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NCT05077904PHASE3Recruiting

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

UCB Biopharma SRL

Start Date

12/7/2021

Completion Date

8/31/2026

Summary

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.

Eligibility Criteria

Age Range: 12 years to No maximum

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

Interventions

DRUG

Staccato alprazolam

OTHER

Placebo

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Conditions

Stereotypical Prolonged Seizures

Locations

Ep0162 50506

Phoenix, Arizona 85004

United States

Ep0162 50720

Scottsdale, Arizona 85253

United States

Ep0162 50494

Little Rock, Arkansas 72205

United States

Ep0162 50118

Downey, California 90242

United States

Ep0162 50416

La Jolla, California 92037

United States

Ep0162 50702

Long Beach, California 90806

United States

Ep0162 50505

Los Angeles, California 90095

United States

Ep0162 50492

Orange, California 92868

United States

Ep0162 50722

Poway, California 92064

United States

Ep0162 50716

Sacramento, California 95817

United States

Ep0162 50367

New Haven, Connecticut 06519

United States

Ep0162 50088

Washington D.C., District of Columbia 20037

United States

Ep0162 50721

Boca Raton, Florida 33486

United States

Ep0162 50515

Gulf Breeze, Florida 32561

United States

Ep0162 50508

Jacksonville, Florida 32209-6533

United States

Ep0162 50342

Jacksonville, Florida 32224-1865

United States

Ep0162 50199

Miami, Florida 33136

United States

Ep0162 50676

Miami, Florida 33176

United States

Ep0162 50509

Orlando, Florida 32806

United States

Ep0162 50703

Rockledge, Florida 32955

United States

Ep0162 50308

Tampa, Florida 33606

United States

Ep0162 50323

Honolulu, Hawaii 96817

United States

Ep0162 50512

Boise, Idaho 83702

United States

Ep0162 50493

Chicago, Illinois 60611

United States

Ep0162 50375

Springfield, Illinois 62702

United States

Ep0162 50504

Fort Wayne, Indiana 46804

United States

Ep0162 50561

Lexington, Kentucky 40536

United States

Ep0162 50395

New Orleans, Louisiana 70121

United States

Ep0162 50517

New Orleans, Louisiana 70122

United States

Ep0162 50093

Baltimore, Maryland 21287

United States

Ep0162 50488

Bethesda, Maryland 20817

United States

Ep0162 50615

Boston, Massachusetts 02118

United States

Ep0162 50047

Boston, Massachusetts 02215

United States

Ep0162 50110

Ann Arbor, Michigan 48109

United States

Ep0162 50507

St Louis, Missouri 63110

United States

Ep0162 50499

Las Vegas, Nevada 89128

United States

Ep0162 50626

Neptune City, New Jersey 07753

United States

Ep0162 50299

New Brunswick, New Jersey 08901

United States

Ep0162 50497

Buffalo, New York 14221

United States

Ep0162 50625

New Hyde Park, New York 11042

United States

Ep0162 50298

New York, New York 10016

United States

Ep0162 50490

New York, New York 10029

United States

Ep0162 50518

New York, New York 10075

United States

Ep0162 50034

Rochester, New York 14642

United States

Ep0162 50514

Charlotte, North Carolina 28204

United States

Ep0162 50487

Charlotte, North Carolina 28207

United States

Ep0162 50715

Durham, North Carolina 27705

United States

Ep0162 50371

Akron, Ohio 44308

United States

Ep0162 50528

Cleveland, Ohio 44195

United States

Ep0162 50724

Portland, Oregon 97227

United States

Ep0162 50510

Portland, Oregon 97239-3098

United States

Ep0162 50701

Portland, Oregon 97239

United States

Ep0162 50096

Philadelphia, Pennsylvania 19104

United States

Ep0162 50364

Philadelphia, Pennsylvania 19107

United States

Ep0162 50089

Philadelphia, Pennsylvania 19140

United States

Ep0162 50511

Pittsburgh, Pennsylvania 15212

United States

Ep0162 50491

Pittsburgh, Pennsylvania 15213

United States

Ep0162 50700

Chattanooga, Tennessee 37403

United States

Ep0162 50513

Memphis, Tennessee 38103-2800

United States

Ep0162 50103

Nashville, Tennessee 37232

United States

Ep0162 50731

Austin, Texas 78749

United States

Ep0162 50714

Houston, Texas 77030

United States

Ep0162 50525

Houston, Texas 77459

United States

Ep0162 50496

Round Rock, Texas 78681

United States

Ep0162 50473

Salt Lake City, Utah 84132

United States

Ep0162 50726

Winchester, Virginia 22601

United States

Ep0162 30016

Fitzroy,

Australia

Ep0162 30030

Herston,

Australia

Ep0162 30027

Melbourne,

Australia

Ep0162 30031

South Brisbane,

Australia

Ep0162 40650

Blagoevgrad,

Bulgaria

Ep0162 40708

Pazardzhik,

Bulgaria

Ep0162 40665

Pleven,

Bulgaria

Ep0162 40709

Pleven,

Bulgaria

Ep0162 40651

Sofia,

Bulgaria

Ep0162 20128

Beijing,

China

Ep0162 20246

Beijing,

China

Ep0162 20268

Beijing,

China

Ep0162 20299

Beijing,

China

Ep0162 20261

Changchun,

China

Ep0162 20133

Chengdu,

China

Ep0162 20137

Chengdu,

China

Ep0162 20250

Chongqing,

China

Ep0162 20334

Chongqing,

China

Ep0162 20179

Fuzhou,

China

Ep0162 20124

Guangzhou,

China

Ep0162 20260

Guangzhou,

China

Ep0162 20264

Guangzhou,

China

Ep0162 20269

Guangzhou,

China

Ep0162 20300

Guangzhou,

China

Ep0162 20022

Hangzhou,

China

Ep0162 20320

Kunming,

China

Ep0162 20258

Lanzhou,

China

Ep0162 20253

Nanchang,

China

Ep0162 20267

Nanjing,

China

Ep0162 20331

Nanning,

China

Ep0162 20333

Qingdao,

China

Ep0162 20123

Shanghai,

China

Ep0162 20292

Shanghai,

China

Ep0162 20332

Shenzhen,

China

Ep0162 20289

Shijiazhuang,

China

Ep0162 20119

Suzhou,

China

Ep0162 20257

Tianjin,

China

Ep0162 20025

Wenzhou,

China

Ep0162 20252

Wuhan,

China

Ep0162 20255

Yinchuan,

China

Ep0162 20262

Zhanjiang,

China

Ep0162 20251

Zhengzhou,

China

Ep0162 40670

Brno,

Czechia

Ep0162 40672

Ostrava - Poruba,

Czechia

Ep0162 40063

Prague,

Czechia

Ep0162 40671

Prague,

Czechia

Ep0162 40714

Prague,

Czechia

Ep0162 40681

Bron,

France

Ep0162 40688

Bron,

France

Ep0162 40680

Dijon,

France

Ep0162 40130

Marseille,

France

Ep0162 40019

Paris,

France

Ep0162 40682

Paris,

France

Ep0162 40201

Rennes,

France

Ep0162 40199

Strasbourg,

France

Ep0162 40577

Aachen,

Germany

Ep0162 40683

Berlin,

Germany

Ep0162 40685

Bielefeld,

Germany

Ep0162 40023

Erlangen,

Germany

Ep0162 40645

Frankfurt am Main,

Germany

Ep0162 40689

Kehl-kork,

Germany

Ep0162 40529

Marburg,

Germany

Ep0162 40724

München,

Germany

Ep0162 40666

Balassagyarmat,

Hungary

Ep0162 40673

Budapest,

Hungary

Ep0162 40704

Budapest,

Hungary

Ep0162 40653

Debrecen,

Hungary

Ep0162 40690

Catanzaro,

Italy

Ep0162 40674

Genova,

Italy

Ep0162 40144

Milan,

Italy

Ep0162 40477

Pavia,

Italy

Ep0162 40257

Roma,

Italy

Ep0162 40675

Roma,

Italy

Ep0162 20248

Fukuoka,

Japan

Ep0162 20070

Hachioji-shi,

Japan

Ep0162 20237

Hamamatsu,

Japan

Ep0162 20249

Hiroshima,

Japan

Ep0162 20236

Hōfu,

Japan

Ep0162 20239

Itami,

Japan

Ep0162 20143

Kodaira,

Japan

Ep0162 20315

Koshi-shi,

Japan

Ep0162 20147

Kyoto,

Japan

Ep0162 20243

Nagakute,

Japan

Ep0162 20235

Nagoya,

Japan

Ep0162 20238

Niigata,

Japan

Ep0162 20302

Osaka,

Japan

Ep0162 20241

Ōmura,

Japan

Ep0162 20316

Sapporo,

Japan

Ep0162 20337

Shimotsuga-gun,

Japan

Ep0162 20297

Shinjuku-ku,

Japan

Ep0162 20240

Shizuoka,

Japan

Ep0162 20242

Suita,

Japan

Ep0162 20266

Tōon,

Japan

Ep0162 20244

Yamagata,

Japan

Ep0162 40707

Bydgoszcz,

Poland

Ep0162 40677

Gdansk,

Poland

Ep0162 40219

Krakow,

Poland

Ep0162 40502

Krakow,

Poland

Ep0162 40842

Krakow,

Poland

Ep0162 40676

Lublin,

Poland

Ep0162 40091

Nowa Sól,

Poland

Ep0162 40153

Poznan,

Poland

Ep0162 40678

Świdnik,

Poland

Ep0162 40160

Barcelona,

Spain

Ep0162 40157

L'Hospitalet de Llobregat,

Spain

Ep0162 40540

Madrid,

Spain

Ep0162 40352

Pamplona,

Spain

Ep0162 40668

Seville,

Spain

Ep0162 40453

Terrassa,

Spain

Ep0162 40230

Valencia,

Spain

Ep0162 40667

Valladolid,

Spain

Ep0162 40686

Birmingham,

United Kingdom

Ep0162 40300

Cardiff,

United Kingdom

Ep0162 40735

Glasgow,

United Kingdom

Ep0162 40833

London,

United Kingdom

Ep0162 40163

Oxford,

United Kingdom

Ep0162 40108

Salford,

United Kingdom