Inpatient, Dose-Ranging Study of Staccato Alprazolam in Epilepsy With Predictable Seizure Pattern
Condition: Epilepsy
MeSH terms: Epilepsy; Seizures
Intervention: Staccato Alprazolam; Placebos
Intervention description: single dose for inhalation; single dose for inhalation
Intervention MeSH terms: Alprazolam
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 156.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a multi-center, double-blind, randomized, parallel group, dose-ranging study to
      investigate the efficacy and clinical usability of STAP-001 in adult (18 years of age and
      older) subjects with epilepsy with a predictable seizure pattern. These subjects have an
      established diagnosis of focal or generalized epilepsy with a documented history of
      predictable seizure episodes. This is an in-patient study. The subjects will be admitted to a
      Clinical Research Unit (CRU) or Epilepsy Monitoring Unit (EMU) for study participation. The
      duration of the stay in the in-patient unit will be 2-8 days. One seizure event per subject
      will be treated with study medication. The duration and timing of the seizure event and
      occurrence of subsequent seizures will be assessed by the Staff Caregiver(s)1 through
      clinical observation and confirmed with video electroencephalogram (EEG).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subject is able to provide, personally signed, and dated informed consent to
             participate in the study or will have a legally authorized representative sign the
             informed consent on his or her behalf before completing any study related procedures.

          2. Male or female ≥ 18 years of age.

          3. Has an established diagnosis of focal or generalized epilepsy or focal and generalized
             epilepsy with a documented history of predictable seizure episodes that includes at
             least one of the following:

               -  Generalized seizure episodes starting with a flurry of absence seizures or
                  myoclonic seizures with a minimum duration of 5 minutes

               -  Episodes of a prolonged focal seizure with a minimum duration of 3 minutes

               -  Episodes of multiple (≥2) seizures within a 2-hour time period

          4. Prior to randomization, has experienced ≥4 seizure episodes with predictable pattern
             during the last 4 weeks (qualification period) and no more than one week without a
             predictable seizure episode before entry into the in-patient unit.

          5. Female participants (if of child-bearing potential and sexually active) and male
             participants (if sexually active with a partner of child-bearing potential) who agree
             to use a medically acceptable and effective birth control method throughout the study
             and for 1 week following the end of the study. Medically acceptable methods of
             contraception that may be used by the participant and/or his/her partner include
             abstinence, birth control pills or patches, diaphragm with spermicide,intrauterine
             device (IUD), surgical sterilization, and progestin implant or injection. Prohibited
             methods include: the rhythm method, withdrawal, condoms alone, or diaphragm alone.

          6. Subject is able to comply by the requirements of the protocol, particularly the
             requirements and specific Institution policies during the in-clinic stay.

        Exclusion Criteria:

          1. History or diagnosis of non-epileptic seizures (e.g. metabolic or pseudo-seizures).

          2. History of status epilepticus in the 6 months prior to Screening

          3. Has 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 3 months

          4. Use of strong CYP 3A4 inhibitors; including azole antifungal agents (e.g.,
             etoconazole, itraconazole), nefazodone, fluvoxamine, cimetidine, HIV protease
             inhibitors (e.g., ritonavir)

          5. Has severe chronic cardio-respiratory disease

          6. History of HIV-positivity.

          7. Pregnant or breast-feeding.

          8. Clinically significant renal or hepatic insufficiency (hepatic transaminases >2 times
             the upper limit of normal (ULN) or creatinine ≥ 1.5 x ULN).

          9. History of acute narrow angle glaucoma, Parkinson's disease, hydrocephalus, or history
             of significant head trauma.

         10. Subjects who use medications to treat airways disease, such as asthma or COPD or have
             any acute respiratory signs/symptoms (e.g., wheezing).

         11. Use of any investigational drug within 30 days or 5 half-lives of the investigational
             drug prior to administration of study medication, whichever is longer

         12. A history within the past 1 year of drug or alcohol dependence or abuse.

         13. Positive urine screen for drugs of abuse at Screening.(positive Cannabis/Cannabinol
             results are acceptable if there is a documented history of stable use for medical
             purposes).

         14. Known allergy or hypersensitivity to alprazolam.

         15. History of glaucoma.

         16. Subjects who currently have an active major psychiatric disorder where changes in
             pharmacotherapy are needed or anticipated during the study.

         17. Hypotension (systolic blood pressure ≤90 mm Hg, diastolic blood pressure ≤50 mm Hg),
             or hypertension (systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥100 mm
             Hg) measured while seated at screening or baseline.

         18. Significant hepatic, renal, gastroenterologic, cardiovascular (including ischemic
             heart disease and congestive heart failure), endocrine, neurologic or hematologic
             disease.

         19. Subjects who, in the opinion of the Investigator, should not participate in the study
             for any reason, including if there is a question about the stability or capability of
             the subject to comply with the trial requirements.