A Study to Test the Efficacy and Safety of Staccato Alprazolam in Study Participants 12 Years of Age and Older With Stereotypical Prolonged Seizures
- Conditions
- Stereotypical Prolonged Seizures
- Interventions
- Other: Placebo
- Registration Number
- NCT05077904
- Lead Sponsor
- UCB Biopharma SRL
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 350
-
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:
- Generalized seizure episodes starting with a flurry of absence seizures or myoclonic seizures with a minimum total duration of 5 minutes
- Episodes of a focal seizure with a minimum duration of 3 minutes
- 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:
- 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
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Staccato alprazolam Arm Staccato alprazolam Participants randomized to this arm will receive a single dose of Staccato alprazolam by inhalation. Placebo Arm Placebo Participants randomized to this arm will receive a single dose of placebo by inhalation.
- Primary Outcome Measures
Name Time Method Treatment success for the treated seizure within 90 seconds after investigational medicinal product (IMP) administration From start of IMP treatment through 6 hours Treatment success for the treated seizure is defined as termination of the seizure within 90 seconds after IMP administration.
Treatment success for the treated seizure with no recurrence up to 2 hours From start of IMP treatment through 2 hours Treatment success for the treated seizure is defined as termination of the treated seizure within 90 seconds after IMP administration and no recurrence of seizure(s) from IMP administration to 2 hours after IMP administration and no initiation of seizure rescue treatment from 90 seconds to 2 hours after IMP administration.
- Secondary Outcome Measures
Name Time Method Number of subsequent seizure(s) up to 2 hours after IMP administration From start of IMP treatment through 2 hours The number of subsequent seizure(s) will be assessed up to 2 hours after IMP administration.
Treatment success for treated seizure with no recurrence after 4 hours From start of IMP treatment through 4 hours Treatment success defined as termination of the treated seizure within 90 seconds after IMP administration, with no recurrence of seizure(s) up to 4 hours after IMP administration and no initiation of seizure rescue treatment from 90 seconds to 4 hours after IMP administration.
Treatment success for treated seizure with no recurrence after 6 hours From start of IMP treatment through 6 hours Treatment success defined as termination of the treated seizure within 90 seconds after IMP administration, with no recurrence of seizure(s) up to 6 hours after IMP administration and no initiation of seizure rescue treatment from 90 seconds to 6 hours after IMP administration.
Time from IMP administration to cessation of the treated seizure From start of IMP treatment through 6 hours The time will be assessed from IMP administration to cessation of the treated seizure (taking administration of seizure rescue treatment as censoring point).
Frequency of respiratory treatment emergent adverse events (TEAEs) From start of IMP treatment up to the Safety Follow-up Visit (Week 19) An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of IMP, whether or not considered related to the IMP.
Time to first subsequent seizure up to 2 hours after IMP administration From start of IMP treatment through 2 hours The time to first subsequent seizure will be assessed up to 2 hours after IMP administration and is defined as time from end of IMP treated seizure to start of first subsequent seizure.
Trial Locations
- Locations (162)
Ep0162 20316
🇯🇵Sapporo, Japan
Ep0162 20070
🇯🇵Shinjuku-ku, Japan
Ep0162 20297
🇯🇵Shinjuku-ku, Japan
Ep0162 20240
🇯🇵Shizuoka, Japan
Ep0162 20242
🇯🇵Suita, Japan
Ep0162 20266
🇯🇵Toon, Japan
Ep0162 20244
🇯🇵Yamagata, Japan
Ep0162 40707
🇵🇱Bydgoszcz, Poland
Ep0162 40677
🇵🇱Gdansk, Poland
Ep0162 40219
🇵🇱Krakow, Poland
Ep0162 40502
🇵🇱Krakow, Poland
Ep0162 40676
🇵🇱Lublin, Poland
Ep0162 40091
🇵🇱Nowa Sól, Poland
Ep0162 40153
🇵🇱Poznan, Poland
Ep0162 40678
🇵🇱Swidnik, Poland
Ep0162 40160
🇪🇸Barcelona, Spain
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 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 40714
🇨🇿Praha 4, Czechia
Ep0162 40063
🇨🇿Praha 5, Czechia
Ep0162 40671
🇨🇿Praha 6, Czechia
Ep0162 40681
🇫🇷Bron, France
Ep0162 40688
🇫🇷Bron, France
Ep0162 40680
🇫🇷Dijon, France
Ep0162 40130
🇫🇷Marseille Cedex 5, France
Ep0162 40019
🇫🇷Paris, France
Ep0162 40682
🇫🇷Paris, France
Ep0162 40201
🇫🇷Rennes, France
Ep0162 40199
🇫🇷Strasbourg Cedex, 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 40157
🇪🇸Hospitalet de Llobregat, Spain
Ep0162 40540
🇪🇸Madrid, Spain
Ep0162 40352
🇪🇸Pamplona, Spain
Ep0162 40668
🇪🇸Sevilla, Spain
Ep0162 40453
🇪🇸Terrassa, Spain
Ep0162 40230
🇪🇸Valencia, Spain
Ep0162 40667
🇪🇸Valladolid, Spain
Ep0162 40686
🇬🇧Birmingham, United Kingdom
Ep0162 40300
🇬🇧Cardiff, United Kingdom
Ep0162 40163
🇬🇧Oxford, United Kingdom
Ep0162 40108
🇬🇧Salford, United Kingdom
Ep0162 40708
🇧🇬Pazardzhik, Bulgaria
Ep0162 50506
🇺🇸Phoenix, Arizona, United States
Ep0162 30016
🇦🇺Fitzroy, Australia
Ep0162 30030
🇦🇺Herston, Australia
Ep0162 30027
🇦🇺Melbourne, Australia
Ep0162 30031
🇦🇺South Brisbane, Australia
Ep0162 40650
🇧🇬Blagoevgrad, Bulgaria
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 40704
🇭🇺Budapest, Hungary
Ep0162 40653
🇭🇺Debrecen, Hungary
Ep0162 40690
🇮🇹Catanzaro, Italy
Ep0162 40529
🇩🇪Marburg, Germany
Ep0162 40724
🇩🇪München, Germany
Ep0162 40666
🇭🇺Balassagyarmat, Hungary
Ep0162 40673
🇭🇺Budapest, Hungary
Ep0162 40674
🇮🇹Genova, Italy
Ep0162 40144
🇮🇹Milano, Italy
Ep0162 40477
🇮🇹Pavia, Italy
Ep0162 40257
🇮🇹Roma, Italy
Ep0162 40675
🇮🇹Roma, Italy
Ep0162 20248
🇯🇵Fukuoka, Japan
Ep0162 20237
🇯🇵Hamamatsu, Japan
Ep0162 20249
🇯🇵Hiroshima-shi, Japan
Ep0162 20315
🇯🇵Koshi, Japan
Ep0162 20236
🇯🇵Hofu, Japan
Ep0162 20239
🇯🇵Itami, Japan
Ep0162 20143
🇯🇵Kodaira, Japan
Ep0162 20147
🇯🇵Kyoto, Japan
Ep0162 20243
🇯🇵Nagakute, Japan
Ep0162 20235
🇯🇵Nagoya, Japan
Ep0162 20238
🇯🇵Niigata, Japan
Ep0162 20241
🇯🇵Omura, Japan
Ep0162 20302
🇯🇵Osaka, Japan
Ep0162 50494
🇺🇸Little Rock, Arkansas, United States
Ep0162 50118
🇺🇸Downey, California, United States
Ep0162 50505
🇺🇸Los Angeles, California, United States
Ep0162 50492
🇺🇸Orange, California, United States
Ep0162 50367
🇺🇸New Haven, Connecticut, United States
Ep0162 50088
🇺🇸Washington, District of Columbia, United States
Ep0162 50515
🇺🇸Gulf Breeze, Florida, United States
Ep0162 50508
🇺🇸Jacksonville, Florida, United States
Ep0162 50342
🇺🇸Jacksonville, Florida, United States
Ep0162 50199
🇺🇸Miami, Florida, United States
Ep0162 50509
🇺🇸Orlando, Florida, United States
Ep0162 50308
🇺🇸Tampa, Florida, United States
Ep0162 50323
🇺🇸Honolulu, Hawaii, United States
Ep0162 50512
🇺🇸Boise, Idaho, United States
Ep0162 50493
🇺🇸Chicago, Illinois, United States
Ep0162 50375
🇺🇸Springfield, Illinois, United States
Ep0162 50504
🇺🇸Fort Wayne, Indiana, United States
Ep0162 50561
🇺🇸Lexington, Kentucky, United States
Ep0162 50395
🇺🇸New Orleans, Louisiana, United States
Ep0162 50517
🇺🇸New Orleans, Louisiana, United States
Ep0162 50093
🇺🇸Baltimore, Maryland, United States
Ep0162 50488
🇺🇸Bethesda, Maryland, United States
Ep0162 50047
🇺🇸Boston, Massachusetts, United States
Ep0162 50110
🇺🇸Ann Arbor, Michigan, United States
Ep0162 50507
🇺🇸Saint Louis, Missouri, United States
Ep0162 50499
🇺🇸Las Vegas, Nevada, United States
Ep0162 50626
🇺🇸Neptune, New Jersey, United States
Ep0162 50299
🇺🇸New Brunswick, New Jersey, United States
Ep0162 50497
🇺🇸Buffalo, New York, United States
Ep0162 50298
🇺🇸New York, New York, United States
Ep0162 50490
🇺🇸New York, New York, United States
Ep0162 50518
🇺🇸New York, New York, United States
Ep0162 50034
🇺🇸Rochester, New York, United States
Ep0162 50514
🇺🇸Charlotte, North Carolina, United States
Ep0162 50487
🇺🇸Charlotte, North Carolina, United States
Ep0162 50371
🇺🇸Akron, Ohio, United States
Ep0162 50528
🇺🇸Cleveland, Ohio, United States
Ep0162 50510
🇺🇸Portland, Oregon, United States
Ep0162 50096
🇺🇸Philadelphia, Pennsylvania, United States
Ep0162 50364
🇺🇸Philadelphia, Pennsylvania, United States
Ep0162 50089
🇺🇸Philadelphia, Pennsylvania, United States
Ep0162 50511
🇺🇸Pittsburgh, Pennsylvania, United States
Ep0162 50491
🇺🇸Pittsburgh, Pennsylvania, United States
Ep0162 50513
🇺🇸Memphis, Tennessee, United States
Ep0162 50103
🇺🇸Nashville, Tennessee, United States
Ep0162 50525
🇺🇸Houston, Texas, United States
Ep0162 50496
🇺🇸Round Rock, Texas, United States
Ep0162 50473
🇺🇸Salt Lake City, Utah, United States