A study to test the safety and tolerability of Staccato alprazolam in study participants 12 years of age and older with epilepsy
- Conditions
- Treatment of stereotypical prolonged seizureMedDRA version: 20.0Level: LLTClassification code 10076333Term: Prolonged seizureSystem Organ Class: 10029205 - Nervous system disordersTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2021-002637-42-PL
- Lead Sponsor
- CB Biopharma SR
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 300
- Participant must be =12 years of age at the time of signing informed consent (or giving assent, where required)
- Participant must have a study caregiver =18 years of age at the time of signing the informed consent; the study caregiver(s) must be able to recognize and observe the participant
- Participants with an established diagnosis of focal or generalized epilepsy or combined focal and generalized epilepsy with a documented history of stereotypical episodes of prolonged seizures that includes at least 1 of the following:
a) Generalized seizure episodes starting with a flurry of absence seizures or myoclonic seizures with a minimum total duration of 5 minutes
b) Episodes of a focal seizure with a minimum duration of 3 minutes
c) Episodes of a focal seizure or a flurry of myoclonic seizures for at least 90 seconds followed by a generalized/bilateral tonic-clonic seizure with a minimum total duration of 3 minutes
- Prior to the Screening Visit, participant completed a study using Staccato alprazolam
- Male and female participants:
a) A male participant must agree to use contraception during the Treatment Period and for at least 7 days after investigational medicinal product (IMP) administration
b) A female participant is eligible to participate if she is not pregnant, not breastfeeding, and:
i) Not a woman of childbearing potential (WOCBP)
OR
ii) A WOCBP who agrees to follow the contraceptive guidance during the Treatment Period and for at least 30 days after IMP administration
- Participant is capable of giving signed informed consent (or giving assent, where required).
The informed consent form (ICF) or a specific assent form, where required, will be signed and dated by minors
- The participant’s caregiver(s) must be capable of giving signed informed, which includes compliance with the requirements and restrictions listed in the ICF, the protocol, and the individualized participant management plan (iPMP)
Additional inclusion criteria for treatment arms 2 to 5:
Prior to the Screening Visit, the participant completed the Phase 3
efficacy study with Staccato alprazolam (EP0162) at a clinical site
located in the EU, UK, and UA, and experienced an IMP-treated seizure
during the Outpatient Treatment Period.
Are the trial subjects under 18? yes
Number of subjects for this age range: 49
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 236
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15
- Participant has a current history of alcohol or drug use disorder, as
defined in the Diagnostic and Statistical Manual of Mental Disorders 5,
within the previous 1 year
- Participant has a known hypersensitivity to any components of the
investigational medicinal product (IMP) or comparable drugs (and/or an
investigational device) as stated in this protocol or to albuterol (or
similar bronchospasm rescue medication if needed to meet country-
specific requirements)
- Participant has a history of convulsive (generalized tonic-clonic) status epilepticus in the 8 weeks
prior to the Screening Visit
- Participant has a history or presence of known nonepileptic seizures
which cannot be distinguished from qualifying epileptic seizures
- Participant has a clinically significant known airway hypersensitivity
(eg, bronchospasm to known allergens, such as pollen, animals, or food)
and/or acute respiratory signs/symptoms (eg, shortness of breath,
wheezing on lung auscultation)
- Participant has a clinically significant chronic pulmonary disorder other
than mild asthma (eg, chronic obstructive pulmonary disease, restrictive
lung diseases [including idiopathic pulmonary fibrosis]) and/or recent
history or presence of hemoptysis or pneumothorax
- Participant has had a positive antigen test for SARS-CoV-2 and
experienced moderate to severe signs/symptoms of respiratory distress
necessitating hospitalization or outpatient treatment such as ambulatory
oxygen, extensive treatment with inhaler medications, and/or oral
medications for a duration of 4 weeks or more, unless full resolution
occurred at least 6 months prior to Screening
- Participant has experienced a severe upper respiratory tract infection
within 4 weeks or severe bronchitis/pneumonia within 3 months before
the Screening Visit
- Participant has a history or presence of acute narrow-angle glaucoma
- Participant has a condition for which oral alprazolam is contraindicated
(eg, myasthenia gravis, severe respiratory insufficiency, and sleep apnea
syndrome)
- Participant has a history or presence of long QT syndrome, a family
history of sudden death due to long QT syndrome, or unexplained
syncope
- Participant is taking any drug that is a strong CYP3A4 inhibitor,
including azole antifungal agents (ketoconazole and itraconazole) and
nefazodone
- Participant is taking any opioids (eg, fentanyl, oxycodone, morphine)
or sedative hypnotics on a chronic basis
- Participant is taking nonselective beta blockers on a chronic basis
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Evaluation of the long-term safety and tolerability of Staccato alprazolam;Secondary Objective: - Evaluation of the probability of success of repeated treatment with Staccato alprazolam (for seizures occurring within the first 12 months [up to a maximum of 10 treated seizures])<br>- Evaluation of the probability of success of repeated treatment with Staccato alprazolam with no recurrence of seizure(s) up to 2 hours (for seizures occurring within the first 12 months [up to a maximum of 10 treated seizures])<br>- Evaluation of the long-term pulmonary safety of Staccato alprazolam;Primary end point(s): 1. Frequency of treatment-emergent adverse events (TEAEs)<br>2. Frequency of TEAEs leading to withdrawal from study<br>3. Frequency of serious TEAEs;Timepoint(s) of evaluation of this end point: 1&3: From Baseline up to the End of Study Visit (up to 48 months)
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. Treatment success after investigational medicinal product (IMP) administration for seizures occurring within the first 12 months<br>2. Treatment success after IMP administration with no recurrence after 2 hours for seizures occurring within first 12 months<br>3. Frequency of respiratory TEAEs;Timepoint(s) of evaluation of this end point: 1&2: From start of IMP treatment up to 12 months<br>3: From Baseline up to the End of Study Visit (up to 48 months)