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Diazepam Buccal Film - Diastat Rectal Gel Crossover Study

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ClinicalTrials.gov Identifier: NCT03953820
Recruitment Status : Recruiting
First Posted : May 17, 2019
Last Update Posted : May 17, 2019
Sponsor:
Information provided by (Responsible Party):
Aquestive Therapeutics

Tracking Information
First Submitted Date  ICMJE April 26, 2019
First Posted Date  ICMJE May 17, 2019
Last Update Posted Date May 17, 2019
Actual Study Start Date  ICMJE April 13, 2019
Estimated Primary Completion Date July 31, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 15, 2019)
  • AUC 0-t [ Time Frame: 240 hours post-dose ]
    From time 0 to last non-zero concentration
  • AUC 0-inf [ Time Frame: 240 hours post-dose ]
    Area under concentration time curve, from time 0 to infinity (extrapolated)
  • Cmax [ Time Frame: 240 hours post-dose ]
    Maximum observed concentration
  • Tmax [ Time Frame: 240 hours post-dose ]
    Time when the maximal concentration is observed
  • T 1/2 el [ Time Frame: 240 hours post-dose ]
    Terminal elimination half-life
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: May 15, 2019)
Safety-tolerability Treatment-emergent AEs from single doses of DBF and DRG administered to adult male and female subjects [ Time Frame: 10 days following the last study drug administration ]
Treatment-emergent AEs from single doses of DBF and DRG administered to adult male and female subjects on a stable concomitant regimen of AEDs under fed conditions
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Diazepam Buccal Film - Diastat Rectal Gel Crossover Study
Official Title  ICMJE A Randomized, Open-Label, 2-Way Crossover Study to Evaluate Single Doses of Diazepam Buccal Film (DBF) (Aquestive Therapeutics) Compared With Diastat® Rectal Gel (Valeant Pharmaceuticals North America) In Adult Male and Female Subjects on A Concomitant Regimen of Antiepileptic Drugs (AED) For the Treatment of Epilepsy
Brief Summary Randomized, multiple centers, single-dose, open-label, two-period, two-treatment, two-sequence crossover study under fed conditions. Each subject will receive both DBF and DRG administered according to weight category. DBF will be administered according to the currently recommended dose regimen (derived by Aquestive from population PK modeling in healthy volunteers). DRG will be administered depending on weight category according to the current product labeling for Diastat®.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Epilepsy
Intervention  ICMJE
  • Drug: Diazepam
    Film administered according to weight
  • Drug: Diastat Rectal Gel
    Gel administered according to weight
Study Arms  ICMJE
  • Experimental: Diazepam Buccal Film
    Film administered on cheek
    Intervention: Drug: Diazepam
  • Active Comparator: Diastat AcuDial Rectal Gel
    Gel administered rectally
    Intervention: Drug: Diastat Rectal Gel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 15, 2019)
24
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 31, 2019
Estimated Primary Completion Date July 31, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female, smoker (no more than 25 cigarettes or equivalent daily) or non-smoker, ≥ 18 and ≤ 65 years of age, with body weight between 38 and 111 kg, inclusive. Potential subjects with weights in the range of 112 to 134 kg (247 - 249 pounds) may be allowed to participate in the study at the discretion of the Principal Investigator.
  2. On a stable and ongoing regimen of at least one AED for treatment of epilepsy. Stable regimen is defined as no change in AED regimen for at least 30 days before the first study drug administration and no change anticipated in the prescribed AED regimen over the course of study participation.
  3. Subjects must have a diagnosis of seizure disorder (any seizure type or frequency) under treatment with at least one AED.
  4. Healthy (except for seizure disorder), according to the medical history, ECG, vital signs, laboratory results and physical examination as determined by the Principal Investigator/Sub- Investigator.
  5. Clinical laboratory values within local laboratories acceptable ranges, unless values are deemed by the Principal Investigator/Sub-Investigator as "Not Clinically Significant".
  6. Ability to comprehend and be informed of the nature of the study, as assessed by clinic staff.
  7. Availability to volunteer for the entire study duration and willing to adhere to all protocol requirements.
  8. Agree not to have a tattoo or tongue or body piercing until the end of the study.
  9. Agree not to drive or operate heavy machinery if feeling dizzy or drowsy following drug administration until full mental alertness is regained.
  10. Subjects must be able and willing to remove denture or bracing at the time of dosing.
  11. Non-vasectomized male subjects must use two forms of medically accepted method of contraception with all sexual partners of childbearing potential during the study and for 111 days following the last dose of study drug. Medically accepted effective forms of contraception include:

    1. simultaneous use of a male condom and
    2. for the female partner, hormonal contraceptives (used since at least 4 weeks) or intrauterine contraceptive device (placed since at least 4 weeks) or diaphragm or cervical cap with intravaginally applied spermicide.
  12. Male subjects must be willing not to donate sperm until 111 days following the last study drug administration.
  13. Female subjects who are sexually active with a non-sterile male partner (sterile male partners are defined as men vasectomized since at least 6 months) must fulfill at least one of the following:

    1. Be surgically sterile for a minimum of 6 months;
    2. Post-menopausal for a minimum of 1 year;
    3. Agree to avoid pregnancy and use medically acceptable method of contraception as described below until at least 51 days after the last PK blood sample collection of the study. Medically acceptable methods of contraception include:

      • Intrauterine device (hormonal and non-hormonal) placed at least 4 weeks prior to first study drug administration,
      • Oral or transdermal hormonal contraceptives with a 28-days treatment cycle taken daily from at least 30 days prior to first study drug administration and with no expected change in dosage throughout the study, or • Double barrier method (male condom and intravaginally applied spermicide used simultaneously with diaphragm or cervical cap) starting at least 21 days prior to first study drug administration;
    4. agree to complete abstinence.

Exclusion Criteria:

  1. Clinically significant abnormal laboratory test results found during medical screening.
  2. Positive pregnancy test at screening.
  3. Known presence of any clinically significant: hepatic (e.g. hepatic impairment), renal/genitourinary (renal impairment, kidney stones), gastrointestinal (e.g. ulcerative colitis, ileus, partial or complete intestinal blockage, appendicitis), cardiovascular (e.g. uncontrolled hypertension), cerebrovascular, pulmonary, endocrine (controlled diabetes is acceptable), immunological, musculoskeletal, neurological (other than known seizure disorder), 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.
  4. Presence of any clinically significant gastrointestinal pathology (e.g. chronic diarrhea, inflammatory bowel disease), unresolved gastrointestinal symptoms (e.g. diarrhea, vomiting), or other conditions known to interfere with the absorption, distribution, metabolism or excretion of the study drug experienced within 7 days prior to first study drug administration, as determined by the Principal Investigator/Sub-Investigator.
  5. Any clinically significant rectal abnormality by history or physical examination, or any condition, for which, in the judgment of the Principal Investigator/Sub-Investigator, administration of rectal gel would cause a potential risk to the subject.
  6. Baseline levels of concomitant AED outside of the acceptable therapeutic range at screening.
  7. Presence of any clinically significant illness within 30 days prior to first study drug administration, as determined by the Principal Investigator/Sub-Investigator.
  8. Presence of any clinically significant physical or organ abnormality as determined by the Principal Investigator/Sub-Investigator.
  9. Presence of any clinically significant lesion of the oral cavity.
  10. Clinically significant ECG abnormalities (QTcF interval > 450 msec for males or QTcF interval > 470 msec for females) or vital sign abnormalities (systolic blood pressure lower than 90 or over 160 mmHg, diastolic blood pressure lower than 50 or over 100 mmHg, or heart rate less than 50 or over 100 bpm) at screening, unless deemed otherwise by the Principal Investigator/Sub-Investigator.
  11. A positive test result for HIV, Hepatitis B surface antigen, Hepatitis C.
  12. A positive test result for any of the following: drugs of abuse (amphetamines, methamphetamines, barbiturates, cocaine, opiates, phencyclidine, tetrahydrocannabinol,MDMA, methadone, and benzodiazepines, except where a positive test is consistent with a stable regimen of a prescribed medication) and alcohol breath test.
  13. Known history or presence of:

    1. Alcohol abuse or dependence within one year prior to screening;
    2. Drug abuse or dependence;
    3. Hypersensitivity or idiosyncratic reaction to diazepam, DBF excipients, DRG excipients;
    4. Glaucoma (open or acute narrow angle);
    5. Food allergies and/or presence of any dietary restrictions that, in the judgment of the investigator or the Sponsor, would interfere with study procedures or the subject's safe participation in the study.
    6. Severe allergic reactions (e.g. anaphylactic reactions, angioedema).
  14. Intolerance to and/or difficulty with blood sampling through venipuncture.
  15. Individuals who have donated, in the days prior to first study drug administration:

    • 50-499 mL of blood in the previous 30 days;
    • 500 mL or more in the previous 56 days.
  16. Donation of plasma by plasmapheresis within 7 days prior to first study drug administration.
  17. Individuals who have participated in another clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to the first dosing, administration of a biological product in the context of a clinical research study within 90 days prior to the first dosing, or concomitant participation in an investigational study including an investigational study involving no drug or device administration.
  18. Use of diazepam within 30 days prior to first study drug administration.
  19. Use of strong inhibitors of CYP enzymes (e.g. cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem and HIV antivirals) in the previous 30 days before first study drug administration. Use of strong inducers of CYP enzymes (e.g. barbiturates, carbamazepine, glucocorticoids, phenytoin, St. John´s Wort, and rifampicin) and AEDs known to induce CYP enzymes are permitted provided that the regimen of such drugs is stable (taken at least q.d. on a regular basis) within 30 days prior to first study drug administration and until 10 days after last study drug administration.
  20. Use of any prescription medication (other than non-systemic topical products) within 30 days prior to first study drug administration. A prescription drug (other than diazepam and any benzodiazepines, phenothiazines, and strong inhibitors of CYP enzymes) that is part of a stable drug regimen (taken at least q.d. on a regular basis) is allowed if taken from at least 30 days prior to the first study drug administration and if there is no expected change in dosage throughout the study.
  21. Use of any OTC medications (other than spermicidal/barrier contraceptive products and nonsystemic topical products), within 30 days prior to first study drug administration. OTC drugs that is part of a stable drug regimen (taken at least q.d. on a regular basis) is allowed if taken from at least 30 days prior to the first study drug administration and if there is no expected change in dosage throughout the study.
  22. Natural health products (including oral multivitamins, herbal and/or dietary supplements and/or teas) from 30 days pre-dose until after the last PK blood sample collection of each period.
  23. Use of marijuana and THC containing products within 3 months prior to screening unless such products are a part of the subject's stable antiepileptic regimen.
  24. Use of any monoamine oxidase (MAO) inhibitors (e.g. phenelzine, tranylcypromine), phenothiazines (e.g. chlorpromazine) within 30 days prior to first study drug administration.
  25. Female subjects who have taken oral or transdermal hormonal contraceptives (other than 28-days treatment cycle contraceptive products) within 30 days prior to first drug administration, or have used an implanted, injected, or intravaginal contraceptive within 6 months prior to first drug administration.
  26. Individuals having undergone any major surgery within 6 months prior to the start of the study, unless deemed otherwise by Principal Investigator/Sub-Investigator.
  27. Presence of mouth jewellery, dentures, 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
  28. Dental procedures performed within 14 days of dosing or dental procedures scheduled to occur during study duration.
  29. Unable or unwilling to provide informed consent.
  30. Have had a tattoo or body/mouth piercing within 30 days prior to first study drug administration.
  31. Employee or immediate relative of an employee of Aquestive Therapeutics, any of its affiliates or partners, of the CRO, or the clinical site.
  32. Breast-feeding subject.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Clinical Operations Manager 908-941-1914 clinicaltrials@aquestive.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03953820
Other Study ID Numbers  ICMJE 180323
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Aquestive Therapeutics
Study Sponsor  ICMJE Aquestive Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Gary Slatko, MD Aquestive Therapeutics
PRS Account Aquestive Therapeutics
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP