Clinical trial NCT03478982: Inpatient, Dose-Ranging Study of Staccato Alprazolam in Epilepsy With Predictable Seizure Pattern
Official title: A Double-Blind, Placebo-Controlled, Inpatient, Dose-Ranging Efficacy Study of Staccato Alprazolam (STAP-001) in Subjects With Epilepsy With a Predictable Seizure Pattern
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Epilepsy
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2018-03-27
Enrollment: 156
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Percentage of Participants in Each Treatment Group Achieving Seizure Activity Cessation Within 2 Minutes and no Recurrent Seizure Within 2 Hours
timeFrame: 2 hours post-dosing on dosing day
Secondary outcomes:
measure: Percentage of Participants With Seizure Episode Severity Assessed by Seizure Episode Severity Scale
timeFrame: 6 hours post-dosing on dosing day
measure: Percentage of Participants With Use of Rescue Medication
timeFrame: 2 hours post-dosing on dosing day
measure: Percentage of Participants With Secondary Generalization (Evolution to a Complex Partial Seizure and/or a Generalized Tonic-Clonic Seizure)
timeFrame: 24 hours post-dosing on dosing day
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Hospital
state: Alabama
city: Phoenix
country: United States
facility: University of Arizona
state: Arizona
city: Phoenix
country: United States
facility: St. Joseph's Hospital and Medical Center - Barrow Neurological Institute
state: Arizona
city: Little Rock
country: United States
facility: Clinical Trials Inc
state: Arkansas
city: Downey
country: United States
facility: Rancho Research Institute Inc.
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Newport Beach
country: United States
facility: Hoag Hospital
state: California
city: Palo Alto
country: United States
facility: Stanford Neuroscience Health Center
state: California
city: Pasadena
country: United States
facility: Havana Research Institute LLC.
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: West Haven
country: United States
facility: VA Connecticut Healthcare System
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Washington
country: United States
facility: GW Medical Faculty Associates
state: District of Columbia
city: Gulf Breeze
country: United States
facility: NW FL Clinical Research Group LLC
state: Florida
city: Jacksonville
country: United States
facility: University of Florida Health Science Center Jacksonville
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Miami
country: United States
facility: Clinical Translational Research Site
state: Florida
city: Miami
country: United States
facility: Advanced Pharma Cr, LLC
state: Florida
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: Orlando
country: United States
facility: Research Institute of Orlando, LLC
state: Florida
city: Panama City
country: United States
facility: NeuroMedical Research Institute
state: Florida
city: Norcross
country: United States
facility: Center for Rare Neurological Diseases
state: Georgia
city: Stockbridge
country: United States
facility: Clinical Research Institute
state: Georgia
city: Honolulu
country: United States
facility: Hawaii Pacific Neuroscience
state: Hawaii
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: New Orleans
country: United States
facility: Ochsner Health System
state: Louisiana
city: Scarborough
country: United States
facility: Maine Medical Center
state: Maine
city: Bethesda
country: United States
facility: Mid-Atlantic Epilepsy And Sleep Center, LLC
state: Maryland
city: Boston
country: United States
facility: Harvard Medical School - Brigham and Women's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: West Bloomfield
country: United States
facility: SRI International
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Las Vegas
country: United States
facility: Impact Clinical Trials Las Vegas
state: Nevada
city: Edison
country: United States
facility: JFK Medical Center
state: New Jersey
city: Livingston
country: United States
facility: Institute of Neurology & Neurosurgery at St. Barnabas
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers University
state: New Jersey
city: Amherst
country: United States
facility: Dent Neurologic Institute
state: New York
city: Brooklyn
country: United States
facility: SUNY Downstate Medical Center - Comprehensive Epilepsy Center
state: New York
city: Buffalo
country: United States
facility: Kaleida Health Oishei Children's Hospital
state: New York
city: New York
country: United States
facility: NYU Comprehensive Epilepsy Center
state: New York
city: New York
country: United States
facility: Mount Sinai Health System
state: New York
city: New York
country: United States
facility: Lenox Hill Hospital
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Charlotte
country: United States
facility: Carolinas Neurosciences Institute
state: North Carolina
city: Concord
country: United States
facility: OnSite Clinical Solutions, LLC
state: North Carolina
city: Toledo
country: United States
facility: The Promedica-University of Toledo Neuroscience Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University - Brain Institute - Comprehensive Epilepsy Center
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Lewis Katz School of Medicine at Template University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center - Neurology Clinic
state: Texas
city: Houston
country: United States
facility: UT Houston
state: Texas
city: Houston
country: United States
facility: Clinical Trial Network
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Hospital
state: Utah
city: Lynchburg
country: United States
facility: Centra Medical Group Neurology Center
state: Virginia
city: Roanoke
country: United States
facility: Carilion Roanoke Memorial Hospital
state: Virginia
city: Tacoma
country: United States
facility: Multi-Care Institute for Research and Innovation
state: Washington
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred
state: Victoria
city: Melbourne
country: Australia
facility: The Royal Melbourne Hospital
state: Victoria
city: Kingston 5
country: Jamaica
facility: The Tower
Study officials:
affiliation: Engage Therapeutics, Inc.
name: J. Isojarvi, MD, PhD
role: STUDY_CHAIR
References: