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

NCT03428360 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 42-1703
• Study Type: interventional
• Target: 149
• Locations: 1 country
• Sites: 6

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.

Conditions

Epilepsy

Keywords

Seizure

Outcome Measures

Primary Outcomes (2)

• Number of Subjects in the Safety Analysis Set With at Least 1 Treatment-emergent Adverse Event (TEAE)

  A TEAE was defined as any adverse event with onset date on the day of or after administration of study drug including relationship and severity.

  Adverse events (AEs) were recorded from Day 1 through the last study contact (Month 7 telephone contact).

• Number of Subjects in Safety Analysis Set With Adverse Events of Special Interest (AESI)

  A.Oral irritation related AEs including but not limited to: buccal mucosal swelling, mouth ulceration, injuries to oral cavity (such as tongue or mucosal laceration, broken tooth, bleeding), erythema, stomatitis, gingivitis, xerostomia, staining, dysphagia, dysgeusia, burning, stinging, tingling. B. Abuse related AEs including euphoria, euphoric mood, feeling of relaxation, anger, dissociative effects, hallucinations, psychosis, changes in mood, impaired cognition, attention, psychomotor effects, inappropriate affect, overdose, and misuse. C. Other: Respiratory disorders, nervous system disorders

  AESIs were recorded from Day 1 through the last study contact (Month 7 telephone contact).

Secondary Outcomes (7)

• Usability Assessment: Number of Use Occasions Where Difficulty in Opening the Outer Packaging Was Recorded.

  Recorded in an electronic diary after each use of study drug, throughout the course of the study; approximately 6 months

• Usability Assessment: Ability to Open Foil Pouch on Each Use Occasion

  Recorded in an electronic diary after each use of study drug, throughout the course of the study; approximately 6 months

• Usability Assessment: Ability to Remove Study Drug From Foil Pouch on Each Use Occasion

  Recorded in an electronic diary after each use of study drug, throughout the course of the study; approximately 6 months

• Number of Occasions With Successful Insertion/Retention in Cheek

  Recorded in an electronic diary after each use of study drug, throughout the course of the study; approximately 6 months

• Usability Assessment: Difficulty Inserting DBF Against the Buccal Mucosa (Number of Attempts to Insert Film for Each Use Occasion)

  Recorded in an electronic diary after each use of study drug, throughout the course of the study; approximately 6 months

Study Arms (1)

Subjects with Epilepsy

EXPERIMENTAL

Male or female subjects between the ages of 2 and 65 years who had an established diagnosis of epilepsy exhibited by motor seizures with clear alteration of awareness, and while on a regimen of anti-epileptic medication(s), still experienced bouts of seizures (frequent breakthrough seizures, eg, seizure clusters) and who, in the opinion of the Investigator, could need benzodiazepine intervention for seizure control at least 1 time a month on average. Subjects must have been on at least 1 concomitant anti-epileptic drug at screening.

Drug: 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

Interventions

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 DRUG

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.

Also known as: DBF, Diazepam Buccal Film (Aquestive Therapeutics)

Subjects with Epilepsy

Eligibility Criteria

• Age: 2 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Female or male subject between the ages of 2 and 65 years of age, inclusive
• Written informed consent to participate in the study
• 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.
• Caregiver, if needed for subject, provides written informed consent and is able to administer study drug in the event of a seizure.
• 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
• 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
• No clinically significant abnormal findings on the electrocardiogram (QTcF≤450 msec for males and QTcF≤470 msec for females)
• Subject and caregiver must be willing to comply with all study visits and all required study procedures

You may not qualify if:

• 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
• Subject has had significant traumatic injury, major surgery or open biopsy within 30 days prior to study screening
• A history of allergic or adverse responses to diazepam or any other benzodiazepine
• Lactating female or positive serum pregnancy test (ß-hCG) at screening for female subjects ≥12 years of age
• 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

Sponsors & Collaborators

• Aquestive Therapeutics: lead
• Syneos Health: collaborator
• Covance: collaborator

Study Sites (6)

Hawaii Neuroscience Center

Honolulu, Hawaii, 96187, United States

Location

Consultants in Epilepsy and Neurology, PLLC

Boise, Idaho, 83702, United States

Location

Clinical Research Center of New Jersey (CRCNJ)

Voorhees Township, New Jersey, 08043, United States

Location

OnSite Clinical Solutions LLC

Charlotte, North Carolina, 28203, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Austin Epilepsy Care Center

Austin, Texas, 78758, United States

Location

MeSH Terms

Conditions

Epilepsy; Seizures

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Only those subjects who received at least one dose of DBF (130 out of 149) for a breakthrough seizure were included in the Safety Analysis Set.

Results Point of Contact

• Title: Clinical Project Manager
• Organization: Aquestive Therapeutics

cbuan@aquestive.com

9089411896

Study Officials

• Gary Slatko

  Aquestive Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: December 18, 2017
• First Posted: February 9, 2018
• Study Start: January 23, 2018
• Primary Completion: June 25, 2020
• Study Completion: June 25, 2020
• Last Updated: August 5, 2021
• Results First Posted: August 5, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)