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

• ClinicalTrials.gov Identifier: NCT03478982
• Recruitment Status: Active, not recruiting
• First Posted: March 27, 2018
• Last Update Posted: November 26, 2019
• Sponsor: EngageTherapeutics, Inc.
• Information provided by (Responsible Party): EngageTherapeutics, Inc.

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Epilepsy	Drug: Staccato Alprazolam; Drug: Placebos	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 123 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: March 16, 2018
• Estimated Primary Completion Date: December 2019
• Estimated Study Completion Date: December 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Staccato Alprazolam 1.0 mg; single dose for inhalation	Drug: Staccato Alprazolam; single dose for inhalation; Other Name: STAP-001
Experimental: Staccato Alprazolam 2.0 mg; single dose for inhalation	Drug: Staccato Alprazolam; single dose for inhalation; Other Name: STAP-001
Placebo Comparator: Placebo; single dose for inhalation	Drug: Placebos; single dose for inhalation

Outcome Measures

Primary Outcome Measures :

1. Cessation of seizure activity [ Time Frame: 2 hours post-dosing ]
   EEG activity recorded from the onset of a predictable seizure through two minutes post dosing with study drug and no recurrence of seizure activity within 2 hours

Secondary Outcome Measures :

1. Seizure episode severity [ Time Frame: 6 hours post dosing ]
   Severity of on study episode compared on previously experienced seizures on a 5-point scale (much worse than to much better than)
2. Use of rescue medication [ Time Frame: 5 minutes post-dosing through 2 hours post-dosing ]
   Use of medication to stop a seizure that doesn't respond to study drug 5 minutes post-dose and for up to 2 hours post-dose

Other Outcome Measures:

1. Incidence of treatment emergent adverse events (safety and tolerability) [ Time Frame: Duration of study- From Screening (signing informed consent form) to End-of-Study ~ 6 weeks ] ]
   Incidence of adverse events

Eligibility Criteria

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

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.

Contacts and Locations

  Show 67 Study Locations

Sponsors and Collaborators

EngageTherapeutics, Inc.

Investigators

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

More Information

• Responsible Party: EngageTherapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT03478982 History of Changes
• Other Study ID Numbers: ENGAGE-E-001
• First Posted: March 27, 2018
• Last Update Posted: November 26, 2019
• Last Verified: November 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Epilepsy; Seizures; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Alprazolam; Hypnotics and Sedatives; Central Nervous System Depressants; Physiological Effects of Drugs; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; GABA Modulators; GABA Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action