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Trial record 73 of 146 for:    epilepsy AND Bethesda

Study to Assess the Pharmacokinetics and Safety of DBSF in Adult Subjects With Epilepsy

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ClinicalTrials.gov Identifier: NCT03179891
Recruitment Status : Recruiting
First Posted : June 7, 2017
Last Update Posted : September 20, 2018
Sponsor:
Collaborators:
inVentiv Health Clinical
Covance
Information provided by (Responsible Party):
Aquestive Therapeutics

Brief Summary:
The hypothesis of this study is that DBSF will be safe whether it is given when subjects are not experiencing seizures (Interictal Period A) or experiencing active seizures (ictal/peri-ictal Period B), and that Pharmacokinetic (PK) is not different during or in between the seizures.

Condition or disease Intervention/treatment Phase
Epilepsy Drug: Pharmacokinetics and Safety of Diazepam Buccal Soluble Film Phase 2

Detailed Description:

The primary objective of this study is to assess the comparative pharmacokinetics of DBSF in subjects with epilepsy under conditions where (a) they are not experiencing seizures (interictal Period A), and (b) when they are experiencing active seizures (ictal/peri-ictal Period B).

Secondary objectives include (a) evaluate the safety/tolerability of DBSF following single dose administration in subjects with epilepsy, (b) Evaluate the usability of DBSF in Period A and Period B.

This is a multi-center, open label, single-dose study that consists of 4 periods: Screening Period, Treatment Period A (interictal pharmacokinetic evaluation), Treatment Period B (ictal/peri-ictal pharmacokinetic evaluation), and Follow-up Period.

For the purposes of this study, the peri-ictal state is defined as the subject's immediate post-ictal state following a generalized tonic-clonic (GTC) seizure or focal seizure with impaired awareness up to 5 minutes following the last clonic jerk. This may also be defined as less than 5 minutes after cessation of the seizure (GTC or focal seizure with impaired awareness) as verified via EEG.

Subjects will have blood PK samples drawn at various time points and sent to the Central laboratory for Pharmacokinetic Assessments


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: This is a multi-center, open label, single-dose study that consists of 4 periods: Screening Period, Treatment Period A (interictal pharmacokinetic evaluation), Treatment Period B (ictal/peri-ictal pharmacokinetic evaluation), and Follow-up Period.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multi-Center, Open Label, Cross-Over Study to Assess the Pharmacokinetics and Safety of Diazepam Buccal Soluble Film (DBSF) in Adult Subjects With Epilepsy
Actual Study Start Date : August 31, 2017
Estimated Primary Completion Date : March 29, 2019
Estimated Study Completion Date : April 29, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Epilepsy
Drug Information available for: Diazepam

Arm Intervention/treatment
Interictal State
Pharmacokinetics and Safety of Diazepam Buccal Soluble Film during the interictal state in subjects with epilepsy
Drug: Pharmacokinetics and Safety of Diazepam Buccal Soluble Film
Comparative Pharmacokinetics and Safety of DBSF in subjects with epilepsy under conditions when they are not experiencing seizures (Interictal Period A) or when they are experiencing seizures (Ictal/peri-ictal Period B).
Other Name: DBSF

Ictal/peri-ictal state
Pharmacokinetics and Safety of Diazepam Buccal Soluble Film during the ictal/peri-ictal state in subjects with epilepsy
Drug: Pharmacokinetics and Safety of Diazepam Buccal Soluble Film
Comparative Pharmacokinetics and Safety of DBSF in subjects with epilepsy under conditions when they are not experiencing seizures (Interictal Period A) or when they are experiencing seizures (Ictal/peri-ictal Period B).
Other Name: DBSF




Primary Outcome Measures :
  1. Tmax Pharmacokinetic EndPoints [ Time Frame: -2 to 0, 0.25, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 192, 240 hours ]
    Observed time to reach maximum drug concentration (Tmax)

  2. Cmax Pharmacokinetic EndPoints [ Time Frame: -2 to 0, 0.25, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 192, 240 hours ]
    Observed Peak Drug Concentration (Cmax)

  3. Area under the Plasma Concentration curve Pharmacokinetic EndPoints [ Time Frame: -2 to 0, 0.25, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 192, 240 hours ]
    Area under the Plasma Concentration -time curve from time zero until the last measured time (AUC0-t) (Period A only)


Secondary Outcome Measures :
  1. Usability Endpoint - Successful insertion [ Time Frame: 0.167, 0.5 and 1 hours ]
    Number of successful attempts to insert the DBSF

  2. Usability Endpoint - Swallowing [ Time Frame: 0.167, 0.5 and 1 hours ]
    Number of times the DBSF is swallowed prior to dissolution

  3. Usability Endpoint - Lack of adherence [ Time Frame: 0.167, 0.5 and 1 hours ]
    Number of times the DBSF is spit out or blown out by patient after adherence to buccal mucosa

  4. Usability Endpoint - Saliva exiting the mouth [ Time Frame: 0.167, 0.5 and 1 hours ]
    Number of times saliva exits the mouth

  5. Usability Endpoint - Amount of saliva exiting the mouth [ Time Frame: 0.167, 0.5 and 1 hours ]
    The amount of saliva exiting the mouth



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
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 scheduled for admission to the institution's EMU, GCRC or similar facility for evaluation within 28 days.
  2. Male and female subjects between 18 to 65 years of age, inclusive.
  3. Subjects having a body weight of ≥ 40 kg to 111 kg.
  4. 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.
  5. 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.
  6. 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.
  7. Subjects are currently receiving at least one antiepileptic medication.
  8. Subjects or subject's legally authorized representative (LAR) must be willing and able to complete informed consent/assent and HIPAA authorization.
  9. Subjects must agree and must be willing to comply with all required study procedures while in the EMU or GCRC.
  10. Ability to comprehend and be informed of the nature of the study, as assessed by the PI or Sub-Investigator.
  11. Ability to consume standard meals.
  12. Availability to volunteer for the entire study duration and willing to adhere to all protocol requirements.

Exclusion Criteria:

Potential subjects meeting any of the following criteria will be excluded:

  1. 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.
  2. 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.
  3. Female subjects who are lactating or positive serum pregnancy test (ß-hCG) at screening for female subjects ≥12 years of age.
  4. Subjects with severe psychiatric disease that in the Investigator's judgment would prevent the patient's successful completion of the study.
  5. 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
  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 Principal Investigator/Sub-Investigator and confirmed by Sponsor via written communication prior to subject enrollment.
  7. Subjects with any clinically significant illness other than epilepsy within 30 days prior to first dosing, as determined by the Principal Investigator/Sub-Investigator.
  8. Subjects with any significant physical or organ abnormality as determined by the Principal Investigator/Sub-Investigator.
  9. Subjects with any significant lesion of the oral cavity or having oral prophylactic procedures within 30 days prior to first dosing.
  10. 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.
  11. Subjects with a positive test result for any of the following: drugs of abuse (amphetamines, cocaine, opiates, or phencyclidine), a positive breath alcohol test.
  12. 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
  13. 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.
  14. Blood or plasma donation within 30 days prior to Screening
  15. Subjects not willing or unable to tolerate blood draws.
  16. Subjects who have received any other dosage form of diazepam or benzodiazepines within 2 weeks prior to entering Period A or Period B.
  17. Consumption of alcohol within 48 hours before dosing and 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 first drug administration.
  18. Use of any enzyme-modifying drugs, including strong inhibitors of cytochrome P450 (CYP) 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 before first drug administration [barbiturates, carbamazepine, and phenytoin are allowed since these are common AEDs].
  19. Use of any monoamine oxidase (MAO) inhibitors (e.g. phenelzine, tranylcypromine), phenothiazines (chlorpromazine) within 30 days prior to first drug administration.
  20. Employee or immediate relative of an employee of the investigator, MonoSol Rx LLC, any of its affiliates or partners, or inVentiv 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): NCT03179891


Contacts
Contact: Frances Ekweonu 908-941-1914 fekweonu@aquestive.com

Locations
United States, Arizona
Arizona Health Sciences Center Recruiting
Tucson, Arizona, United States, 85724-5023
Contact: David M. Labiner, MD    520-626-2006      
United States, California
Rancho Research Institute Recruiting
Downey, California, United States, 90242
Contact: Hui Gong, MD    818-822-4916    hgong2@dhs.lacounty.gov   
United States, Connecticut
Yale University School of Medicine-Comprehensive Epilepsy Center Recruiting
New Haven, Connecticut, United States, 06520-8018
Contact: Kamil Detyniecki, MD    203-785-3865    kamil.detyniecki@yale.edu   
United States, Hawaii
Hawaii Pacific Neuroscience Recruiting
Honolulu, Hawaii, United States, 96817
Contact: Kore Liow, MD    808-261-4476    kliow@hawaiineuroscience.com   
United States, Maryland
Mid-Atlantic Epilepsy and Sleep Center Recruiting
Bethesda, Maryland, United States, 20817
Contact: Pavel Klein, M.B.    301-530-9744    kleinp@epilepsydc.com   
Contact: Diep Bui, M.D.         
United States, New Jersey
Saint Peter's University Hospital Recruiting
New Brunswick, New Jersey, United States, 08901
Contact: Carlos Lastra, MD    732-745-8600    clastra@saintpetersuh.com   
United States, New York
University of Rochester Medical Center Recruiting
Rochester, New York, United States, 14642
Contact: Trenton J. Tollefson, MD    507-273-4872    trenton_tollefson@urmc.rochester.edu   
United States, North Carolina
Onsite Clinical Solutions LLC Recruiting
Charlotte, North Carolina, United States, 28203
Contact: Robert Ataollah Nahouraii         
United States, Pennsylvania
Hospital of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Michael A. Gelfand, MD, PhD    215-349-5166    michael.gelfand@uphs.upenn.edu   
United States, Texas
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 Medical Center Recruiting
Richmond, Virginia, United States, 23219
Contact: Syndi A. Seinsefl, DO    804-828-0445    syndi.seinfeld@vcuhealth.org   
Sponsors and Collaborators
Aquestive Therapeutics
inVentiv Health Clinical
Covance

Responsible Party: Aquestive Therapeutics
ClinicalTrials.gov Identifier: NCT03179891     History of Changes
Other Study ID Numbers: 160326
First Posted: June 7, 2017    Key Record Dates
Last Update Posted: September 20, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Aquestive Therapeutics:
Interictal Period A
Icta/peri-ictal Period B

Additional relevant MeSH terms:
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