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

NCT ID: NCT03478982

Last Updated: 2021-02-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 156 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-16
• Study Completion Date: 2020-01-04

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).

Conditions

Epilepsy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Staccato Alprazolam 1.0 mg

single dose for inhalation

Group Type: EXPERIMENTAL

Staccato Alprazolam

Intervention Type: DRUG

single dose for inhalation

Staccato Alprazolam 2.0 mg

single dose for inhalation

Group Type: EXPERIMENTAL

Staccato Alprazolam

Intervention Type: DRUG

single dose for inhalation

Placebo

single dose for inhalation

Group Type: PLACEBO_COMPARATOR

Placebos

Intervention Type: DRUG

single dose for inhalation

Interventions

Staccato Alprazolam

single dose for inhalation

Intervention Type: DRUG

Placebos

single dose for inhalation

Intervention Type: DRUG

Other Intervention Names

STAP-001

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Engage Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

J. Isojarvi, MD, PhD

Role: STUDY_CHAIR

Engage Therapeutics, Inc.

Locations

UAB Hospital

Birmingham, Alabama, United States

University of Arizona

Phoenix, Arizona, United States

St. Joseph's Hospital and Medical Center - Barrow Neurological Institute

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

Hoag Hospital

Newport Beach, California, United States

Stanford Neuroscience Health Center

Palo Alto, California, United States

Havana Research Institute LLC.

Pasadena, California, United States

University of Colorado

Aurora, Colorado, United States

Yale University

New Haven, Connecticut, United States

VA Connecticut Healthcare System

West Haven, Connecticut, United States

Georgetown University Hospital

Washington D.C., District of Columbia, United States

GW Medical Faculty Associates

Washington D.C., District of Columbia, United States

NW FL Clinical Research Group LLC

Gulf Breeze, Florida, 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

Nicklaus Children's Hospital

Miami, Florida, United States

AdventHealth Orlando

Orlando, Florida, United States

Research Institute of Orlando, LLC

Orlando, Florida, United States

NeuroMedical Research Institute

Panama City, Florida, United States

Center for Rare Neurological Diseases

Norcross, Georgia, United States

Clinical Research Institute

Stockbridge, Georgia, United States

Hawaii Pacific Neuroscience

Honolulu, Hawaii, United States

Northwestern Memorial Hospital

Chicago, Illinois, United States

Rush University Medical Center

Chicago, Illinois, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Ochsner Health System

New Orleans, Louisiana, United States

Maine Medical Center

Scarborough, Maine, United States

Mid-Atlantic Epilepsy And Sleep Center, LLC

Bethesda, Maryland, United States

Harvard Medical School - Brigham and Women's Hospital

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Bronson Methodist Hospital

Kalamazoo, Michigan, United States

SRI International

West Bloomfield, Michigan, United States

Washington University School of Medicine

St Louis, Missouri, 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

Rutgers University

New Brunswick, New Jersey, United States

Dent Neurologic Institute

Amherst, New York, 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

NYU Comprehensive Epilepsy Center

New York, New York, United States

Mount Sinai Health System

New York, New York, United States

Lenox Hill Hospital

New York, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

Carolinas Neurosciences Institute

Charlotte, North Carolina, United States

OnSite Clinical Solutions, LLC

Concord, North Carolina, United States

The Promedica-University of Toledo Neuroscience Center

Toledo, Ohio, United States

Oregon Health & Science University - Brain Institute - Comprehensive Epilepsy Center

Portland, Oregon, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Lewis Katz School of Medicine at Template University

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

University of Texas Southwestern Medical Center - Neurology Clinic

Dallas, Texas, United States

UT Houston

Houston, Texas, United States

Clinical Trial Network

Houston, Texas, United States

University of Utah Hospital

Salt Lake City, Utah, 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 Alfred

Melbourne, Victoria, Australia

The Royal Melbourne Hospital

Melbourne, Victoria, Australia

The Tower

Kingston, , Jamaica

Countries

United States; Australia; Jamaica

References

French J, Biton V, Dave H, Detyniecki K, Gelfand MA, Gong H, Liow K, O'Brien TJ, Sadek A, DiVentura B, Reich B, Isojarvi J. A randomized phase 2b efficacy study in patients with seizure episodes with a predictable pattern using Staccato(R) alprazolam for rapid seizure termination. Epilepsia. 2023 Feb;64(2):374-385. doi: 10.1111/epi.17441. Epub 2022 Dec 7.

Reference Type: DERIVED

PMID: 36268811 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ENGAGE-E-001

Identifier Type: -

Identifier Source: org_study_id