Principal Investigator: Angela Peters
Keywords: Alprazolam , Epilepsy , Seizure , rescue medication , abortive medication , Neurology , Intractable seizures Department: Neurology
IRB Number: 00116094 Co Investigator: Amir Arain
Specialty: Neurology, Neurology, Neurology
Sub Specialties: EEG, Long Term Monitoring, Epilepsy
Recruitment Status: Active, not recruiting

Contact Information

Lilly Fagatele

Brief Summary

The overall objectives of the study are to assess the efficacy and safety of a single administration of STAP-001 in subjects with epilepsy with a predictable seizure pattern.

The primary objectives are:

  • To assess the efficacy of STAP-001 (0.5mg and 1.0 mg) compared to placebo in treating a seizure episode
  • To assess the clinical feasibility and safety of the inhalation of STAP-001 (0.5 mg and 1.0 mg) compared to placebo in subjects during a seizure episode
  • To assess the sedation associated with administration of STAP-001 (0.5 mg and 1.0 mg) compared to placebo

Detailed Description

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 as outlined in inclusion criterion #3. 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. A treatable seizure event includes a predictable seizure episode, such that a change in the persistence of the seizure episode can be detected. 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).The study consists of two parts: Part 1 Open-Label Feasibility; Part 2 - Double-Blind. Each part is divided into four phases: Screening; Qualification prior to entering the in-patient unit; Treatment in the in-patient unit; and Post-Treatment Safety Follow-Up. Subjects will provide appropriately-obtained informed consent or will have a legally authorized representative (LAR) sign the informed consent on his or her behalf prior to completing any study-related procedures.The Screening Visit will involve the items identified in the Schedule of Events, including Informed Consent and distribution of the seizure diary. As part of the screening process the seizure events of the subjects must be confirmed as acceptable for continuation in the study by the Epilepsy Study Consortium Review Board. Eligible subjects will enter a Qualification phase during which the subject must have at least 4 or more predictable seizure episodes in a 28-day Qualification Period with no more than one week without a predictable episode. The Qualification Period may be extended beyond 28 days up to 56 total days to provide flexibility for scheduling of the Qualification Visit and Treatment Visit. The 28 days of the seizure diary activity immediately prior to the Qualification Visit will be assessed for qualification. At the end of the Qualification Period the Medical Monitor will review the seizure diary to confirm acceptable seizure frequency and subject’s advancement into the Treatment Phase. Subjects meeting the qualification criteria will enter the CRU/EMU within 7 days from the end of the Qualification Period.Part 1 Open-Label FeasibilityThe first subjects enrolled in the study will participate in an open-label feasibility evaluation. Enrollment in this phase will end when there are data from at least eight individual subjects with a treated single seizure episode in a CRU/EMU. The subjects will be enrolled in 3-8 sites, up to three subjects per site. Eligible and qualified subjects will receive a single dose of 1 mg STAP-001 at the onset of their predictable seizure episode. The subjects will undergo all study procedures and evaluations as outlined in this protocol. The feasibility data (with special emphasis on the drug administration and clinical assessment procedures) from these eight subjects will be analyzed and reviewed by the Sponsor and study team before starting the double-blind part of the study. If deemed necessary based on the feasibility data, the study protocol will be amended (for example, to change the drug administration procedure or to redefine the time frame for primary endpoint assessment), before starting the double-blind part of the study.Part 2: Double-BlindAfter admission to the in-patient unit, eligible and qualified subjects will be randomly assigned (1:1:1) to one of two doses of STAP-001 (1 mg or 2 mg) or Staccato placebo. Randomization will be stratified by the use of inducing vs non-inducing AEDs. For each subject, a single seizure episode will be treated and assessed. Study medication will be self-administered (when feasible) or administered by a Staff Caregiver when a predictable seizure episode starts. Assessment of the seizure activity is based on clinical observation by the Staff Caregiver using a stopwatch. In addition, a video EEG will record the occurrence, start time, and duration of the seizure event. Pharmacokinetic (PK) samples will be collected 10, 30 and 60 minutes, and 2 and 6 hours after the administration of the study drug. If possible, subjects will signal when they experience a seizure event. Subject will be under video EEG surveillance throughout the Treatment Phase. The Staff Caregiver will signal the event for the video EEG recording, start the stop watch at the time of drug administration, and mark the occurrence of the seizure event on a seizure diary. If the seizure episode does not stop within 5 minutes of the study drug administration, rescue medication other than alprazolam may be administered at the discretion of the principal investigator per the protocol of the research unit. The study exit procedures will be conducted 24 to 32 hours after the administration of study medication or when the subject discontinues from the study.After discharge from the in-patient unit there will be a safety-follow-up phone contact 14 days (±2 days) after the subject received the study medication.

Inclusion Criteria

  1. Subject is able to provide written, personally signed, and dated informed consent to participate in the study or will have a legally authorized representative (LAR) 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:
    1. Generalized seizure episodes starting with a flurry of absence seizures or myoclonic seizures with a minimum duration of 5 minutes=
    2. Episodes of a prolonged focal seizure with a minimum duration of 3 minutes
    3. 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-patient 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.