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Trial record 4 of 7 for:    aquestive

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

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ClinicalTrials.gov Identifier: NCT03222349
Recruitment Status : Completed
First Posted : July 19, 2017
Results First Posted : May 26, 2021
Last Update Posted : May 26, 2021
Sponsor:
Collaborators:
Syneos Health
Covance
Information provided by (Responsible Party):
Aquestive Therapeutics

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).

Condition or disease Intervention/treatment Phase
Epilepsy Drug: Diazepam Buccal Film Phase 2

Detailed Description:

This was a Phase 2 multicenter, open-label, two-way study conducted in male and female pediatric subjects (aged 2 to 16 years) with a clinical diagnosis of epilepsy who were scheduled to be admitted to an Epilepsy Monitoring Unit (EMU), a general clinical research center (GCRC), or similar facility for evaluation of seizures and who complied with all remaining protocol eligibility criteria. To ensure that 16 to 18 subjects would complete the study across 3 age ranges (2 to 5 years, 6 to 11 years, and 12 to 16 years), a minimum of 24 subjects were to be enrolled (8 in each age cohort).

Subjects in the 6 to 11 years and 12 to 16 years age cohorts received a single dose of DBF 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 to 5 years age cohort received a single dose of DBF only during the ictal/peri-ictal period (Period B). DBF was provided in a range of doses from 5 to 17.5 mg. The appropriate dose of DBF was assigned on the basis of age and weight using an interactive web response system during check-in.

Period A (interictal administration): Subjects were considered to be in an interictal state if an interval of at least 3 hours had elapsed since any clinically observable postictal signs or symptoms (from the last observed seizure) and the subject had been seizure-free over this period. Subjects on electroencephalogram (EEG) monitoring were to be considered to be in an interictal state if an interval of at least 3 hours had elapsed since there were any postictal electrical findings on EEG.

Period B (ictal/peri-ictal administration): For the purpose of this study, the ictal state was defined as an ongoing clinically observable seizure or seizure activity as verified via EEG. The peri-ictal state was defined clinically as the subject's immediate postictal state following a generalized tonic-clonic (GTC) seizure or focal seizure with impaired awareness, and within 5 minutes following the last clonic jerk. For subjects on EEG monitoring, the peri-ictal state was to be defined as less than 5 minutes after cessation of seizure activity as verified via EEG.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: This was a multicenter study comprised of 2 treatment periods with a minimum 14 days between the 2 treatment periods.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter,Open Label Crossover Study to Assess the Pharmacokinetics and Safety of Diazepam Buccal Soluble Film (DBSF) in Pediatric Subjects With Epilepsy
Actual Study Start Date : August 31, 2017
Actual Primary Completion Date : January 28, 2020
Actual Study Completion Date : March 11, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Epilepsy
Drug Information available for: Diazepam

Arm Intervention/treatment
Experimental: Interictal Period
Each subject received a single dose of DBF based on the subject's age and weight.
Drug: Diazepam Buccal Film
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.
Other Name: DBSF

Experimental: Ictal/Peri-ictal Period
Each subject received a single dose of DBF based on the subject's age and weight.
Drug: Diazepam Buccal Film
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.
Other Name: DBSF




Primary Outcome Measures :
  1. Area Under the Concentration Time Curve (AUC) 0 to 4 Hours Post-dose [ Time Frame: Time 0 (dosing), 0.25, 0.5, 1, 1.5, 2, 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)

  2. Area Under the Concentration Time Curve (AUC) From 0 to 2 Hours Post-dose [ Time Frame: Time 0 (dosing), 0.25, 0.5, 1, 1.5, 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)

  3. Time When Maximum Plasma Concentration Was Observed (Tmax) 0 to 2 Hours Post-dose [ Time Frame: Time 0 (dosing), 0.25, 0.5, 1, 1.5, 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)

  4. Time When Maximum Plasma Concentration Was Observed (Tmax) 0-4 Hours Post-Dose [ Time Frame: Time 0 (dosing), 0.25, 0.5, 1, 1.5, 2, 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)

  5. Observed Maximum Plasma Concentration (Cmax) 0-2 Hours [ Time Frame: Time 0 (dosing), 0.25, 0.5, 1, 1.5, 2 hours post-dose ]
    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)

  6. Observed Maximum Plasma Concentration (Cmax) From Time 0 (Dosing) to 4 Hours Post-dose [ Time Frame: Time 0 (dosing), 0.25, 0.5, 1, 1.5, 2, 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)


Secondary Outcome Measures :
  1. 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. [ Time Frame: Period A and Period B from the time of first attempt at DBF insertion to 15 minutes after insertion. ]
    Was DBF spit out or blown out by the subject after adherence to the buccal mucosa or did the subject chew, talk or move the DBF prior to complete disintegration/dissolution?

  2. Usability of Diazepam Buccal Film: Unsuccessful Attempts [ Time Frame: Period A and Period B from the time of first attempt at DBF insertion to 15 minutes after insertion. ]
    Number of subjects with any unsuccessful DBF insertion attempts (All analyzed subjects with an unsuccessful attempt ultimately had a successful attempt at dosing)

  3. Usability Endpoint : Amount of Saliva That Exited the Mouth After DBF Dosing [ Time Frame: Period A and Period B from the time of first attempt at DBF insertion to 15 minutes after insertion. ]
    Estimation of the amount of saliva exiting the mouth in mL after DBF dosing in Period A and Period B

  4. Number of Subjects Who Swallowed DBF After Initial Insertion [ Time Frame: 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 during Period A and/or Period B



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   2 Years to 16 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Potential subjects meeting all of the following criteria may be included in the study:

  1. 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.
  2. Male and female subjects between 2 and 16 years of age, inclusive.
  3. Subjects had a body weight of at least 6 kg and less than or equal to 111 kg.
  4. 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.
  5. 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.
  6. 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.
  7. Subjects were currently receiving at least one antiepileptic medication.
  8. 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).
  9. 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.
  10. 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.

Exclusion Criteria:

Potential subjects meeting any of the following criteria were excluded from participating in the study:

  1. 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.
  2. 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.
  3. 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.
  4. Subjects with psychiatric disease that in the Investigator's judgment would prevent the subject's successful completion of the study.
  5. 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.
  6. 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.
  7. Subjects with any clinically significant illness other than epilepsy within 30 days prior to study drug administration, as determined by the Investigator.
  8. 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.
  9. Subjects with any significant lesion of the oral cavity or having oral prophylactic or dental procedures within 30 days prior to study drug administration.
  10. 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.
  11. 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.

  12. Subjects with a known history or presence of any of the following:

    1. Substance abuse or dependence (including alcohol) within 1 year prior to first study drug administration
    2. Hypersensitivity or idiosyncratic reaction to diazepam, its excipients, sodium phosphates, and/or related substances, e.g., benzodiazepines
    3. Glaucoma (open or acute narrow angle)
    4. Severe allergic reactions (e.g., anaphylactic reactions, angioedema) to investigational product and excipients
  13. Subjects who had participated in another clinical trial or who had received an investigational drug within 30 days prior to study drug administration or 5 half-lives of the investigational drug-whichever was the longer period.
  14. Subjects with presence of mouth jewelry, dentures, oral implants, braces, or piercings in the mouth or tongue that, in the opinion of the Investigator, would have been likely to interfere with successful completion of the dosing procedure.
  15. Subjects with a blood or plasma donation within 30 days prior to screening.
  16. Subjects not willing or unable to tolerate blood draws.
  17. Consumption of alcohol within 48 hours before dosing; or food or beverages containing grapefruit, star fruit, Seville oranges, and/or pomelo, or their derived products (e.g., fruit juice) within 10 days prior to study drug administration.
  18. Use of any enzyme-modifying drugs, including strong inhibitors of cytochrome (CYP) 450 enzymes (e.g., cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem, or HIV antivirals) and strong inducers of CYP enzymes (e.g., glucocorticoids, St. John's Wort, or rifampicin), in the previous 30 days prior to study drug administration. (Barbiturates, carbamazepine, phenytoin, and other enzyme-modifying antiepileptic drugs (AEDs) that were medically needed were permitted.)
  19. Use of any monoamine oxidase (MAO) inhibitors (e.g., phenelzine, tranylcypromine ), and/or phenothiazines (chlorpromazine) within 30 days prior to first study drug administration.
  20. Employee or immediate relative of an employee of Aquestive Therapeutics, any of its affiliates or partners, or Syneos Health.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03222349


Locations
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United States, Arizona
University of Arizona
Tucson, Arizona, United States, 85719
United States, Florida
NW FL Clinical Research Group, LLC
Gulf Breeze, Florida, United States, 32561
United States, New Jersey
Children's St. Peters University Hospital
New Brunswick, New Jersey, United States, 08901
United States, New York
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
University of Rochester
Rochester, New York, United States, 14607
United States, North Carolina
Onsite Clinical Solutions LLC
Charlotte, North Carolina, United States, 28203
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Dell Children's Medical Center
Austin, Texas, United States, 78723
Austin Epilepsy Care Center
Austin, Texas, United States, 78758
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Aquestive Therapeutics
Syneos Health
Covance
Investigators
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Study Director: Gary Slatko Aquestive Therapeutics
  Study Documents (Full-Text)

Documents provided by Aquestive Therapeutics:
Study Protocol  [PDF] March 6, 2020
Statistical Analysis Plan  [PDF] June 16, 2020

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Responsible Party: Aquestive Therapeutics
ClinicalTrials.gov Identifier: NCT03222349    
Other Study ID Numbers: 160325
First Posted: July 19, 2017    Key Record Dates
Results First Posted: May 26, 2021
Last Update Posted: May 26, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Aquestive Therapeutics:
interictal state
ictal/peri-ictal state
Additional relevant MeSH terms:
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Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Diazepam
Adjuvants, Anesthesia
Anticonvulsants
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hypnotics and Sedatives
Central Nervous System Depressants
Muscle Relaxants, Central
Neuromuscular Agents
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action