Study of Diazepam Buccal Film Administered in the Interictal and in the Ictal-Periictal States to Adults With Epilepsy

NCT03179891 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 160326
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 11

Brief Summary

This Phase 2 open-label, two-way study was conducted in adult subjects with epilepsy who were on stable regimens of anti-epileptic drugs (AEDs) and who were admitted to an Epilepsy Monitoring Unit (EMU), General Clinical Research Center (GCRC), or similar facility for evaluation of their seizures. All subjects received a single DBF 12.5 mg dose during the Interictal State and a single DBF 12.5 mg dose during the Ictal/peri-ictal state with at least 14 days washout between the 2 doses.

Conditions

Epilepsy

Keywords

Interictal; Ictal/peri-ictal

Outcome Measures

Primary Outcomes (3)

• Tmax Pharmacokinetic EndPoints

  Observed time to reach maximum drug concentration (Tmax)

  -2 to 0, 0.25, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 192, 240 hours

• Cmax Pharmacokinetic EndPoints

  Observed Peak Drug Concentration (Cmax)

  -2 to 0, 0.25, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 192, 240 hours

• Area Under the Plasma Concentration Curve Pharmacokinetic EndPoints

  Area under the Plasma Concentration -time curve from time zero until the last measured time (AUC0-t)

  -2 to 0, 0.25, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 192, 240 hours

Secondary Outcomes (5)

• Usability Endpoint - Successful Insertion/Placement of the Diazepam Buccal Film (DBF) on First Attempt

  Subject was observed for 15 minutes after initial film placement/adhesion

• Usability Endpoint: Swallowing the Film Before Complete Disintegration/Dissolution

  Subject was observed for 15 minutes immediately following DBF placement/adhesion

• Usability Endpoint: Retention of Diazepam Buccal Film (DBF) From Placement to Complete Disintegration

  Subject was observed for 15 minutes immediately following DBF placement/adhesion

• Usability Endpoint: Exit of Saliva During the Time the Diazepam Buccal Film (DBF) Was Adhered to Buccal Mucosa

  Subject was observed for 15 minutes immediately following DBF placement/adhesion

• Usability Endpoint: Amount of Saliva That Exited the Mouth After Film Placement

  Subject was observed for 15 minutes immediately following DBF placement/adhesion

Study Arms (2)

Interictal Period

EXPERIMENTAL

All subjects received 12.5 mg DBF during the interictal state.

Drug: Diazepam Buccal Film 12.5 mg

Ictal/Peri-ictal Period

EXPERIMENTAL

All subjects received 12.5 mg DBF during the ictal/peri-ictal state.

Drug: Diazepam Buccal Film 12.5 mg

Interventions

Diazepam Buccal Film 12.5 mg DRUG

All subjects received a single dose of DBF 12.5 mg during the interictal state and during the ictal/peri-ictal state with at least 14 days washout between the 2 treatment periods

Also known as: DBF 12.5mg

Ictal/Peri-ictal Period; Interictal Period

Eligibility Criteria

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

You may qualify if:

• Potential subjects meeting all of the following criteria may be included in the study:
• Subjects scheduled for admission to the institution's EMU, GCRC (General Clinical Research Center) or similar facility for evaluation within 28 days.
• Male and female subjects between 18 to 65 years of age, inclusive.
• Subjects having a body weight of ≥ 40 kg to 111 kg.
• Subjects have a clinical diagnosis of epilepsy and are scheduled to be admitted to an Epilepsy Monitoring Unit (EMU) for extracranial video-Electroencephalogram (EEG) recording of a seizure event for evaluation of their epilepsy.
• Subjects have an average frequency of \> 1 seizure every 3 days or \> 10 seizures / month as documented by seizure diaries dispensed at the Screening Visit and verified prior to initiation of Period A or Period B.
• Female subjects have a negative serum pregnancy test at Screening. Female subjects of childbearing potential (i.e., not surgically sterile or 2 years postmenopausal) must have a negative pregnancy test at screening and a partner who is sterile, agree 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 participation in the study.
• Subjects are currently receiving at least one antiepileptic medication.
• Subjects or subject's legally authorized representative (LAR) must be willing and able to complete informed consent/assent and HIPAA authorization.
• Subjects must agree and must be willing to comply with all required study procedures while in the EMU or GCRC.
• Ability to comprehend and be informed of the nature of the study, as assessed by the PI or Sub-Investigator.
• Ability to consume standard meals.
• Availability to volunteer for the entire study duration and willing to adhere to all protocol requirements.

You may not qualify if:

• Potential subjects meeting any of the following criteria will be excluded:
• Subjects having a progressive neurological disorder such as brain tumor, demyelinating disease, or degenerative central nervous system (CNS) disease that is likely to progress in the next 12 months.
• Subjects having respiratory failure (or is at risk for respiratory failure) or other severe cardiorespiratory disease with New York Heart Association Class III or IV functional status, or requires supplemental oxygen.
• Female subjects who are lactating or positive serum pregnancy test (ß-hCG) at screening for female subjects ≥12 years of age.
• Subjects with severe psychiatric disease that in the Investigator's judgment would prevent the patient's successful completion of the study.
• Subjects who have an episode of status epilepticus, as determined by the Principal Investigator/Sub-Investigator, at any time during Period B (EMU, GCRC or similar facility Visit
• Subjects with known history or presence of any clinically significant hepatic (e.g. hepatic impairment), renal/genitourinary (renal impairment, kidney stones), psychiatric, dermatological or hematological disease or condition unless determined as not clinically significant by the Principal Investigator/Sub-Investigator and confirmed by Sponsor via written communication prior to subject enrollment.
• Subjects with any clinically significant illness other than epilepsy within 30 days prior to first dosing, as determined by the Principal Investigator/Sub-Investigator.
• Subjects with any significant physical or organ abnormality as determined by the Principal Investigator/Sub-Investigator.
• Subjects with any significant lesion of the oral cavity or having oral prophylactic procedures within 30 days prior to first dosing.
• Subjects with a QTc interval QTcF\>450 msec for males and QTcF\>470 msec for females on screening ECG, unless determined as not clinically significant by the Investigator.
• Subjects with a positive test result for any of the following: drugs of abuse (amphetamines, cocaine, opiates, or phencyclidine), a positive breath alcohol test.
• Subjects with a known history or presence of: a. Alcohol abuse or dependence within one year prior to first drug administration; b. Drug abuse or dependence; c. Hypersensitivity or idiosyncratic reaction to diazepam, its excipients, sodium phosphates; and/or related substances, e.g. benzodiazepines; d. Glaucoma (open or acute narrow angle); e. Severe allergic reactions (e.g. anaphylactic reactions, angioedema
• Subjects who have participated in another clinical trial or who received an investigational drug within 30 days prior to first drug administration or 5 half-lives of the investigational drug-whichever is the longer period.
• Blood or plasma donation within 30 days prior to Screening

Sponsors & Collaborators

• Aquestive Therapeutics: lead
• inVentiv Health Clinical: collaborator
• Covance: collaborator

Study Sites (11)

Arizona Health Sciences Center

Tucson, Arizona, 85724-5023, United States

Location

Rancho Research Institute

Downey, California, 90242, United States

Location

Yale University School of Medicine-Comprehensive Epilepsy Center

New Haven, Connecticut, 06520-8018, United States

Location

Hawaii Pacific Neuroscience

Honolulu, Hawaii, 96817, United States

Location

Mid-Atlantic Epilepsy and Sleep Center

Bethesda, Maryland, 20817, United States

Location

Saint Peter's University Hospital

New Brunswick, New Jersey, 08901, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, 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

Virginia Commonwealth University Medical Center

Richmond, Virginia, 23219, United States

Location

MeSH Terms

Conditions

Epilepsy

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Director of Clinical Operations
• Organization: Aquestive Therapeutics

clinicaltrials@aquestive.com

908-941-1900

Study Officials

• Gary Slatko

  Aquestive Therapeutics

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This was a multicenter, open-label study comprised of 2 treatment periods with a minimum 14 days washout between the 2 treatment periods.

Study Record Dates

• First Submitted: May 26, 2017
• First Posted: June 7, 2017
• Study Start: May 25, 2017
• Primary Completion: July 25, 2018
• Study Completion: December 21, 2018
• Last Updated: September 18, 2020
• Results First Posted: September 18, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)