Study of Diazepam Buccal Film Administered in the Interictal and in the Ictal-Periictal States to Adults With Epilepsy
Condition: Epilepsy
MeSH terms: Epilepsy
Intervention: Diazepam Buccal Film 12.5 mg
Intervention description: All subjects received a single dose of DBF 12.5 mg during the interictal state and during the ictal/peri-ictal state with at least 14 days washout between the 2 treatment periods
Intervention MeSH terms: Diazepam
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Intervention model description: This was a multicenter, open-label study comprised of 2 treatment periods with a minimum 14 days washout between the 2 treatment periods.
Masking: None (Open Label)
Enrollment: 35.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Interictal; Ictal/peri-ictal

Summary:

      This Phase 2 open-label, two-way study was conducted in adult subjects with epilepsy who were
      on stable regimens of anti-epileptic drugs (AEDs) and who were admitted to an Epilepsy
      Monitoring Unit (EMU), General Clinical Research Center (GCRC), or similar facility for
      evaluation of their seizures. All subjects received a single DBF 12.5 mg dose during the
      Interictal State and a single DBF 12.5 mg dose during the Ictal/peri-ictal state with at
      least 14 days washout between the 2 doses.
    

Eligibility 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 (General Clinical
             Research Center) 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 (Anti-epileptic drugs)].

         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.