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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03428360
Recruitment Status : Active, not recruiting
First Posted : February 9, 2018
Last Update Posted : June 26, 2020
Sponsor:
Collaborators:
Syneos Health
Covance
Information provided by (Responsible Party):
Aquestive Therapeutics

Tracking Information
First Submitted Date  ICMJE December 18, 2017
First Posted Date  ICMJE February 9, 2018
Last Update Posted Date June 26, 2020
Actual Study Start Date  ICMJE January 23, 2018
Estimated Primary Completion Date October 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 31, 2020)
  • Number of Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Through study completion, an average of 1 year ]
    Any symptom, physical sign, syndrome or disease that either emerges during the study or, if present at screening, worsens during the study, regardless of the suspected cause of the event
  • Number of TEAEs judged to be related to the study drug (Diazepam Buccal Soluble Film) [ Time Frame: Through study completion, an average of 1 year ]
    Any symptom, physical sign, syndrome or disease that either emerges during the study, or if present at screening, worsens during the study, judged to be due to study drug (DBSF)
  • Number of Serious Adverse Events (SAEs) [ Time Frame: Through study completion, an average of 1 year ]
    An adverse event that is fatal, life threatening, results in inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or is a congenital anomaly/birth defect
  • Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Through study completion, an average of 1 year ]
    Instrument to assess suicidal behavior and ideation on a scale with 5 yes or no questions plus intensity and assessment of suicidal behavior
  • Blood Pressure [ Time Frame: Through study completion, an average of 1 year ]
    Measured after the subject has been resting in the sitting position for at least 5 minutes. Blood pressure measurements are to be taken in the same arm (if possible) for the duration of the study.
  • Oral mucosa examination [ Time Frame: Through study completion, an average of 1 year ]
    Pathological change in oral mucosa as measured by an illuminated oral examination
  • Gustatory sense test [ Time Frame: Through study completion, an average of 1 year ]
    Gustatory sense changes as measured by the National Institutes of Health (NIH) toolbox regional taste intensity test
  • Heart Rate [ Time Frame: Through study completion, an average of 1 year ]
    Measured after the subject has been resting in the sitting position for at least 5 minutes.
  • Respiratory Rate [ Time Frame: Through study completion, an average of 1 year ]
    Measured after the subject has been resting in the sitting position for at least 5 minutes.
  • Oral Temperature [ Time Frame: Through study completion, an average of 1 year ]
    Measured after the subject has been resting in the sitting position for at least 5 minutes.
  • Clinical laboratory tests [ Time Frame: At each onsite visit through study completion (Visits 1-5) ]
    Hematology, serum chemistry, urinalysis; urine and serum pregnancy test (FOCP)
Original Primary Outcome Measures  ICMJE
 (submitted: February 8, 2018)
  • Number of Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Through study completion, an average of 1 year ]
    Any symptom, physical sign, syndrome or disease that either emerges during the study or, if present at screening, worsens during the study, regardless of the suspected cause of the event
  • Number of TEAEs judged to be related to the study drug (Diazepam Buccal Soluble Film) [ Time Frame: Through study completion, an average of 1 year ]
    Any symptom, physical sign, syndrome or disease that either emerges during the study, or if present at screening, worsens during the study, judged to be due to study drug (DBSF)
  • Number of Serious Adverse Events (SAEs) [ Time Frame: Through study completion, an average of 1 year ]
    An adverse event that is fatal, life threatening, results in inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or is a congenital anomaly/birth defect
  • Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Through study completion, an average of 1 year ]
    Instrument to assess suicidal behavior and ideation on a scale with 5 yes or no questions plus intensity and assessment of suicidal behavior
  • Blood Pressure [ Time Frame: Through study completion, an average of 1 year ]
    Measured after the subject has been resting in the sitting position for at least 5 minutes. Blood pressure measurements are to be taken in the same arm (if possible) for the duration of the study.
  • Oral mucosa examination [ Time Frame: Through study completion, an average of 1 year ]
    Pathological change in oral mucosa as measured by an illuminated oral examination
  • Gustatory sense test [ Time Frame: Through study completion, an average of 1 year ]
    Gustatory sense changes as measured by the National Institutes of Health (NIH) toolbox regional taste intensity test
  • Heart Rate [ Time Frame: Through study completion, an average of 1 year ]
    Measured after the subject has been resting in the sitting position for at least 5 minutes.
  • Respiratory Rate [ Time Frame: Through study completion, an average of 1 year ]
    Measured after the subject has been resting in the sitting position for at least 5 minutes.
  • Oral Temperature [ Time Frame: Through study completion, an average of 1 year ]
    Measured after the subject has been resting in the sitting position for at least 5 minutes.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 8, 2018)
  • Pediatric Quality of Life Inventory (PedsQL) [ Time Frame: Study visits 2-7 (day 1, day 5-14, month 3, month 6, month 9, and month 12) ]
    Total score range 0-100 (higher score is better) Subscales include physical functioning, emotional functioning, social functioning, and school functioning.
  • Assessment of Usability by subject and/or caregiver to open packaging [ Time Frame: Study visits 1-6 (days -7 to -28, day 1, day 5-14, month 3, month 6, and month 9) ]
    The ability to open the packaging and remove the study drug
  • Assessment of Usability by subject and/or caregiver to correctly place study drug against buccal mucosa [ Time Frame: Study visits 1-6 (days -7 to -28, day 1, day 5-14, month 3, month 6, and month 9) ]
    Successful placement on the buccal mucosa
  • Oral cavity retention [ Time Frame: Study visits 2-7 (day 1, day 5-14, month 3, month 6, month 9, and month 12) ]
    The subject is assessed for if the DBSF is swallowed prior to dissolution and/or spit out or blown out by the subject after administration.
  • Quality of Life in Epilepsy (QOLIE-31-Pediatric) (version 2) [ Time Frame: Study visit 2-7 (day 1, day 5-14, month 3, month 6, month 9, and month 12) ]
    Quality of Life in Epilepsy Inventory - 31 item questionnaire comprising 7 subscales covering general and epilepsy-specific domains (18 years and older). Higher score indicates better health-related quality of life.
  • Quality of Life in Epilepsy (QOLIE-Adolescent-48) (version 1) [ Time Frame: Study visit 2-7 (day 1, day 5-14, month 3, month 6, month 9, and month 12) ]
    Quality of Life in Epilepsy Inventory - 48 question survey for adolescents comprising 8 subscales including epilepsy impact, memory/concentration, attitudes toward epilepsy, physical functioning, stigma, social support, school behavior, health perceptions, and a total summary score (11 - 17 years of age). Higher score indicates better health-related quality of life.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Tolerability Study of Diazepam Buccal Soluble Film (DBSF) in Subjects With Epilepsy
Official Title  ICMJE An Open-Label, Safety and Tolerability Study of Chronic Intermittent Use of Diazepam Buccal Soluble Film (DBSF) in Pediatric, Adolescent and Adult Subjects With Epilepsy
Brief Summary This Phase 3, multicenter, open-label study of chronic, intermittent use of study drug (DBSF) is designed to evaluate the safety and tolerability of the buccal formulation of diazepam in children, adolescents and adults with acute repetitive seizures.
Detailed Description

The Primary objective of the study is to assess the safety and tolerability of DBSF (study drug) administered to subjects with epilepsy for the treatment of seizures over a minimum 12-month period.

Secondary objectives of the study are;

  • To evaluate the usability of study drug as assessed by the ability of caregivers/subjects to administer study drug based on the Instructions for Use (IFU).
  • To evaluate the Quality of Life of the subjects during the study drug treatment period as assessed by age appropriate use of epilepsy scales [Pediatric Quality of Life Inventory (PedsQL), Quality of Life in Epilepsy Inventory (QOLIE) 39 and Quality of Life in Epilepsy Inventory (QOLIE) 49] over a minimum 12-month period.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
The study population will be male or female pediatric, adolescent and adult subjects with a clinical diagnosis of epilepsy and with bouts of increased seizure activity, Acute Repetitive Seizures (ARS), frequent breakthrough seizures, seizure clusters or cluster seizures.Subjects self-administer the study drug doses or with the caregiver's assistance if applicable to treat seizures, in response to the occurrence of the same characteristic events as they previously would with their usual rescue medication, e.g. Diastat® AcuDial™ or usual rescue therapy.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Epilepsy
Intervention  ICMJE Drug: Diazepam Buccal Soluble Film 5, 7.5,10, 12.5,15 or 17.5 mg
The subjects in this study will be administering DBSF 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 use the diazepam rectal gel or other rescue medication, without the presence of study staff.
Other Name: DBSF, DBF, Diazepam Buccal Film (Aquestive Therapeutics)
Study Arms  ICMJE Experimental: Subjects with Epilepsy
male or female pediatric, adolescent and adult subjects with a clinical diagnosis of epilepsy and with bouts of increased seizure activity, Acute Repetitive Seizures (ARS), frequent breakthrough seizures, seizure clusters or cluster seizures.Subjects with epilepsy self-administer Diazepam Buccal Soluble Film 5, 7.5,10, 12.5,15, or 17.5 mg or with the caregiver's assistance if applicable to treat seizures, in response to the occurrence of the same characteristic events as they previously would with their usual rescue medication, e.g. Diastat® AcuDial™ or usual rescue therapy.
Intervention: Drug: Diazepam Buccal Soluble Film 5, 7.5,10, 12.5,15 or 17.5 mg
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 31, 2020)
148
Original Estimated Enrollment  ICMJE
 (submitted: February 8, 2018)
120
Estimated Study Completion Date  ICMJE November 2020
Estimated Primary Completion Date October 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Female or male subject between the ages of 2 and 65 years of age, inclusive
  2. Written informed consent to participate in the study
  3. Subject has an established diagnosis of epilepsy either partial or generalized epilepsy with motor seizures with clear alteration of awareness, and while on a regimen of anti-epileptic medication(s), still experiences bouts of seizures (frequent break through seizures, e.g. ARS or seizure clusters) and who, in the opinion of the Investigator, may need benzodiazepine intervention for seizure control at least 1 time a month on average.
  4. Caregiver, if needed for subject, provides written informed consent and is able to administer study drug in the event of a seizure.
  5. Female subjects ≥12 years of age have a negative serum pregnancy test at screening. Female subjects of childbearing potential, (not surgically sterile or less than 2 years postmenopausal), must have a partner who is sterile, agrees to abstinence, be practicing double barrier contraception or using an FDA approved contraceptive (e.g., licensed hormonal or barrier methods) for greater than 2 months prior to screening visit and commit to an acceptable form of birth control for the duration of the study and for 30 days after the study
  6. No aspects of the medical history and/or the physical-neurological examination that at the judgment of the Investigator, in consultation with the Sponsor, will interfere with administration or absorption of study drug, or could evolve into a safety issue
  7. No clinically significant abnormal findings on the electrocardiogram (QTcF≤450 msec for males and QTcF≤470 msec for females)
  8. Subject and caregiver must be willing to comply with all study visits and all required study procedures

Exclusion Criteria:

  1. A history of clinically significant gastrointestinal, renal/genitourinary, hepatic, hematologic, dermatologic, endocrine, oncologic, pulmonary, immunologic, psychiatric, or cardiovascular disease, or any other clinically significant abnormalities, such as physical examination, vital signs, laboratory tests or ECG at Screening or Baseline which in the opinion of the investigator require further investigation or treatment or which may interfere with study procedures or safety or other medical conditions (e.g., cardiac, respiratory, gastrointestinal, psychiatric, renal disease) which are not adequately and stably controlled, or which in the opinion of the investigator(s) could affect the subject's safety or interfere with the study assessments or any other condition which, in the opinion of the Investigator, would jeopardize the safety of the subject
  2. Subject has had significant traumatic injury, major surgery or open biopsy within 30 days prior to study screening
  3. Subject with an active major depression or a past suicide attempt, or any suicidal ideation of 4, or 5 or any suicidal behavior in lifetime using C-SSRS. The pediatric C-SSRS should be used for subjects 6 to 11 years of age. The adult C-SSRS should be used for subjects ≥12 years of age. Note that this exclusion is only applicable to cognitive-appropriate subjects who are able to understand and complete the Suicide Rating Scale
  4. A history of allergic or adverse responses to diazepam or any other benzodiazepine
  5. Participation in a clinical trial other than MonoSol Rx Phase 2 studies 160325 and 160326 within 30 days prior to Day 0. Participation in an observational (non-interventional) study is not an exclusion, provided that there are no scheduling conflicts with this study. Received any other investigational medication (unless it can be documented that the subject received only placebo) or device within 8 weeks or 5 half-lives (whichever is longer) before assignment to study drug treatment
  6. Lactating female or positive serum pregnancy test (ß-hCG) at screening for female subjects ≥12 years of age
  7. Positive blood screen for HIV, HbSAg, or Hepatitis C, or a positive urine screen for alcohol or drugs of abuse, except marijuana use for medicinal indications. When marijuana is or was used for medicinal indications in the opinion of the Investigator, it is not considered as drug abuse and the subject can be enrolled in states where medical marijuana use is legal, even if the marijuana metabolites in the urine revealed as positive
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years to 65 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03428360
Other Study ID Numbers  ICMJE 42-1703
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Aquestive Therapeutics
Study Sponsor  ICMJE Aquestive Therapeutics
Collaborators  ICMJE
  • Syneos Health
  • Covance
Investigators  ICMJE
Study Director: Gary Slatko Aquestive Therapeutics
PRS Account Aquestive Therapeutics
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP