Repeat-Dose Pharmacokinetics Study of NRL-1 in Epilepsy Subjects
Condition: Acute Repetitive Seizures
MeSH terms: Epilepsy; Seizures
Intervention: NRL-1
Intervention MeSH terms: Diazepam
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Masking description: open-label
Enrollment: 57.0
Sex: All
Minimum age: 6 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: epilepsy; seizure

Summary:

      This study evaluates the pharmacokinetic and safety of NRL-1 in epilepsy subjects. Subjects
      will receive a single intranasal dose of NRL-1 of either 5 mg, 10 mg, 15 mg or 20 mg and will
      be based on the subject's body weight.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male and female subjects between the ages of 6 and 65 years, inclusive.

          2. Written informed consent to participate in the study.

          3. Body mass index (BMI) not to exceed 35 kg/m², inclusive.

          4. Subject has a clinical diagnosis of Epilepsy and, in the opinion of the Investigator,
             may need benzodiazepine intervention for seizure control.

          5. Subjects having either partial or generalized Epilepsy with motor seizures or seizures
             with clear alteration of awareness are eligible for enrollment.

          6. Female subjects of childbearing potential, defined as having a menstrual cycle and who
             are not surgically sterile or less than two (2) years postmenopausal, must complete a
             pregnancy screen and agree to utilize one of the following forms of contraception
             during the trial and for 21 days after the last dose of study drug: abstinence,
             hormonal (oral, transdermal, implant, or injection), barrier (condom, diaphragm with
             spermicide), intrauterine device (IUD), or vasectomized partner (six months minimum).

          7. No clinically significant abnormal findings in the medical history, on the physical
             examination, ECG (corrected QT interval [QTcF] < 450 msec for males and QTcF < 470
             msec for females), or clinical laboratory results during screening.

          8. Subjects and caregivers must agree to return to the study site for all study visits
             and must be willing to comply with all required study procedures.

        Exclusion Criteria:

          1. Subject is undergoing intracranial EEG monitoring.

          2. A history of clinically significant gastrointestinal, renal, hepatic, neurologic,
             hematologic, endocrine, oncologic, pulmonary, immunologic, psychiatric, or
             cardiovascular disease, severe seasonal or non-seasonal allergies, nasal polyps or any
             nasal passage abnormality that could interfere with nasal spray administration, or any
             other condition which, in the opinion of the Investigator, would jeopardize the safety
             of the subject or impact the validity of the study results.

          3. Subject has had significant traumatic injury, major surgery or open biopsy within 30
             days prior to study screening.

          4. Subjects with active major depression or a past suicide attempt documented on the
             Baseline/Screening C-SSRS. The children C-SSRS should be used for subjects age 6 to
             11. The adult C-SSRS should be used for subjects 12 and greater years of age.

          5. Any Suicidal Ideation of 3, 4, or 5 or any Suicidal Behavior in Lifetime using C-SSRS.

          6. A history of allergic or adverse responses to diazepam or any comparable or similar
             product.

          7. Subjects who (for whatever reason) have been on an abnormal diet (such as one that
             severely restricts specific basic food groups [e.g., ketogenic diet], limits calories
             [e.g., fast], and/or requires the use of daily supplements as a substitute for the
             foods typically eaten at mealtimes), during the four (4) weeks preceding the study.

          8. Subjects who donated blood or plasma within 30 days of the first dose of study drug.

          9. Participation in a clinical trial within 30 days prior to the first dose of study
             drug. Participation in an observational (non-interventional) study is not excluded as
             long as there are no scheduling conflicts with this study.

         10. Inadequate or difficult venous access that may jeopardize the quality or timing of the
             PK samples.

         11. Female subjects who are trying to conceive, are pregnant, or are lactating.

         12. Positive serum pregnancy test (ß-hCG) at screening or urine pregnancy test prior to
             each administration of study drug for all women of childbearing potential.

         13. Positive blood screen on subjects age 12 or greater for human immunodeficiency virus
             (HIV), Hepatitis B surface antigen (HbSAg), or Hepatitis C, or a positive urine screen
             for alcohol, drugs of abuse, or cotinine. When marijuana was used for medical reasons
             in the opinion of the investigator, it is not considered as drug abuse and the patient
             can be enrolled even if the marijuana metabolites in the urine revealed as positive.

         14. Treatment with phenobarbital or primidone within 30 days of the anticipated dosing
             visit (i.e., baseline).

         15. Treatment with warfarin or dabigatran or other blood thinners within 30 days of the
             anticipated dosing visit (i.e., baseline).

         16. Treatment with any diazepam containing products within 14 days of the anticipated
             dosing visit (i.e., baseline).

         17. Use of nasal decongestants or nasal steroids within 7 days prior to the screening
             visit or during the study.

         18. Subject does not have the flu, rhinitis or any other nasal condition that would impact
             absorption of intranasal diazepam.