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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03478982




Registration number
NCT03478982
Ethics application status
Date submitted
7/03/2018
Date registered
27/03/2018
Date last updated
3/02/2021

Titles & IDs
Public title
Inpatient, Dose-Ranging Study of Staccato Alprazolam in Epilepsy With Predictable Seizure Pattern
Scientific 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
Secondary ID [1] 0 0
ENGAGE-E-001
Universal Trial Number (UTN)
Trial acronym
StATES
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Epilepsy 0 0
Condition category
Condition code
Neurological 0 0 0 0
Epilepsy
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Staccato Alprazolam
Treatment: Drugs - Placebos

Experimental: Staccato Alprazolam 1.0 mg - single dose for inhalation

Experimental: Staccato Alprazolam 2.0 mg - single dose for inhalation

Placebo Comparator: Placebo - single dose for inhalation


Treatment: Drugs: Staccato Alprazolam
single dose for inhalation

Treatment: Drugs: Placebos
single dose for inhalation
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants in Each Treatment Group Achieving Seizure Activity Cessation Within 2 Minutes and no Recurrent Seizure Within 2 Hours
Timepoint [1] 0 0
2 hours post-dosing on dosing day
Secondary outcome [1] 0 0
Percentage of Participants With Seizure Episode Severity Assessed by Seizure Episode Severity Scale
Timepoint [1] 0 0
6 hours post-dosing on dosing day
Secondary outcome [2] 0 0
Percentage of Participants With Use of Rescue Medication
Timepoint [2] 0 0
2 hours post-dosing on dosing day
Secondary outcome [3] 0 0
Percentage of Participants With Secondary Generalization (Evolution to a Complex Partial Seizure and/or a Generalized Tonic-Clonic Seizure)
Timepoint [3] 0 0
24 hours post-dosing on dosing day

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
16/03/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
4/01/2020
Sample size
Target
Accrual to date
Final
156
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [2] 0 0
The Alfred - Melbourne
Recruitment hospital [3] 0 0
The Royal Melbourne Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
3084 - Heidelberg
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment postcode(s) [3] 0 0
3050 - Melbourne
Recruitment outside Australia
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United States of America
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Alabama
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United States of America
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Arizona
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United States of America
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Arkansas
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United States of America
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California
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Colorado
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Connecticut
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United States of America
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District of Columbia
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United States of America
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Florida
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Georgia
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Hawaii
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Illinois
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Kansas
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Louisiana
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Maine
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Maryland
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Massachusetts
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Michigan
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Missouri
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Nevada
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New Jersey
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New York
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North Carolina
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Ohio
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Oregon
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Pennsylvania
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Texas
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Utah
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Virginia
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United States of America
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Washington
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Jamaica
State/province [30] 0 0
Kingston 5

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Engage Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/ct2/show/NCT03478982
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
J. Isojarvi, MD, PhD
Address 0 0
Engage Therapeutics, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03478982