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

An Open-Label, Safety and Tolerability Study of Chronic Intermittent Use of Diazepam Buccal Film (DBF) in Pediatric, Adolescent and Adult Subjects With Epilepsy

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.

The Primary objective of the study is to assess the safety and tolerability of DBF (study drug) administered a minimum of 3 times to subjects with epilepsy for the treatment of seizures over a minimum 6-month period.

Secondary objectives:

• 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 (QoL) of the subjects during the study drug treatment period as assessed by use of age-appropriate epilepsy scales over a minimum 6-month period.

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