Safety and Tolerability Study of Diazepam Buccal Film (DBF) in Subjects With Epilepsy
Condition: Epilepsy
MeSH terms: Epilepsy
Intervention: Diazepam Buccal Soluble Film 5, 7.5,10, 12.5,15 or 17.5 mg with individual dose determined according to age and weight category
Intervention description: The subjects in this study administered DBF 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 used the diazepam rectal gel or other rescue medication, without the presence of study staff.
Intervention MeSH terms: Diazepam
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: The study population was male or female pediatric, adolescent, and adult subjects with a clinical diagnosis of epilepsy and with bouts of increased seizure activity, frequent breakthrough seizures, seizure clusters, or cluster seizures and who were on chronic, intermittent use of rescue medication (eg, Diastat AcuDial or other benzodiazepine).
Masking: None (Open Label)
Enrollment: 149.0
Sex: All
Minimum age: 2 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Seizure

Summary:

      This Phase 3, multicenter, open-label study of chronic, intermittent use of study drug (DBF)
      is designed to evaluate the safety and tolerability of the buccal formulation of diazepam in
      children, adolescents and adults with intermittent, stereotypic episodes of frequent seizure
      activity (eg, seizure clusters) that are distinct from the subject's usual seizure pattern.
    

Eligibility 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. Acute Repetitive Seizures (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 Columbia-Suicide
             Severity Rating Scale(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