Subjects must have been willing to give assent as required by the Institutional Review Board (IRB).

    9. Subject must have agreed to be available or subject's parent(s) or legally authorized representative(s) must have agreed to have the subject be available for both Treatment Periods and the Follow-up Visit, and must have been willing to comply with all required study procedures and adhere to all protocol requirements.

    10. Subject or subject's parent(s) or legally authorized representative(s) must have been able to comprehend and be informed of the nature of the study, as assessed by the Investigator.

    Exclusion Criteria:

    Potential subjects meeting any of the following criteria were excluded from participating in the study:

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

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

    3. Female subjects who were lactating, had a positive serum pregnancy test (β-hCG) at screening, or had a positive urine pregnancy test at Check-in for treatment periods.

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

    5. Subjects with recent history of suicide attempt (defined as an active, interrupted, or aborted attempt within the previous 5 years) or reported suicidal ideation in the previous 6 months as indicated by a positive response ("Yes") to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale performed at the screening 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 Investigator or designee and confirmed by Sponsor via written communication prior to subject enrollment. Abnormal laboratory results considered clinically significant by the Investigator or designee were to be evaluated by the Investigator in consultation with the Medical Monitor.

    7. Subjects with any clinically significant illness other than epilepsy within 30 days prior to study drug administration, as determined by the Investigator.

    8. Subjects with any significant physical or organ abnormality or other condition that would interfere with study participation or constitute a safety risk in the judgment of the Investigator.

    9. Subjects with any significant lesion of the oral cavity or having oral prophylactic or dental procedures within 30 days prior to study drug administration.

    10. Subjects with a QT interval corrected by Fridericia's formula (QTcF) >450 ms for males or QTcF >470 ms 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, phencyclidine, or a positive breath alcohol test. Subjects who tested positive for tetrahydrocannabinol (THC) at screening were excluded unless the Investigator was able to affirm in writing that the use of a medical marijuana product was part of the subject's treatment plan as recommended by a physician for treatment of a medical condition. In such case, the subject was to be allowed to continue with screening, and the medical marijuana product was to be recorded as a concomitant medication.

    1. Subjects with a known history or presence of any of the following:

    2. Substance abuse or dependence (including alcohol) within 1 year prior to first study drug administration

    3. Hypersensitivity or idiosyncratic reaction to diazepam, its excipients, sodium phosphates, and/or related substances, e.g., benzodiazepines

    4. Glaucoma (open or acute narrow angle)

    5. Severe allergic reactions (e.g., anaphylactic reactions, angioedema) to investigational product and excipients

    6. Subjects who had participated in another clinical trial or who had received an investigational drug within 30 days prior to study drug administration or 5 half-lives of the investigational drug-whichever was the longer period.

    7. Subjects with presence of mouth jewelry, dentures, oral implants, braces, or piercings in the mouth or tongue that, in the opinion of the Investigator, would have been likely to interfere with successful completion of the dosing procedure.

    8. Subjects with a blood or plasma donation within 30 days prior to screening.

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

    10. Consumption of alcohol within 48 hours before dosing; or 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 study drug administration.

    11. Use of any enzyme-modifying drugs, including strong inhibitors of cytochrome (CYP) 450 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 prior to study drug administration. (Barbiturates, carbamazepine, phenytoin, and other enzyme-modifying antiepileptic drugs (AEDs) that were medically needed were permitted.)

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

    13. Employee or immediate relative of an employee of Aquestive Therapeutics, any of its affiliates or partners, or Syneos Health.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Arizona Tucson Arizona United States 85719
    2 NW FL Clinical Research Group, LLC Gulf Breeze Florida United States 32561
    3 Children's St. Peters University Hospital New Brunswick New Jersey United States 08901
    4 Icahn School of Medicine at Mount Sinai New York New York United States 10029
    5 University of Rochester Rochester New York United States 14607
    6 Onsite Clinical Solutions LLC Charlotte North Carolina United States 28203
    7 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
    8 Dell Children's Medical Center Austin Texas United States 78723
    9 Austin Epilepsy Care Center Austin Texas United States 78758
    10 Virginia Commonwealth University Richmond Virginia United States 23298

    Sponsors and Collaborators

    • Aquestive Therapeutics
    • Syneos Health
    • Covance

    Investigators

    • Study Director: Gary Slatko, Aquestive Therapeutics

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Aquestive Therapeutics
    ClinicalTrials.gov Identifier:
    NCT03222349
    Other Study ID Numbers:
    • 160325
    First Posted:
    Jul 19, 2017
    Last Update Posted:
    May 26, 2021
    Last Verified:
    May 1, 2021
    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
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    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 Detail 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
    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

    Baseline Characteristics

    Arm/Group Title Safety Analysis Set
    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 Participants 24
    Age (Count of Participants)
    <=18 years
    24
    100%
    Between 18 and 65 years
    0
    0%
    >=65 years
    0
    0%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    14.0
    (1.58)
    Sex: Female, Male (Count of Participants)
    Female
    14
    58.3%
    Male
    10
    41.7%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    1
    4.2%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    5
    20.8%
    White
    14
    58.3%
    More than one race
    0
    0%
    Unknown or Not Reported
    4
    16.7%
    Region of Enrollment (Count of Participants)
    United States
    24
    100%
    Body Mass Index (kg/m^2) (kg/m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m^2]
    22.166
    (10.1980)

    Outcome Measures

    1. Primary Outcome
    Title Area Under the Concentration Time Curve (AUC) 0 to 4 Hours Post-dose
    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

    Outcome Measure Data

    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
    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.
    Measure Participants 8 8
    Mean (Standard Deviation) [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
    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

    Outcome Measure Data

    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)
    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.
    Measure Participants 8 8
    Mean (Standard Deviation) [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
    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

    Outcome Measure Data

    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)
    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.
    Measure Participants 8 8
    Mean (Standard Deviation) [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
    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

    Outcome Measure Data

    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)
    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.
    Measure Participants 8 8
    Mean (Standard Deviation) [hours]
    1.196
    (0.754)
    0.861
    (0.574)
    5. Primary Outcome
    Title Observed Maximum Plasma Concentration (Cmax) 0-2 Hours
    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

    Outcome Measure Data

    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)
    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.
    Measure Participants 8 8
    Mean (Standard Deviation) [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
    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

    Outcome Measure Data

    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
    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.
    Measure Participants 8 8
    Mean (Standard Deviation) [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.
    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.

    Outcome Measure Data

    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)
    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.
    Measure Participants 17 16
    Count of Participants [Participants]
    3
    12.5%
    1
    NaN
    8. Secondary Outcome
    Title Usability of Diazepam Buccal Film: Unsuccessful Attempts
    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.

    Outcome Measure Data

    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)
    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.
    Measure Participants 17 16
    Count of Participants [Participants]
    0
    0%
    4
    NaN
    9. Secondary Outcome
    Title Usability Endpoint : Amount of Saliva That Exited the Mouth After DBF Dosing
    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.

    Outcome Measure Data

    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)
    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.
    Measure Participants 17 16
    Participants with 0 mL saliva exiting the mouth
    13
    54.2%
    15
    NaN
    Participants with > 0 mL to ≤ 1 mL saliva exiting the mouth
    0
    0%
    1
    NaN
    Participants with > 1 mL to ≤ 2 mL saliva exiting the mouth
    2
    8.3%
    0
    NaN
    Participants with > 2 mL to ≤ 3 mL saliva exiting the mouth
    1
    4.2%
    0
    NaN
    Participants with no data reported or unknown
    1
    4.2%
    0
    NaN
    10. Secondary Outcome
    Title Number of Subjects Who Swallowed DBF After Initial Insertion
    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.

    Outcome Measure Data

    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)
    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.
    Measure Participants 17 16
    Count of Participants [Participants]
    2
    8.3%
    1
    NaN

    Adverse Events

    Time Frame Adverse event data were collected from the time of informed consent through 14 days +/- 2 days after dosing
    Adverse Event Reporting Description
    Arm/Group Title Interictal Period (Period A) Ictal/Peri-ictal Period (Period B)
    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 (%) # Events Affected / at Risk (%) # Events
    Total 0/17 (0%) 2/16 (12.5%)
    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%) 2/16 (12.5%)
    Infections and infestations
    Pneumonia 0/17 (0%) 0 1/16 (6.3%) 2
    Nervous system disorders
    Seizure 0/17 (0%) 0 1/16 (6.3%) 1
    Seizure cluster 0/17 (0%) 0 1/16 (6.3%) 1
    Other (Not Including Serious) Adverse Events
    Interictal Period (Period A) Ictal/Peri-ictal Period (Period B)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 9/17 (52.9%) 7/16 (43.8%)
    Gastrointestinal disorders
    Vomiting 1/17 (5.9%) 4 0/16 (0%) 0
    Nausea 1/17 (5.9%) 1 0/16 (0%) 0
    General disorders
    Petit mal epilepsy 1/17 (5.9%) 1 1/16 (6.3%) 1
    Pyexia 2/17 (11.8%) 2 1/16 (6.3%) 1
    Infections and infestations
    Upper respiratory tract infection 2/17 (11.8%) 2 1/16 (6.3%) 1
    Pneumonia 0/17 (0%) 0 1/16 (6.3%) 2
    Sinusitis 1/17 (5.9%) 1 0/16 (0%) 0
    Nervous system disorders
    Seizure 1/17 (5.9%) 1 3/16 (18.8%) 10
    Dizziness 2/17 (11.8%) 2 0/16 (0%) 0
    Generalized tonic-clonic seizure 0/17 (0%) 0 1/16 (6.3%) 5
    Myoclonic epilepsy 0/17 (0%) 0 1/16 (6.3%) 2
    Headache 1/17 (5.9%) 1 0/16 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 1/17 (5.9%) 1 0/16 (0%) 0
    Skin and subcutaneous tissue disorders
    Rash 0/17 (0%) 0 1/16 (6.3%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Director of Clinical Operations
    Organization Aquestive Therapeutics
    Phone 908-941-1887
    Email denis.scheper@aquestive.com
    Responsible Party:
    Aquestive Therapeutics
    ClinicalTrials.gov Identifier:
    NCT03222349
    Other Study ID Numbers:
    • 160325
    First Posted:
    Jul 19, 2017
    Last Update Posted:
    May 26, 2021
    Last Verified:
    May 1, 2021