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

Epilepsy Clinical Trial

— StATES  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03478982
• Other study ID #: ENGAGE-E-001
• Status: Completed
• Phase: Phase 2
• Start date: March 16, 2018
• Est. completion date: January 4, 2020

Study information

• Verified date: February 2021
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 156
• Est. completion date: January 4, 2020
• Est. primary completion date: December 22, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Epilepsy
• Seizures

Intervention

Drug:
• Staccato Alprazolam
single dose for inhalation
• Placebos
single dose for inhalation

Locations

Country	Name	City	State
Australia	Austin Hospital	Heidelberg	Victoria
Australia	The Alfred	Melbourne	Victoria
Australia	The Royal Melbourne Hospital	Melbourne	Victoria
Jamaica	The Tower	Kingston 5
United States	Dent Neurologic Institute	Amherst	New York
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Colorado	Aurora	Colorado
United States	Mid-Atlantic Epilepsy And Sleep Center, LLC	Bethesda	Maryland
United States	UAB Hospital	Birmingham	Alabama
United States	Harvard Medical School - Brigham and Women's Hospital	Boston	Massachusetts
United States	SUNY Downstate Medical Center - Comprehensive Epilepsy Center	Brooklyn	New York
United States	Kaleida Health Oishei Children's Hospital	Buffalo	New York
United States	Carolinas Neurosciences Institute	Charlotte	North Carolina
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	OnSite Clinical Solutions, LLC	Concord	North Carolina
United States	University of Texas Southwestern Medical Center - Neurology Clinic	Dallas	Texas
United States	Rancho Research Institute Inc.	Downey	California
United States	JFK Medical Center	Edison	New Jersey
United States	NW FL Clinical Research Group LLC	Gulf Breeze	Florida
United States	Hawaii Pacific Neuroscience	Honolulu	Hawaii
United States	Clinical Trial Network	Houston	Texas
United States	UT Houston	Houston	Texas
United States	Mayo Clinic Florida	Jacksonville	Florida
United States	University of Florida Health Science Center Jacksonville	Jacksonville	Florida
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Impact Clinical Trials Las Vegas	Las Vegas	Nevada
United States	Clinical Trials Inc	Little Rock	Arkansas
United States	Institute of Neurology & Neurosurgery at St. Barnabas	Livingston	New Jersey
United States	UCLA	Los Angeles	California
United States	Centra Medical Group Neurology Center	Lynchburg	Virginia
United States	Advanced Pharma Cr, LLC	Miami	Florida
United States	Clinical Translational Research Site	Miami	Florida
United States	Nicklaus Children's Hospital	Miami	Florida
United States	Rutgers University	New Brunswick	New Jersey
United States	Yale University	New Haven	Connecticut
United States	Ochsner Health System	New Orleans	Louisiana
United States	Lenox Hill Hospital	New York	New York
United States	Mount Sinai Health System	New York	New York
United States	NYU Comprehensive Epilepsy Center	New York	New York
United States	Hoag Hospital	Newport Beach	California
United States	Center for Rare Neurological Diseases	Norcross	Georgia
United States	AdventHealth Orlando	Orlando	Florida
United States	Research Institute of Orlando, LLC	Orlando	Florida
United States	Stanford Neuroscience Health Center	Palo Alto	California
United States	NeuroMedical Research Institute	Panama City	Florida
United States	Havana Research Institute LLC.	Pasadena	California
United States	Lewis Katz School of Medicine at Template University	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	St. Joseph's Hospital and Medical Center - Barrow Neurological Institute	Phoenix	Arizona
United States	University of Arizona	Phoenix	Arizona
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University - Brain Institute - Comprehensive Epilepsy Center	Portland	Oregon
United States	Carilion Roanoke Memorial Hospital	Roanoke	Virginia
United States	University of Rochester Medical Center	Rochester	New York
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of Utah Hospital	Salt Lake City	Utah
United States	Maine Medical Center	Scarborough	Maine
United States	Clinical Research Institute	Stockbridge	Georgia
United States	Multi-Care Institute for Research and Innovation	Tacoma	Washington
United States	The Promedica-University of Toledo Neuroscience Center	Toledo	Ohio
United States	Georgetown University Hospital	Washington	District of Columbia
United States	GW Medical Faculty Associates	Washington	District of Columbia
United States	SRI International	West Bloomfield	Michigan
United States	VA Connecticut Healthcare System	West Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Engage Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Jamaica, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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