Inpatient, Dose-Ranging Study of Staccato Alprazolam in Epilepsy With Predictable Seizure Pattern
Inpatient, Dose-Ranging Study of Staccato Alprazolam in Epilepsy With Predictable Seizure Pattern
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).
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.