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

NCT03222349 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 160325
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 10

Brief Summary

Open-label study to assess the pharmacokinetics of a single diazepam buccal film (DBF) dose in 3 age cohorts of pediatric patients with epilepsy (age 2-5 years, age 6-11 years, and age 12-16 years). Subjects in the 6-11 years and 12-16 years age cohorts received a single DBF dose during the interictal period (Period A) and ictal/peri-ictal period (Period B) with at least 14 days washout between doses. Subjects in the age 2-5 years age cohort received a single DBF dose only during the ictal/peri-ictal period (Period B).

Conditions

Epilepsy

Keywords

interictal state; ictal/peri-ictal state

Outcome Measures

Primary Outcomes (6)

• Area Under the Concentration Time Curve (AUC) 0 to 4 Hours Post-dose

  AUC calculated from time 0 (dosing) to 4 hours post-dose in both Period A (interictal administration) and Period B (ictal/peri-ictal administration)

  Time 0 (dosing), 0.25, 0.5, 1, 1.5, 2, 4 hours post-dose

• Area Under the Concentration Time Curve (AUC) From 0 to 2 Hours Post-dose

  AUC calculated from time 0 (dosing) to 2 hours post-dose in both Period A (interictal administration) and Period B (ictal/peri-ictal administration)Period A (interictal administration) and Period B (ictal/peri-ictal administration)

  Time 0 (dosing), 0.25, 0.5, 1, 1.5, 2 hours post-dose

• Time When Maximum Plasma Concentration Was Observed (Tmax) 0 to 2 Hours Post-dose

  Tmax calculated from time 0 (dosing) to 2 hours post-dose in both Period A (interictal administration) and Period B (ictal/peri-ictal administration)

  Time 0 (dosing), 0.25, 0.5, 1, 1.5, 2 hours post-dose

• Time When Maximum Plasma Concentration Was Observed (Tmax) 0-4 Hours Post-Dose

  Tmax calculated from dosing (Time 0) to 4 hours post-dose in both Period A (interictal administration) and Period B (ictal/peri-ictal administration)

  Time 0 (dosing), 0.25, 0.5, 1, 1.5, 2, 4 hours post-dose

• Observed Maximum Plasma Concentration (Cmax) 0-2 Hours

  Maximum observed plasma concentration measured from Time 0 to 2 hours post-dose in Period A (interictal administration) and Period B (ictal/peri-ictal administration)

  Time 0 (dosing), 0.25, 0.5, 1, 1.5, 2 hours post-dose

• Observed Maximum Plasma Concentration (Cmax) From Time 0 (Dosing) to 4 Hours Post-dose

  Maximum observed plasma concentration from Time 0 to 4 hours post-dose in Period A (interictal administration) and Period B (ictal/peri-ictal administration)

  Time 0 (dosing), 0.25, 0.5, 1, 1.5, 2, 4 hours post-dose

Secondary Outcomes (4)

• Usability of Diazepam Buccal Film: Number of Subjects Who Spit Out/Moved/Chewed the Film After it Adhered (Stuck) to Buccal Mucosa During Period A and Period B.

  Period A and Period B from the time of first attempt at DBF insertion to 15 minutes after insertion.

• Usability of Diazepam Buccal Film: Unsuccessful Attempts

  Period A and Period B from the time of first attempt at DBF insertion to 15 minutes after insertion.

• Usability Endpoint : Amount of Saliva That Exited the Mouth After DBF Dosing

  Period A and Period B from the time of first attempt at DBF insertion to 15 minutes after insertion.

• Number of Subjects Who Swallowed DBF After Initial Insertion

  Period A and Period B from the time of first attempt at DBF insertion to 15 minutes after insertion.

Study Arms (2)

Interictal Period

EXPERIMENTAL

Each subject received a single dose of DBF based on the subject's age and weight.

Drug: Diazepam Buccal Film

Ictal/Peri-ictal Period

EXPERIMENTAL

Each subject received a single dose of DBF based on the subject's age and weight.

Drug: Diazepam Buccal Film

Interventions

Diazepam Buccal Film DRUG

Subjects received a single DBF dose determined by age and body weight during the interictal state and during the ictal/peri-ictal period with at least 14 days washout between doses.

Also known as: DBSF

Ictal/Peri-ictal Period; Interictal Period

Eligibility Criteria

• Age: 2 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Potential subjects meeting all of the following criteria may be included in the study:
• Subjects have a clinical diagnosis of epilepsy (GTC seizures or focal seizures with impaired awareness) and were scheduled for admission to an Epilepsy Monitoring Unit (EMU), General Clinical Research Center (GCRC), or similar facility for evaluation.
• Male and female subjects between 2 and 16 years of age, inclusive.
• Subjects had a body weight of at least 6 kg and less than or equal to 111 kg.
• Subjects had an average frequency of at least 1 clinically apparent seizure every 3 days or ≥10 clinically apparent seizures per month, with alteration of consciousness as documented by reliable subject report, personal seizure diary records, and/or by seizure diaries dispensed at screening and verified prior to study entry.
• Female subjects of childbearing potential (i.e., were having periods, were not surgically sterile) must have had a negative serum pregnancy test (using Beta-hCG) at Screening and a negative urine pregnancy test on Study Day I prior to drug dosing. Female subjects of childbearing potential must have agreed to abstinence, have had a partner who was sterile, or have been practicing double barrier contraception or have been using an FDA-approved contraceptive (e.g., licensed hormonal or barrier methods) for greater than 2 months prior to screening visit, and must have committed to an acceptable form of birth control for the duration of the study and for 30 days after participation in the study.
• Male subjects with a female sexual partner of childbearing potential must have agreed to abstinence or to practice adequate birth control during the study, including at least 1 barrier method such a condom, diaphragm, or spermicide for more than 2 months prior to the screening visit, and must have committed to an acceptable form of birth control for the duration of the study and for 30 days after participation in the study. Also, male subjects must have agreed not to donate sperm during the study and for 90 days after the follow-up visit.
• Subjects were currently receiving at least one antiepileptic medication.
• Subject's parent or legally authorized representative must have been willing and able to complete informed consent and HIPAA authorization. Subjects must have been willing to give assent as required by the Institutional Review Board (IRB).
• Subject must have agreed to be available or subject's parent(s) or legally authorized representative(s) must have agreed to have the subject be available for both Treatment Periods and the Follow-up Visit, and must have been willing to comply with all required study procedures and adhere to all protocol requirements.
• Subject or subject's parent(s) or legally authorized representative(s) must have been able to comprehend and be informed of the nature of the study, as assessed by the Investigator.

You may not qualify if:

• Potential subjects meeting any of the following criteria were excluded from participating in the study:
• Subjects with a progressive neurological disorder such as a brain tumor, demyelinating disease, or degenerative central nervous system (CNS) disease that was likely to progress in the 12 months after screening.
• Subjects with respiratory failure (or is at risk for respiratory failure) or other severe cardiorespiratory disease with New York Heart Association Class Ill or IV functional status, or who required supplemental oxygen.
• Female subjects who were lactating, had a positive serum pregnancy test (β-hCG) at screening, or had a positive urine pregnancy test at Check-in for treatment periods.
• Subjects with psychiatric disease that in the Investigator's judgment would prevent the subject's successful completion of the study.
• Subjects with recent history of suicide attempt (defined as an active, interrupted, or aborted attempt within the previous 5 years) or reported suicidal ideation in the previous 6 months as indicated by a positive response ("Yes") to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale performed at the screening 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 Investigator or designee and confirmed by Sponsor via written communication prior to subject enrollment. Abnormal laboratory results considered clinically significant by the Investigator or designee were to be evaluated by the Investigator in consultation with the Medical Monitor.
• Subjects with any clinically significant illness other than epilepsy within 30 days prior to study drug administration, as determined by the Investigator.
• Subjects with any significant physical or organ abnormality or other condition that would interfere with study participation or constitute a safety risk in the judgment of the Investigator.
• Subjects with any significant lesion of the oral cavity or having oral prophylactic or dental procedures within 30 days prior to study drug administration.
• Subjects with a QT interval corrected by Fridericia's formula (QTcF) \>450 ms for males or QTcF \>470 ms 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, phencyclidine, or a positive breath alcohol test. Subjects who tested positive for tetrahydrocannabinol (THC) at screening were excluded unless the Investigator was able to affirm in writing that the use of a medical marijuana product was part of the subject's treatment plan as recommended by a physician for treatment of a medical condition. In such case, the subject was to be allowed to continue with screening, and the medical marijuana product was to be recorded as a concomitant medication.
• Subjects with a known history or presence of any of the following:
• Substance abuse or dependence (including alcohol) within 1 year prior to first study drug administration

Sponsors & Collaborators

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

Study Sites (10)

University of Arizona

Tucson, Arizona, 85719, United States

Location

NW FL Clinical Research Group, LLC

Gulf Breeze, Florida, 32561, United States

Location

Children's St. Peters University Hospital

New Brunswick, New Jersey, 08901, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

University of Rochester

Rochester, New York, 14607, United States

Location

Onsite Clinical Solutions LLC

Charlotte, North Carolina, 28203, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Dell Children's Medical Center

Austin, Texas, 78723, United States

Location

Austin Epilepsy Care Center

Austin, Texas, 78758, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, 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

denis.scheper@aquestive.com

908-941-1887

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

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

Study Record Dates

• First Submitted: July 12, 2017
• First Posted: July 19, 2017
• Study Start: August 31, 2017
• Primary Completion: January 28, 2020
• Study Completion: March 11, 2020
• Last Updated: May 26, 2021
• Results First Posted: May 26, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)