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

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ClinicalTrials.gov Identifier: NCT03428360
Recruitment Status : Recruiting
First Posted : February 9, 2018
Last Update Posted : March 14, 2018
Sponsor:
Collaborators:
Inventiv Health
Covance
Information provided by (Responsible Party):
Aquestive Therapeutics

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.

Condition or disease Intervention/treatment Phase
Epilepsy Drug: Diazepam Buccal Soluble Film 5, 7.5,10, 12.5, and 15 mg Phase 3

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
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
Official Title: 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
Actual Study Start Date : January 23, 2018
Estimated Primary Completion Date : April 30, 2019
Estimated Study Completion Date : June 7, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Epilepsy Seizures
Drug Information available for: Diazepam

Arm Intervention/treatment
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, and 15 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.
Drug: Diazepam Buccal Soluble Film 5, 7.5,10, 12.5, and 15 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




Primary Outcome Measures :
  1. 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

  2. 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)

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03428360


Contacts
Contact: Carla Product Development Manager, BS Pharmacy 908-941-1896 cbuan@aquestive.com

Locations
United States, Hawaii
Hawaii Neuroscience Center Recruiting
Honolulu, Hawaii, United States, 96187
Contact: Kore Liow, MD    808-261-4476    kliow@hawaiineuroscience.com   
Principal Investigator: Kore Liow, MD         
Sub-Investigator: Patricia Borman, MD         
Sub-Investigator: Allison Przekop, DO         
Sub-Investigator: Paul Adapon III         
United States, Idaho
Consultants in Epilepsy and Neurology, PLLC Recruiting
Boise, Idaho, United States, 83702
Contact: Robert T Wechsler, MD    208-275-8585    rtw@idahoepilepsy.com   
Principal Investigator: Robert T Wechsler, MD         
Sub-Investigator: Jessica Bishop, PA-C         
Sub-Investigator: Lisa Gravett, RN         
United States, New Jersey
Clinical Research Center of New Jersey (CRCNJ) Recruiting
Voorhees, New Jersey, United States, 08043
Contact: Mark Mintz, MD    856-346-0005 ext 1101    mmintz@cnnh.org   
Principal Investigator: Mark Mintz, MD         
Sub-Investigator: Roger M Kurlan, MD         
United States, North Carolina
OnSite Clinical Solutions LLC Recruiting
Charlotte, North Carolina, United States, 28203
Contact: Robert A Nahouraii, MD    800-785-3150    rnahouraiiMD@onsiteclinical.com   
Principal Investigator: Robert A Nahouraii, MD         
Sub-Investigator: Kurt R Washburn, MD         
Sub-Investigator: Kayla "Brooke" Withers         
Sub-Investigator: Syed Mehdi         
United States, Pennsylvania
Hospital of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Michael A Gelfand, MD    215-349-5166    michael.gelfand@uphs.upenn.edu   
Principal Investigator: Michael A Gelfand, MD         
Sub-Investigator: Ashlie Jefferson         
Sub-Investigator: Meryl Lozano         
Sub-Investigator: Kelly Ca         
Sub-Investigator: Lee Jeon         
United States, Texas
Austin Epilepsy Care Center Recruiting
Austin, Texas, United States, 78758
Contact: Sami Aboumatar    515-339-8831    sami@austinepilepsy.com   
Sponsors and Collaborators
Aquestive Therapeutics
Inventiv Health
Covance

Responsible Party: Aquestive Therapeutics
ClinicalTrials.gov Identifier: NCT03428360     History of Changes
Other Study ID Numbers: 42-1703
First Posted: February 9, 2018    Key Record Dates
Last Update Posted: March 14, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
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:
Seizure

Additional relevant MeSH terms:
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Diazepam
Adjuvants, Anesthesia
Anticonvulsants
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hypnotics and Sedatives
Central Nervous System Depressants
Muscle Relaxants, Central
Neuromuscular Agents
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action