The StATES trial (Inpatient, Dose-Ranging Study of Staccato Alprazolam in Epilepsy With Predictable Seizure Pattern) is a study to investigate the efficacy, safety and clinical usability of Staccato Alprazolam (STAP-001) in adult subjects (18 years and older) with epilepsy with a predictable seizure pattern.
Adult subjects that have an established diagnosis of focal or generalized epilepsy with a documented history of predictable seizure episodes are eligible for this trial.
This is a multi-center, double-blind, randomized, in-patient study. 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.
What are the possible outcomes of this study?
Once the subject enters the CRU or EMU and has a seizure, they will be treated with STAP-001. One seizure per subject will be treated. STAP-001 is delivered orally to the deep lung for systemic delivery. The Staccato delivery system is user-friendly and easy to use and accomplished with a single, normal breath by the subject.
The duration and timing of the seizure event and occurrence of subsequent seizures will be assessed by the Staff Caregiver(s) through clinical observation and confirmed with video electroencephalogram (EEG).
The following measures will be assessed:
- If the seizure stopped within two minutes of administering STAP-001
- If seizures recurred within 2 to 12 hours after giving STAP-001
- Seizure duration
- Seizure severity
- The use of rescue medication to stop a seizure that doesn’t respond to the study drug 5 minutes post-drug and for up to 2 hours post-drug
Who is eligible to participate in this study?
Subjects may be eligible to participate in this study if they meet certain inclusion criteria, including:
- Subject is able to provide, personally signed and dated informed consent to participate in the study or will have a legally authorized representative (LAR) sign the informed consent on his or her behalf before completing any study related procedures
- Male or female adult (18 years or older)
- Subject has an established diagnosis of focal or 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
- Multiple (?2) focal seizures within a 2-hour time period
- 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 the Screening Visit
- 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
- Subject is able to comply by the requirements of the protocol, particularly the requirements and specific Institution policies during the in-clinic stay
Who is not eligible to participate in the study:
Potential participants will be excluded from the study if they meet the following exclusion criteria:
- History or diagnosis of non-epileptic seizures (e.g. metabolic or pseudo-seizures)
- History of status epilepticus in the 6 months prior to Screening
- 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
- Receiving chronic benzodiazepine treatment (defined as an average of ? 4 administrations per week) prior to admission to the in-patient unit
- Use of strong CYP 3A4 inhibitors; including azole antifungal agents (e.g., etoconazole, itraconazole), nefazodone, fluvoxamine, cimetidine, HIV protease inhibitors (e.g., ritonavir)
- Has severe chronic cardio-respiratory disease
- History of HIV-positivity
- Pregnant or breast-feeding
- Clinically significant renal or hepatic insufficiency (hepatic transaminases >2 times the upper limit of normal (ULN) or creatinine ? 1.5 x ULN)
- History of acute narrow angle glaucoma, Parkinson’s disease, hydrocephalus, or history of significant head trauma
- Subjects who use medications to treat airways disease, such as asthma or COPD or have any acute respiratory signs/symptoms (e.g., wheezing)
- 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
- A history within the past 1 year of drug or alcohol dependence or abuse
- 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)
Are there any risks to participating in this study?
In a prior study of the effects of STAP-001 in individuals with epilepsy, dose-related sedation was the most common adverse event. Overall, STAP-001 was well-tolerated and no serious adverse events were reported. Vital signs, heart rhythm, and brain activity will be monitored throughout the inpatient period of the study to monitor for sedation.
What is required of me?
StATES 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. The total StATES trial will be about 8 to 12 weeks long, including the screening and follow-up periods.
After an initial screening in an outpatient visit, you will be followed for 4 weeks to make sure you are eligible for the study. During this period, you will record your seizure activity in a daily seizure diary. If your seizure pattern qualifies, you will be randomly assigned to either the study drug or a placebo. Neither you nor the study administrator will know which medicine you are getting.
The treatment phase of the study will occur next. You will be admitted to a CRU or EMU in anticipation of a seizure. After you have a seizure, you will be given one dose of STAP-001 or placebo. You will be followed for at least 12 hours after the medicine is given.
Following discharge from the CRU or EMU, your last study visit will be done by a phone call with a study coordinator 12-16 days after you received the study drug (STAP-001).
What is the total time involved?
The StATES study will take a total of 8 to 12 weeks.
What are the study time frames?
Actual study start date: March 16, 2018
Estimated Primary Completion Date: May 2019
Estimated Study Completion Date: May 2019
How do I find out more information about this study?
If you would like to see if you are eligible to participate please visit www.epilepsyhealthstudy.com. You may also contact the program director at: firstname.lastname@example.org.