Inpatient, Dose-Ranging Study of Staccato Alprazolam in Epilepsy With Predictable Seizure Pattern
- Registration Number
- NCT03478982
- Lead Sponsor
- Engage Therapeutics, Inc.
- Brief 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 156
-
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.
-
Male or female ≥ 18 years of age.
-
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
-
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.
-
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.
-
Subject is able to comply by the requirements of the protocol, particularly the requirements and specific Institution policies during the in-clinic stay.
- History or diagnosis of non-epileptic seizures (e.g. metabolic or pseudo-seizures).
- History of status epilepticus in the 6 months prior to Screening
- 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
- Use of strong CYP 3A4 inhibitors; including azole antifungal agents (e.g., etoconazole, itraconazole), nefazodone, fluvoxamine, cimetidine, HIV protease inhibitors (e.g., ritonavir)
- Has severe chronic cardio-respiratory disease
- History of HIV-positivity.
- Pregnant or breast-feeding.
- Clinically significant renal or hepatic insufficiency (hepatic transaminases >2 times the upper limit of normal (ULN) or creatinine ≥ 1.5 x ULN).
- History of acute narrow angle glaucoma, Parkinson's disease, hydrocephalus, or history of significant head trauma.
- Subjects who use medications to treat airways disease, such as asthma or COPD or have any acute respiratory signs/symptoms (e.g., wheezing).
- 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
- A history within the past 1 year of drug or alcohol dependence or abuse.
- 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).
- Known allergy or hypersensitivity to alprazolam.
- History of glaucoma.
- Subjects who currently have an active major psychiatric disorder where changes in pharmacotherapy are needed or anticipated during the study.
- 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.
- Significant hepatic, renal, gastroenterologic, cardiovascular (including ischemic heart disease and congestive heart failure), endocrine, neurologic or hematologic disease.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Staccato Alprazolam 2.0 mg Staccato Alprazolam single dose for inhalation Placebo Placebos single dose for inhalation Staccato Alprazolam 1.0 mg Staccato Alprazolam single dose for inhalation
- Primary Outcome Measures
Name Time Method Percentage of Participants in Each Treatment Group Achieving Seizure Activity Cessation Within 2 Minutes and no Recurrent Seizure Within 2 Hours 2 hours post-dosing on dosing day 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.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Seizure Episode Severity Assessed by Seizure Episode Severity Scale 6 hours post-dosing on dosing day 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.
Percentage of Participants With Use of Rescue Medication 2 hours post-dosing on dosing day Percentage of participants with use of rescue medication to stop a seizure episode at the discretion of the principal investigator were reported.
Percentage of Participants With Secondary Generalization (Evolution to a Complex Partial Seizure and/or a Generalized Tonic-Clonic Seizure) 24 hours post-dosing on dosing day Percentage of participants who had seizures that evolved to a complex partial seizure and/or a generalized tonic-clonic seizure were reported.
Trial Locations
- Locations (67)
The Alfred
🇦🇺Melbourne, Victoria, Australia
Lewis Katz School of Medicine at Template University
🇺🇸Philadelphia, Pennsylvania, United States
Hoag Hospital
🇺🇸Newport Beach, California, United States
Hawaii Pacific Neuroscience
🇺🇸Honolulu, Hawaii, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Harvard Medical School - Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
St. Joseph's Hospital and Medical Center - Barrow Neurological Institute
🇺🇸Phoenix, Arizona, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
Oregon Health & Science University - Brain Institute - Comprehensive Epilepsy Center
🇺🇸Portland, Oregon, United States
University of Utah Hospital
🇺🇸Salt Lake City, Utah, United States
UAB Hospital
🇺🇸Birmingham, Alabama, United States
University of Arizona
🇺🇸Phoenix, Arizona, United States
Clinical Trials Inc
🇺🇸Little Rock, Arkansas, United States
Rancho Research Institute Inc.
🇺🇸Downey, California, United States
UCLA
🇺🇸Los Angeles, California, United States
Havana Research Institute LLC.
🇺🇸Pasadena, California, United States
Stanford Neuroscience Health Center
🇺🇸Palo Alto, California, United States
NW FL Clinical Research Group LLC
🇺🇸Gulf Breeze, Florida, United States
Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
GW Medical Faculty Associates
🇺🇸Washington, District of Columbia, United States
VA Connecticut Healthcare System
🇺🇸West Haven, Connecticut, United States
University of Florida Health Science Center Jacksonville
🇺🇸Jacksonville, Florida, United States
Mayo Clinic Florida
🇺🇸Jacksonville, Florida, United States
Clinical Translational Research Site
🇺🇸Miami, Florida, United States
Advanced Pharma Cr, LLC
🇺🇸Miami, Florida, United States
NeuroMedical Research Institute
🇺🇸Panama City, Florida, United States
Nicklaus Children's Hospital
🇺🇸Miami, Florida, United States
Center for Rare Neurological Diseases
🇺🇸Norcross, Georgia, United States
Clinical Research Institute
🇺🇸Stockbridge, Georgia, United States
Ochsner Health System
🇺🇸New Orleans, Louisiana, United States
Maine Medical Center
🇺🇸Scarborough, Maine, United States
SRI International
🇺🇸West Bloomfield, Michigan, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
Impact Clinical Trials Las Vegas
🇺🇸Las Vegas, Nevada, United States
JFK Medical Center
🇺🇸Edison, New Jersey, United States
Institute of Neurology & Neurosurgery at St. Barnabas
🇺🇸Livingston, New Jersey, United States
Dent Neurologic Institute
🇺🇸Amherst, New York, United States
Kaleida Health Oishei Children's Hospital
🇺🇸Buffalo, New York, United States
SUNY Downstate Medical Center - Comprehensive Epilepsy Center
🇺🇸Brooklyn, New York, United States
NYU Comprehensive Epilepsy Center
🇺🇸New York, New York, United States
Mount Sinai Health System
🇺🇸New York, New York, United States
Carolinas Neurosciences Institute
🇺🇸Charlotte, North Carolina, United States
Lenox Hill Hospital
🇺🇸New York, New York, United States
OnSite Clinical Solutions, LLC
🇺🇸Concord, North Carolina, United States
The Promedica-University of Toledo Neuroscience Center
🇺🇸Toledo, Ohio, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
UT Houston
🇺🇸Houston, Texas, United States
University of Texas Southwestern Medical Center - Neurology Clinic
🇺🇸Dallas, Texas, United States
Clinical Trial Network
🇺🇸Houston, Texas, United States
Centra Medical Group Neurology Center
🇺🇸Lynchburg, Virginia, United States
Carilion Roanoke Memorial Hospital
🇺🇸Roanoke, Virginia, United States
Multi-Care Institute for Research and Innovation
🇺🇸Tacoma, Washington, United States
Austin Hospital
🇦🇺Heidelberg, Victoria, Australia
The Tower
🇯🇲Kingston 5, Jamaica
The Royal Melbourne Hospital
🇦🇺Melbourne, Victoria, Australia
Rutgers University
🇺🇸New Brunswick, New Jersey, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
Yale University
🇺🇸New Haven, Connecticut, United States
AdventHealth Orlando
🇺🇸Orlando, Florida, United States
Research Institute of Orlando, LLC
🇺🇸Orlando, Florida, United States
Mid-Atlantic Epilepsy And Sleep Center, LLC
🇺🇸Bethesda, Maryland, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States