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

A Double-Blind, Placebo-Controlled, Inpatient, Dose-Ranging Efficacy Study of Staccato Alprazolam (STAP-001) in Subjects With Epilepsy With a 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).

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Drug: Staccato Alprazolam; Drug: Placebos

• Study Type: Interventional
• Enrollment (Actual): 156
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Austin Hospital
    • Melbourne, Victoria, Australia, 3050
      • The Royal Melbourne Hospital
    • Melbourne, Victoria, Australia, 3004
      • The Alfred
• Jamaica
  • Kingston 5, Jamaica
    • The Tower
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • UAB Hospital
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • University of Arizona
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hospital and Medical Center - Barrow Neurological Institute
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Clinical Trials Inc
  • California
    • Downey, California, United States, 90242
      • Rancho Research Institute Inc.
    • Los Angeles, California, United States, 90095
      • UCLA
    • Newport Beach, California, United States, 92663
      • Hoag Hospital
    • Palo Alto, California, United States, 94304
      • Stanford Neuroscience Health Center
    • Pasadena, California, United States, 91105
      • Havana Research Institute LLC.
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University
    • West Haven, Connecticut, United States, 06516
      • VA Connecticut Healthcare System
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Hospital
    • Washington, District of Columbia, United States, 20037
      • GW Medical Faculty Associates
  • Florida
    • Gulf Breeze, Florida, United States, 32561
      • NW FL Clinical Research Group LLC
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Florida
    • Jacksonville, Florida, United States, 32209
      • University of Florida Health Science Center Jacksonville
    • Miami, Florida, United States, 33155
      • Nicklaus Children's Hospital
    • Miami, Florida, United States, 33147
      • Advanced Pharma Cr, LLC
    • Miami, Florida, United States, 33136
      • Clinical Translational Research Site
    • Orlando, Florida, United States, 32803
      • AdventHealth Orlando
    • Orlando, Florida, United States, 32806
      • Research Institute of Orlando, LLC
    • Panama City, Florida, United States, 33607
      • NeuroMedical Research Institute
  • Georgia
    • Norcross, Georgia, United States, 30093
      • Center for Rare Neurological Diseases
    • Stockbridge, Georgia, United States, 30281
      • Clinical Research Institute
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Hawaii Pacific Neuroscience
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Health System
  • Maine
    • Scarborough, Maine, United States, 04074
      • Maine Medical Center
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Mid-Atlantic Epilepsy and Sleep Center, LLC
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Harvard Medical School - Brigham and Women's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • West Bloomfield, Michigan, United States, 48322
      • SRI International
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Impact Clinical Trials Las Vegas
  • New Jersey
    • Edison, New Jersey, United States, 08820
      • JFK Medical Center
    • Livingston, New Jersey, United States, 07039
      • Institute of Neurology & Neurosurgery at St. Barnabas
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers University
  • New York
    • Amherst, New York, United States, 14226
      • Dent Neurologic Institute
    • Brooklyn, New York, United States, 11203
      • SUNY Downstate Medical Center - Comprehensive Epilepsy Center
    • Buffalo, New York, United States, 14203
      • Kaleida Health Oishei Children's Hospital
    • New York, New York, United States, 10029
      • Mount Sinai Health System
    • New York, New York, United States, 10075
      • Lenox Hill Hospital
    • New York, New York, United States, 10016
      • NYU Comprehensive Epilepsy Center
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Carolinas Neurosciences Institute
    • Concord, North Carolina, United States, 28025
      • OnSite Clinical Solutions, LLC
  • Ohio
    • Toledo, Ohio, United States, 43606
      • The Promedica-University of Toledo Neuroscience Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University - Brain Institute - Comprehensive Epilepsy Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Philadelphia, Pennsylvania, United States, 19140
      • Lewis Katz School of Medicine at Template University
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center - Neurology Clinic
    • Houston, Texas, United States, 77074
      • Clinical Trial Network
    • Houston, Texas, United States, 77030
      • UT Houston
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Hospital
  • Virginia
    • Lynchburg, Virginia, United States, 24502
      • Centra Medical Group Neurology Center
    • Roanoke, Virginia, United States, 24014
      • Carilion Roanoke Memorial Hospital
  • Washington
    • Tacoma, Washington, United States, 98405
      • Multi-Care Institute for Research and Innovation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Staccato Alprazolam 1.0 mg; single dose for inhalation	Drug: Staccato Alprazolam; single dose for inhalation; Other Names: STAP-001
Experimental: Staccato Alprazolam 2.0 mg; single dose for inhalation	Drug: Staccato Alprazolam; single dose for inhalation; Other Names: STAP-001
Placebo Comparator: Placebo; single dose for inhalation	Drug: Placebos; single dose for inhalation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants in Each Treatment Group Achieving Seizure Activity Cessation Within 2 Minutes and no Recurrent Seizure Within 2 Hours	Percentage of participants with onset of a predictable seizure through 2 minutes post dosing with study drug and no recurrence of seizure activity within 2 hours were reported for each treatment group based on clinical observation.	2 hours post-dosing on dosing day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Seizure Episode Severity Assessed by Seizure Episode Severity Scale	Severity of on study seizure episode compared to previously experienced seizures was assessed with Seizure Episode Severity Scale. It is a 5-point scale with range from 1 to 5, where 1 indicates much worse than and 5 indicates much better than.	6 hours post-dosing on dosing day
Percentage of Participants With Use of Rescue Medication	Percentage of participants with use of rescue medication to stop a seizure episode at the discretion of the principal investigator were reported.	2 hours post-dosing on dosing day
Percentage of Participants With Secondary Generalization (Evolution to a Complex Partial Seizure and/or a Generalized Tonic-Clonic Seizure)	Percentage of participants who had seizures that evolved to a complex partial seizure and/or a generalized tonic-clonic seizure were reported.	24 hours post-dosing on dosing day

Collaborators and Investigators

• Sponsor: Engage Therapeutics, Inc.
• Investigators: Study Chair: J. Isojarvi, MD, PhD, Engage Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2018
• Primary Completion (Actual): December 22, 2019
• Study Completion (Actual): January 4, 2020

Study Registration Dates

• First Submitted: March 7, 2018
• First Submitted That Met QC Criteria: March 20, 2018
• First Posted (Actual): March 27, 2018

Study Record Updates

• Last Update Posted (Actual): February 3, 2021
• Last Update Submitted That Met QC Criteria: February 2, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Epilepsy; Seizures; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Alprazolam
• Other Study ID Numbers: ENGAGE-E-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a prespecified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.
• IPD Sharing Time Frame: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
• IPD Sharing Access Criteria: Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No