Clinical trial NCT03428360: Safety and Tolerability Study of Diazepam Buccal Film (DBF) in Subjects With Epilepsy
Official title: An Open-Label, Safety and Tolerability Study of Chronic Intermittent Use of Diazepam Buccal Film (DBF) in Pediatric, Adolescent and Adult Subjects With Epilepsy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Epilepsy
Keywords: Seizure
Lead sponsor: Aquestive Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Syneos Health
name: Covance
First posted: 2018-02-09
Enrollment: 149
Sex: ALL
Minimum age (years): 2
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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).
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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.

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

Primary outcomes:
measure: Number of Subjects in the Safety Analysis Set With at Least 1 Treatment-emergent Adverse Event (TEAE)
timeFrame: Adverse events (AEs) were recorded from Day 1 through the last study contact (Month 7 telephone contact).
measure: Number of Subjects in Safety Analysis Set With Adverse Events of Special Interest (AESI)
timeFrame: AESIs were recorded from Day 1 through the last study contact (Month 7 telephone contact).
Secondary outcomes:
measure: Usability Assessment: Number of Use Occasions Where Difficulty in Opening the Outer Packaging Was Recorded.
timeFrame: Recorded in an electronic diary after each use of study drug, throughout the course of the study; approximately 6 months
measure: Usability Assessment: Ability to Open Foil Pouch on Each Use Occasion
timeFrame: Recorded in an electronic diary after each use of study drug, throughout the course of the study; approximately 6 months
measure: Usability Assessment: Ability to Remove Study Drug From Foil Pouch on Each Use Occasion
timeFrame: Recorded in an electronic diary after each use of study drug, throughout the course of the study; approximately 6 months
measure: Number of Occasions With Successful Insertion/Retention in Cheek
timeFrame: Recorded in an electronic diary after each use of study drug, throughout the course of the study; approximately 6 months
measure: Usability Assessment: Difficulty Inserting DBF Against the Buccal Mucosa (Number of Attempts to Insert Film for Each Use Occasion)
timeFrame: Recorded in an electronic diary after each use of study drug, throughout the course of the study; approximately 6 months
measure: Usability Assessment: Number of Occasions Where DBF Was Not Placed or Retained on the Inner Cheek Until Dissolution
timeFrame: Recorded in an electronic diary after each use of study drug, throughout the course of the study; approximately 6 months
measure: Usability Assessment: Reasons for Multiple Placement/Insertion Attempts During a Use Occasion
timeFrame: Recorded in an electronic diary after each use of study drug, throughout the course of the study; approximately 6 months
Other outcomes:
Locations:
city: Honolulu
country: United States
facility: Hawaii Neuroscience Center
state: Hawaii
city: Boise
country: United States
facility: Consultants in Epilepsy and Neurology, PLLC
state: Idaho
city: Voorhees
country: United States
facility: Clinical Research Center of New Jersey (CRCNJ)
state: New Jersey
city: Charlotte
country: United States
facility: OnSite Clinical Solutions LLC
state: North Carolina
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Austin
country: United States
facility: Austin Epilepsy Care Center
state: Texas
Study officials:
affiliation: Aquestive Therapeutics
name: Gary Slatko
role: STUDY_DIRECTOR
References: