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Assessment of Pharmacokinetics and Safety of Diazepam Buccal Soluble Film in Pediatric Patients (DBSF)

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ClinicalTrials.gov Identifier: NCT03222349
Recruitment Status : Recruiting
First Posted : July 19, 2017
Last Update Posted : January 11, 2019
Sponsor:
Collaborators:
inVentiv Health Clinical
Covance
Information provided by (Responsible Party):
Aquestive Therapeutics

Brief Summary:
The hypothesis of the study is that DBSF will be safe and tolerable in pediatric patients during the Interictal state (Period A) and the ictal/peri-ictal state (Period B) of Epilepsy, and pharmacokinetics will be the same during and in-between experiencing seizures.

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

Detailed Description:

This is a Multicenter , Open Label Crossover study to assess the Pharmacokinetics and Safety of Diazepam Buccal Soluble Film (DBSF) in Pediatric patients with Epilepsy.

The Primary objective of the study is to assess the pharmacokinetics of DBSF in pediatric patients with epilepsy in interictal State (Period A) and ictal/peri-ictal state (Period B).

Subjects are considered to be in interictal state if an interval of at least 3 hours has elapsed since any clinical observable postictal signs or symptoms (from the last observed seizure) and the subject has been seizure free over this period.

For the purposes of this study, the ictal state is defined as an ongoing clinically observable seizure or seizure activity as verified via EEG. The peri-ictal state is defined clinically as the subjects's immediate postictal state following a generalized tonic-clinic (GTC) seizure or focal seizure with impaired awareness , and within 5 minutes following the last clonic jerk.

The secondary objectives include a) Evaluate the safety/tolerability of DBSF in pediatric subjects with epilepsy. b) Evaluate the usability of DBSF.

The minimum study duration will be approximately 35 day, with a maximum of approximately 58 days , consisting of 1) screening period 2)Treatment Period A 3)Treatment Period B and 4) Follow up visit.

Blood samples will be drawn during the entire study for assessing the pharmacokinetics of the DBSF.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: This study uses a multicenter, open-label crossover design with the following periods : 1) Screening visit 2) Treatment Period A (Interictal DBSF dosing and Pharmacokinetic evaluation) 3)Treatment Period B (ictal/ peri-ictal DBSF dosing and pharmacokinetic evaluation) and 4) Follow up visit.
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
Estimated Primary Completion Date : September 30, 2019
Estimated Study Completion Date : November 24, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Epilepsy
Drug Information available for: Diazepam

Arm Intervention/treatment
Interictal State (Period A) of Epilepsy
Diazepam Buccal Soluble Film will be administered to epileptic patients during the icterictal state (Period A)
Drug: Diazepam Buccal Soluble Film
Subjects will receive a single dose of DBSF . DBSF is provided in a range of doses from 5 to 12.5 mg . The appropriate dose of DBSF will be assigned on the basis of age and weight using an interactive web response system (IWRS) during check-in for the subject's first treatment period.
Other Name: DBSF

ictal/peri-ictal state (Period B)
Diazepam Buccal Soluble Film will be administered to epileptic patients during the ictal/peri-ictal state (Period B)
Drug: Diazepam Buccal Soluble Film
Subjects will receive a single dose of DBSF . DBSF is provided in a range of doses from 5 to 12.5 mg . The appropriate dose of DBSF will be assigned on the basis of age and weight using an interactive web response system (IWRS) during check-in for the subject's first treatment period.
Other Name: DBSF




Primary Outcome Measures :
  1. Tmax Pharmacokinetic Endpoints [ Time Frame: 0.25,0.5,1,1.5,2 and 4 hours ]
    Observed time to reach maximum drug concentration (Tmax)

  2. Cmax Pharmacokinetic Endpoints [ Time Frame: 0.25,0.5,1,1.5,2 and 4 hours ]
    Observed peak drug concentration (Cmax)


Secondary Outcome Measures :
  1. Oral Safety Assessment- Mucosal Irritation [ Time Frame: 0.167 , 0.5, and 1 hour after complete disintegration/dissolution of the film ]
    The investigator will make an illumination-assisted visual inspection of the oral mucosa.



Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 17 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 se izures with impaired awareness) and are 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 17 years of age, inclusive.
  3. Subjects have a body weight of:0-6 kg and sl 11 kg.
  4. Subjects have an average frequency of:C:l clinically apparent seizures every 3 days or ≥10 clinically apparent seizures per month, with alteration ofconsciousness as documented by seizure diaries dispensed at the Screening Visit and verified prior to Treatment Period A or Treatment Period B.
  5. Female subjects of childbearing potential (i.e., are having periods, are not surgically sterile) must have a negative serum pregnancy test (ll-hCG) at Screening and a negative urine pregnancy test on Day I prior to drug dosing. Female subjects of childbearing potential must agree to abstinence, have a partner who is sterile, or be 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 commit to an acceptable form of birth control for the duration of the study and for 30 days after participation in the study.
  6. Subjects are currently receiving at least one antiepileptic medication.
  7. Subject's parent or legally authorized representative must be willing and able to complete informed consent and HIPAA authorization. Subjects must be willing to give assent as required by the !RB.
  8. Subject must agree to be available or subject's parent(s) or legally authorized representative must agree to have the subject be available for both Treatment Periods and the Follow-up Visit, and must be willing to comply with all required study procedures and adhere to all protocol requirements.
  9. Subject and/or subject's parent(s) or legally authorized representative must be 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 will be excluded:

  1. Subjects with a progressive neurological disorder such as a brain tumor, demyelinating disease, or degenerative central nervous system (CNS) disease that is likely to progress in the next 12 months.
  2. Subject has 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 requires supplemental oxygen.
  3. Female subjects who are lactating, have a positive serum pregnancy test (β-hCG) at screening, or have a positive urine pregnancy test at Check-in for treatment periods.
  4. Subjects with psychiatric disease (including Type 4 or Type 5 suicidal ideation on the C-SSRS) that in the Investigator's judgment would prevent the subject's successful completion of the study.
  5. 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 will be evaluated by the Investigator in consultation with the Medical Monitor.
  6. Subjects with any clinically significant illness other than epilepsy within 30 days prior to study drug administration, as determined by the Investigator.
  7. 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.
  8. Subjects with any significant lesion of the oral cavity or having oral prophylactic or dental procedures within 30 days prior to study drug administration.
  9. Subjects with a QTcF interval ≥450 msec for males or QTcF >470 msec for females on screening ECG, unless determined to be not clinically significant by the Investigator.

IO. Subjects with a positive test result for any of the following drugs of abuse:

amphetamines, cocaine, opiates, phencyclidine, or tetrahydrocannabinol [THC] (unless legal in state where subject resides and obtained with a prescription); or a positive breath alcohol test. 11. Subjects with a known history or presence of:

  1. Substance abuse or dependence (including alcohol) within one 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 12.Subjects who have participated in another clinical trial or who received an investigational drug within 30 days prior to study drug administration or 5 half-lives of the investigational drug-whichever is the longer period. 13. Subjects with presence of mouth jewelry, dentures, oral implants, braces, or piercings in the mouth or tongue that, in the opinion of the Principal Investigator, would be likely to interfere with successful completion of the dosing procedure. 14. Subjects with a blood or plasma donation within 30 days prior to Screening. 15. Subjects not willing or unable to tolerate blood draws. 16. 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. 17. 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 AEDs that are medically needed are permitted.) 18. Use of any monoamine oxidase (MAO) inhibitors (e.g., phenelzine, tranylcypromine ), phenothiazines (chlorpromazine) within 30 days prior to first study drug administration. 19. Employee or immediate relative of an employee of MonoSol Rx LLC, any of its affiliates or pattners, or inVentive 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


Contacts
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Contact: Frances Ekweonu 908-307-3549 fekweonu@aquestive.com

Locations
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United States, Arizona
University of Arizona Recruiting
Tucson, Arizona, United States, 85719
Contact: Sejal Jain         
United States, Florida
NW FL Clinical Research Group, LLC Recruiting
Gulf Breeze, Florida, United States, 32561
Contact: Weldon Mauney         
United States, New Jersey
Children's St. Peters University Hospital Recruiting
New Brunswick, New Jersey, United States, 08901
Contact: Carlos Lastra         
United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: Harriet Kang, MD    914-428-0529      
Principal Investigator: Harriet Kang, MD         
Sub-Investigator: Patricia McGoldrick, NP         
Sub-Investigator: Steven Wolf, MD         
University of Rochester Recruiting
Rochester, New York, United States, 14607
Contact: Inna Hughes         
United States, North Carolina
Onsite Clinical Solutions LLC Recruiting
Charlotte, North Carolina, United States, 28203
Contact: Robert Nahouraii         
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Dennis Dlugos         
United States, Texas
Dell Children's Medical Center Recruiting
Austin, Texas, United States, 78723
Contact: David Clarke         
Austin Epilepsy Care Center Recruiting
Austin, Texas, United States, 78758
Contact: Sami Aboumatar, MD    512-339-8831    sami@northaustinneuro.com   
United States, Virginia
Virginia Commonwealth University Recruiting
Richmond, Virginia, United States, 23298
Contact: Syndi Seinfeld         
Sponsors and Collaborators
Aquestive Therapeutics
inVentiv Health Clinical
Covance

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Responsible Party: Aquestive Therapeutics
ClinicalTrials.gov Identifier: NCT03222349     History of Changes
Other Study ID Numbers: 160325
First Posted: July 19, 2017    Key Record Dates
Last Update Posted: January 11, 2019
Last Verified: January 2019
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