Staccato Alprazolam and Photoparoxysmal Response

NCT02351115 | Completed Phase 2 Results FDA Drug

• 1 other identifier: AMDC-002-202
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to determine whether people who usually have photosensitive epilepsy will show a reduction in epileptic activity when they take a single dose of Staccato Alprazolam as compared to placebo.

Conditions

Epilepsy

Outcome Measures

Primary Outcomes (1)

• Maximum Observed Change From Pretreatment Baseline in the Standardized Photosensitivity Range (SPR)

  Photosensitivity describes the presentation of an epileptiform EEG response (photoparoxysmal response) from exposure to intermittent photic stimulation (IPS). SPR is the number of frequency steps (2, 5, 8, 10, 13, 15, 18, 20, 23, 25, 30, 40, 50 and 60 Hz). between the upper and lower limits of sensitivity to IPS for that patient at that time, in order not to evoke seizures. Thus a reduction (-change) means the intervention is working (desired effect on sensitivity)

  SPR was recorded pretreatment, 2, 10, 30 min, 1, 2, 4, and 6 hr post each study drug administration The maximum change from baseline occurred at: 10 min for alprazolam 2 mg, 1 hour for alprazolam 0.5 and 1 mg and placebo

Secondary Outcomes (5)

• Maximum Sedation Using Visual Analog Scale (Sedated-Alert)

  Sedation was recorded pretreatment, 2, 10, 30 min, 1, 2, 4, and 6 hr post each study drug administration The maximum change from baseline occurred at:: 30 min for alprazolam 1 mg, 1 hour for alprazolam 0.5 and 2 mg, and 4 hours for placebo

• Maximum Sedation Using Visual Analog Scale (Sleepy-Awake)

  Sleepiness was recorded pretreatment, 2, 10, 30 min, 1, 2, 4, and 6 hr post each study drug administration The maximum change from baseline occurred: at: 30 min for alprazolam 1 mg, 1 hour for alprazolam 0.5 and 2 mg and placebo

• Correlation of Plasma Concentrations of Alprazolam With Pharmacodynamic Effects on Standardized Photosensitivity Range (SPR)

  Pretreatment, 2, 10, 30 min, 1, 2, 4, and 6 hr post each study drug administration

• Correlation of Plasma Concentrations of Alprazolam With Pharmacodynamic Effects on Visual Analog Scale (Sedated-Alert)

  Pretreatment, 2, 10, 30 min, 1, 2, 4, and 6 hr post each study drug administration

• Correlation of Plasma Concentrations of Alprazolam With Pharmacodynamic Effects on Visual Analog Scale (Sleepy-Awake)

  Pretreatment, 2, 10, 30 min, 1, 2, 4, and 6 hr post each study drug administration

Study Arms (5)

Sequence BEADC

EXPERIMENTAL

A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo

Drug: A=Placebo; Drug: B=Inhaled Alprazolam 0.5 mg; Drug: C=Inhaled Alprazolam 1 m; Drug: D= Inhaled Alprazolam 2 mg; Drug: E=Placebo

Sequence CDAEB

EXPERIMENTAL

A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo

Drug: A=Placebo; Drug: B=Inhaled Alprazolam 0.5 mg; Drug: C=Inhaled Alprazolam 1 m; Drug: D= Inhaled Alprazolam 2 mg; Drug: E=Placebo

Sequence DEBAC

EXPERIMENTAL

A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo

Drug: A=Placebo; Drug: B=Inhaled Alprazolam 0.5 mg; Drug: C=Inhaled Alprazolam 1 m; Drug: D= Inhaled Alprazolam 2 mg; Drug: E=Placebo

Sequence EDBAC

EXPERIMENTAL

A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo

Drug: A=Placebo; Drug: B=Inhaled Alprazolam 0.5 mg; Drug: C=Inhaled Alprazolam 1 m; Drug: D= Inhaled Alprazolam 2 mg; Drug: E=Placebo

Sequence CABED

EXPERIMENTAL

A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo

Drug: A=Placebo; Drug: B=Inhaled Alprazolam 0.5 mg; Drug: C=Inhaled Alprazolam 1 m; Drug: D= Inhaled Alprazolam 2 mg; Drug: E=Placebo

Interventions

A=Placebo DRUG

Sequence BEADC; Sequence CABED; Sequence CDAEB; Sequence DEBAC; Sequence EDBAC

E=Placebo DRUG

Sequence BEADC; Sequence CABED; Sequence CDAEB; Sequence DEBAC; Sequence EDBAC

B=Inhaled Alprazolam 0.5 mg DRUG

Sequence BEADC; Sequence CABED; Sequence CDAEB; Sequence DEBAC; Sequence EDBAC

C=Inhaled Alprazolam 1 m DRUG

Sequence BEADC; Sequence CABED; Sequence CDAEB; Sequence DEBAC; Sequence EDBAC

D= Inhaled Alprazolam 2 mg DRUG

Sequence BEADC; Sequence CABED; Sequence CDAEB; Sequence DEBAC; Sequence EDBAC

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female subjects between the ages of 18 to 60 years, inclusive
• Body mass index (BMI) ≥18 and ≤35 kg/m2
• Able to speak, read, and understand English and willing and able to provide written informed consent on an IRB-approved form before the initiation of any study procedures
• A diagnosis and history of a photoparoxysmal response on EEG with or without a diagnosis of epilepsy for which patients are on 0-2 concomitant antiepileptic drugs
• At least 3 of the EEGs performed during the screen visit must have a reproducible IPS-induced photoparoxysmal response (PPR) on EEG of at least 3 points on a frequency assessment scale in at least one eye condition
• In otherwise good general health as determined by a complete medical history, physical examination, 12-lead ECG, blood chemistry profile, hematology, and urinalysis
• 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

You may not qualify if:

• History of non-epileptic seizures (e.g. metabolic, structural, or pseudo-seizures)
• History of seizure worsening in response to narrow spectrum drugs
• An active CNS infection, demyelinating disease, degenerative neurological disease or any CNS disease deemed to be progressive during the course of the study that may confound the interpretation of the study results
• Use of more than 2 concomitant AEDs for epilepsy treatment
• Subjects taking known inhibitors or inducers of CYP3A , including carbamazepine
• Subjects with a history of allergic reactions to alprazolam or other benzodiazepines
• Treatment with an investigational drug within 30 days (or within 5 half-lives of the investigational drug, if \>30 days) before Visit 2
• A history within the past 1 year of drug or alcohol dependence or abuse
• Positive urine screen for drugs of abuse at Visit 1 - Screening
• A history of HIV-positivity
• Female subjects who have a positive pregnancy test at screening or prior to test sessions or are breastfeeding
• History of acute narrow angle glaucoma, Parkinson's disease, hydrocephalus, or history of significant head trauma
• Subjects who have a current history of asthma, chronic obstructive lung disease (COPD), or any lung disease associated with bronchospasm
• Subjects who use medications to treat airways disease, such as asthma or COPD
• Subjects who have any acute respiratory signs/symptoms (e.g., wheezing)

Sponsors & Collaborators

• The Epilepsy Study Consortium: collaborator
• Nova Pneuma Inc.: lead

Study Sites (3)

Consultants in Epilepsy & Neurology, PLLC

Boise, Idaho, United States

Location

New York University Epilepsy Center

New York, New York, United States

Location

University of Pennsylvania - Penn Epilepsy Center

Philadelphia, Pennsylvania, United States

Location

MeSH Terms

Conditions

Epilepsy

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Engage Therapeutics, Inc

studydirector@engagetherapeutics.com

Study Officials

• J Isojarvi, MD

  Engage Therapeutics, Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2015
• First Posted: January 30, 2015
• Study Start: January 1, 2015
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: April 20, 2026
• Results First Posted: August 10, 2021

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Within 10 days of request approval
• Access Criteria: Approval of formal request for access

Locations

US (3)