A Study to Test the Efficacy and Safety of Staccato Alprazolam in Study Participants 12 Years of Age and Older With Stereotypical Prolonged Seizures

Study Purpose

The purpose of the study is to assess the success of a single administration of Staccato alprazolam compared with placebo both in rapidly terminating a seizure episode within 90 seconds and with no recurrence of seizure(s) up to 2 hours after investigational medicinal product (IMP) administration.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	12 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

- Participant must be ≥12 years of age at the Baseline/Randomization Visit.

- Participant must have a study caregiver ≥18 years of age at the Screening Visit; the study caregiver(s) must be a relative, partner, friend, or legally authorized representative (LAR) of the participant, or a person who provides daily care to the participant and has a significant personal relationship with the participant; the study caregiver(s) must be able to recognize and observe the participant's seizures.

- 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: 1.

Generalized seizure episodes starting with a flurry of absence seizures or myoclonic seizures with a minimum total duration of 5 minutes. 2. Episodes of a focal seizure with a minimum duration of 3 minutes. 3. 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 has experienced ≥4 stereotypical episodes of prolonged seizures in the past 6 months, and the last 2 stereotypical episodes of prolonged seizures must have occurred within the 3 months prior to the Screening Visit.

- Participant has had a documented brain computerized tomography or magnetic resonance imaging review, performed after diagnosis of epilepsy and within the 5 years prior to the Screening Visit, that confirms the absence of a progressive neurological disorder.

- Participant is receiving a regimen of antiseizure medications (ASMs) that has been stable (ie, no addition or removal of ASM[s]; dose adjustments are permitted to ASM[s]; dose adjustments are not permitted for benzodiazepines) for 30 days prior to the Screening Visit.

- Male and female participants: 1.

A male participant must agree to use contraception during the Outpatient Treatment Period and for at least 7 days after IMP administration and refrain from donating sperm during this period. 2. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: i) Not a woman of childbearing potential (WOCBP) OR ii) A WOCBP who agrees to follow the contraceptive guidance during the Outpatient Treatment Period and for at least 30 days after IMP administration.

- Participant is capable of giving signed informed consent (or giving assent, where required), which includes compliance with the requirements and restrictions listed in the informed consent form (ICF), the protocol, and the individualized participant management plan (iPMP).

The ICF or a specific assent form, where required, will be signed and dated by minors.

- The participant's study caregiver(s) must be capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF, the protocol, and the iPMP.

Exclusion Criteria:

- 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 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 diagnosis of atrial fibrillation or mitral stenosis.

- 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 acute respiratory syndrome coronavirus 2 (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 upper respiratory tract infection within 4 weeks or 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.

- Chronic use of benzodiazepines for more than 3 days within a period of 7 days will be allowed for approximately 30 % of study participants.

- 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.

- Participant is taking pharmacotherapy for an active major psychiatric disorder where major changes in regimen are needed or anticipated during the study.

- Participant has been treated with vagal nerve stimulation (VNS) for less than 6 months or VNS settings have changed within 30 days before the Screening Visit.

- Participant has a clinically significant laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results, according to the judgment of the Investigator.

- Participant has an oxygen saturation <95 % (or less than normal in regions of altitude >2500 meters) for greater than 30 seconds during the Screening Visit.

In case of an out-of-range result, 1 repeat will be allowed. If the readings are out of range again, the study participant will be excluded.

- Participant has >2.0x upper limit of normal (ULN) of any of the following: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or >1.0xULN total bilirubin (≥1.5xULN total bilirubin if known Gilbert's syndrome or >2.0xULN total bilirubin for liver impairment) - Participant has current unstable liver or biliary disease per Investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.

- Participant has a QT interval corrected for heart rate (QTc) >450 msec (males), QTc interval >470 msec (females), or QTc interval >480 msec (participants with bundle branch block), PR interval ≥220 msec, or any other clinically significant electrocardiogram (ECG) abnormality according to the Investigator i) The QTc is the QT interval corrected for heart rate according to Fridericia's formula (QTcF).

It is either machine-read or manually over-read.

- Participant has a positive urine screen for drugs of abuse at the Screening Visit.

- Participant has a blood pressure (BP) or heart rate (HR) outside the following range after 5 minutes rest: systolic BP: 90 mmHg to 150 mmHg; diastolic BP: 4 0mmHg to 95 mmHg; HR: 50 bpm to 100 bpm.

In case of an out-of-range result, 1 repeat will be allowed. If the readings are out of range again, the study participant will be excluded

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05077904
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 3
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	UCB Biopharma SRL
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	UCB Cares
Principal Investigator Affiliation	001 844 599 2273 (UCB)
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	Australia, Bulgaria, China, Czechia, France, Germany, Hungary, Italy, Japan, Poland, Spain, United Kingdom, United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Stereotypical Prolonged Seizures

Arms & Interventions

Arms

Experimental: Staccato alprazolam Arm

Participants randomized to this arm will receive a single dose of Staccato alprazolam by inhalation.

Placebo Comparator: Placebo Arm

Participants randomized to this arm will receive a single dose of placebo by inhalation.

Interventions

Drug: - Staccato alprazolam

Route of administration: Inhalation Participants will receive one dose of Staccato alprazolam during the Treatment Period.

Other: - Placebo

Route of administration: Inhalation Participants will receive one dose of placebo during the Treatment Period.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Ep0162 50506, Phoenix 5308655, Arizona 5551752

Status

Recruiting

Address

Ep0162 50506

Phoenix 5308655, Arizona 5551752, 85004

Site Contact

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