Clinical trial NCT05077904: A Study to Test the Efficacy and Safety of Staccato Alprazolam in Study Participants 12 Years of Age and Older With Stereotypical Prolonged Seizures
Official title: A Double-Blind, Randomized, Placebo-Controlled, Multicenter, Outpatient, Parallel-Group Study to Assess the Efficacy and Safety of Staccato Alprazolam in Study Participants 12 Years of Age and Older With Stereotypical Prolonged Seizures
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Stereotypical Prolonged Seizures
Keywords: Stereotypical prolonged seizures
Phase 3
Staccato alprazolam
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2021-10-14
Enrollment: 350
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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: 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

Primary outcomes:
measure: Treatment success for the treated seizure within 90 seconds after investigational medicinal product (IMP) administration
timeFrame: From start of IMP treatment through 6 hours
measure: Treatment success for the treated seizure with no recurrence up to 2 hours
timeFrame: From start of IMP treatment through 2 hours
Secondary outcomes:
measure: Treatment success for treated seizure with no recurrence after 4 hours
timeFrame: From start of IMP treatment through 4 hours
measure: Treatment success for treated seizure with no recurrence after 6 hours
timeFrame: From start of IMP treatment through 6 hours
measure: Time from IMP administration to cessation of the treated seizure
timeFrame: From start of IMP treatment through 6 hours
measure: Frequency of respiratory treatment emergent adverse events (TEAEs)
timeFrame: From start of IMP treatment up to the Safety Follow-up Visit (Week 19)
measure: Number of subsequent seizure(s) up to 2 hours after IMP administration
timeFrame: From start of IMP treatment through 2 hours
measure: Time to first subsequent seizure up to 2 hours after IMP administration
timeFrame: From start of IMP treatment through 2 hours
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Ep0162 50506
state: Arizona
city: Little Rock
country: United States
facility: Ep0162 50494
state: Arkansas
city: Downey
country: United States
facility: Ep0162 50118
state: California
city: Long Beach
country: United States
facility: Ep0162 50702
state: California
city: Los Angeles
country: United States
facility: Ep0162 50505
state: California
city: Orange
country: United States
facility: Ep0162 50492
state: California
city: New Haven
country: United States
facility: Ep0162 50367
state: Connecticut
city: Washington
country: United States
facility: Ep0162 50088
state: District of Columbia
city: Gulf Breeze
country: United States
facility: Ep0162 50515
state: Florida
city: Jacksonville
country: United States
facility: Ep0162 50508
state: Florida
city: Jacksonville
country: United States
facility: Ep0162 50342
state: Florida
city: Miami
country: United States
facility: Ep0162 50199
state: Florida
city: Orlando
country: United States
facility: Ep0162 50509
state: Florida
city: Rockledge
country: United States
facility: Ep0162 50703
state: Florida
city: Tampa
country: United States
facility: Ep0162 50308
state: Florida
city: Honolulu
country: United States
facility: Ep0162 50323
state: Hawaii
city: Boise
country: United States
facility: Ep0162 50512
state: Idaho
city: Chicago
country: United States
facility: Ep0162 50493
state: Illinois
city: Springfield
country: United States
facility: Ep0162 50375
state: Illinois
city: Fort Wayne
country: United States
facility: Ep0162 50504
state: Indiana
city: Lexington
country: United States
facility: Ep0162 50561
state: Kansas
city: New Orleans
country: United States
facility: Ep0162 50395
state: Louisiana
city: New Orleans
country: United States
facility: Ep0162 50517
state: Louisiana
city: Baltimore
country: United States
facility: Ep0162 50093
state: Maryland
city: Bethesda
country: United States
facility: Ep0162 50488
state: Maryland
city: Boston
country: United States
facility: Ep0162 50047
state: Massachusetts
city: Ann Arbor
country: United States
facility: Ep0162 50110
state: Michigan
city: Saint Louis
country: United States
facility: Ep0162 50507
state: Missouri
city: Las Vegas
country: United States
facility: Ep0162 50499
state: Nevada
city: Neptune
country: United States
facility: Ep0162 50626
state: New Jersey
city: New Brunswick
country: United States
facility: Ep0162 50299
state: New Jersey
city: Buffalo
country: United States
facility: Ep0162 50497
state: New York
city: New York
country: United States
facility: Ep0162 50298
state: New York
city: New York
country: United States
facility: Ep0162 50490
state: New York
city: New York
country: United States
facility: Ep0162 50518
state: New York
city: Rochester
country: United States
facility: Ep0162 50034
state: New York
city: Charlotte
country: United States
facility: Ep0162 50514
state: North Carolina
city: Charlotte
country: United States
facility: Ep0162 50487
state: North Carolina
city: Akron
country: United States
facility: Ep0162 50371
state: Ohio
city: Cleveland
country: United States
facility: Ep0162 50528
state: Ohio
city: Portland
country: United States
facility: Ep0162 50510
state: Oregon
city: Philadelphia
country: United States
facility: Ep0162 50096
state: Pennsylvania
city: Philadelphia
country: United States
facility: Ep0162 50364
state: Pennsylvania
city: Philadelphia
country: United States
facility: Ep0162 50089
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Ep0162 50511
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Ep0162 50491
state: Pennsylvania
city: Memphis
country: United States
facility: Ep0162 50513
state: Tennessee
city: Nashville
country: United States
facility: Ep0162 50103
state: Tennessee
city: Houston
country: United States
facility: Ep0162 50525
state: Texas
city: Round Rock
country: United States
facility: Ep0162 50496
state: Texas
city: Salt Lake City
country: United States
facility: Ep0162 50473
state: Utah
city: Fitzroy
country: Australia
facility: Ep0162 30016
city: Herston
country: Australia
facility: Ep0162 30030
city: Melbourne
country: Australia
facility: Ep0162 30027
city: South Brisbane
country: Australia
facility: Ep0162 30031
city: Blagoevgrad
country: Bulgaria
facility: Ep0162 40650
city: Pazardzhik
country: Bulgaria
facility: Ep0162 40708
city: Pleven
country: Bulgaria
facility: Ep0162 40665
city: Pleven
country: Bulgaria
facility: Ep0162 40709
city: Sofia
country: Bulgaria
facility: Ep0162 40651
city: Beijing
country: China
facility: Ep0162 20128
city: Beijing
country: China
facility: Ep0162 20246
city: Beijing
country: China
facility: Ep0162 20268
city: Beijing
country: China
facility: Ep0162 20299
city: Changchun
country: China
facility: Ep0162 20261
city: Chengdu
country: China
facility: Ep0162 20133
city: Chengdu
country: China
facility: Ep0162 20137
city: Chongqing
country: China
facility: Ep0162 20250
city: Chongqing
country: China
facility: Ep0162 20334
city: Fuzhou
country: China
facility: Ep0162 20179
city: Guangzhou
country: China
facility: Ep0162 20124
city: Guangzhou
country: China
facility: Ep0162 20260
city: Guangzhou
country: China
facility: Ep0162 20264
city: Guangzhou
country: China
facility: Ep0162 20269
city: Guangzhou
country: China
facility: Ep0162 20300
city: Hangzhou
country: China
facility: Ep0162 20022
city: Kunming
country: China
facility: Ep0162 20320
city: Lanzhou
country: China
facility: Ep0162 20258
city: Nanchang
country: China
facility: Ep0162 20253
city: Nanjing
country: China
facility: Ep0162 20267
city: Nanning
country: China
facility: Ep0162 20331
city: Qingdao
country: China
facility: Ep0162 20333
city: Shanghai
country: China
facility: Ep0162 20123
city: Shanghai
country: China
facility: Ep0162 20292
city: Shenzhen
country: China
facility: Ep0162 20332
city: Shijiazhuang
country: China
facility: Ep0162 20289
city: Suzhou
country: China
facility: Ep0162 20119
city: Tianjin
country: China
facility: Ep0162 20257
city: Wenzhou
country: China
facility: Ep0162 20025
city: Wuhan
country: China
facility: Ep0162 20252
city: Yinchuan
country: China
facility: Ep0162 20255
city: Zhanjiang
country: China
facility: Ep0162 20262
city: Zhengzhou
country: China
facility: Ep0162 20251
city: Brno
country: Czechia
facility: Ep0162 40670
city: Ostrava - Poruba
country: Czechia
facility: Ep0162 40672
city: Praha 4
country: Czechia
facility: Ep0162 40714
city: Praha 5
country: Czechia
facility: Ep0162 40063
city: Praha 6
country: Czechia
facility: Ep0162 40671
city: Bron
country: France
facility: Ep0162 40681
city: Bron
country: France
facility: Ep0162 40688
city: Dijon
country: France
facility: Ep0162 40680
city: Marseille Cedex 5
country: France
facility: Ep0162 40130
city: Paris
country: France
facility: Ep0162 40019
city: Paris
country: France
facility: Ep0162 40682
city: Rennes
country: France
facility: Ep0162 40201
city: Strasbourg Cedex
country: France
facility: Ep0162 40199
city: Aachen
country: Germany
facility: Ep0162 40577
city: Berlin
country: Germany
facility: Ep0162 40683
city: Bielefeld
country: Germany
facility: Ep0162 40685
city: Erlangen
country: Germany
facility: Ep0162 40023
city: Frankfurt Am Main
country: Germany
facility: Ep0162 40645
city: Kehl-kork
country: Germany
facility: Ep0162 40689
city: Marburg
country: Germany
facility: Ep0162 40529
city: München
country: Germany
facility: Ep0162 40724
city: Balassagyarmat
country: Hungary
facility: Ep0162 40666
city: Budapest
country: Hungary
facility: Ep0162 40673
city: Budapest
country: Hungary
facility: Ep0162 40704
city: Debrecen
country: Hungary
facility: Ep0162 40653
city: Catanzaro
country: Italy
facility: Ep0162 40690
city: Genova
country: Italy
facility: Ep0162 40674
city: Milano
country: Italy
facility: Ep0162 40144
city: Pavia
country: Italy
facility: Ep0162 40477
city: Roma
country: Italy
facility: Ep0162 40257
city: Roma
country: Italy
facility: Ep0162 40675
city: Fukuoka
country: Japan
facility: Ep0162 20248
city: Hamamatsu
country: Japan
facility: Ep0162 20237
city: Hiroshima-shi
country: Japan
facility: Ep0162 20249
city: Hofu
country: Japan
facility: Ep0162 20236
city: Itami
country: Japan
facility: Ep0162 20239
city: Kodaira
country: Japan
facility: Ep0162 20143
city: Koshi
country: Japan
facility: Ep0162 20315
city: Kyoto
country: Japan
facility: Ep0162 20147
city: Nagakute
country: Japan
facility: Ep0162 20243
city: Nagoya
country: Japan
facility: Ep0162 20235
city: Niigata
country: Japan
facility: Ep0162 20238
city: Omura
country: Japan
facility: Ep0162 20241
city: Osaka
country: Japan
facility: Ep0162 20302
city: Sapporo
country: Japan
facility: Ep0162 20316
city: Shinjuku-ku
country: Japan
facility: Ep0162 20070
city: Shinjuku-ku
country: Japan
facility: Ep0162 20297
city: Shizuoka
country: Japan
facility: Ep0162 20240
city: Suita
country: Japan
facility: Ep0162 20242
city: Toon
country: Japan
facility: Ep0162 20266
city: Yamagata
country: Japan
facility: Ep0162 20244
city: Bydgoszcz
country: Poland
facility: Ep0162 40707
city: Gdansk
country: Poland
facility: Ep0162 40677
city: Krakow
country: Poland
facility: Ep0162 40219
city: Krakow
country: Poland
facility: Ep0162 40502
city: Lublin
country: Poland
facility: Ep0162 40676
city: Nowa Sól
country: Poland
facility: Ep0162 40091
city: Poznan
country: Poland
facility: Ep0162 40153
city: Swidnik
country: Poland
facility: Ep0162 40678
city: Barcelona
country: Spain
facility: Ep0162 40160
city: Hospitalet de Llobregat
country: Spain
facility: Ep0162 40157
city: Madrid
country: Spain
facility: Ep0162 40540
city: Pamplona
country: Spain
facility: Ep0162 40352
city: Sevilla
country: Spain
facility: Ep0162 40668
city: Terrassa
country: Spain
facility: Ep0162 40453
city: Valencia
country: Spain
facility: Ep0162 40230
city: Valladolid
country: Spain
facility: Ep0162 40667
city: Birmingham
country: United Kingdom
facility: Ep0162 40686
city: Cardiff
country: United Kingdom
facility: Ep0162 40300
city: Oxford
country: United Kingdom
facility: Ep0162 40163
city: Salford
country: United Kingdom
facility: Ep0162 40108
Study officials:
affiliation: 001 844 599 2273 (UCB)
name: UCB Cares
role: STUDY_DIRECTOR
References: