Clinical trial • Neurology

ALPRAZOLAM for Stereotypical prolonged seizure

Clinical trial of ALPRAZOLAM for Stereotypical prolonged seizure.

Overview

Trial Therapeutic Area
Neurology
Trial Disease
Stereotypical prolonged seizure
Drug Modality
Small molecule
Paediatric Trial
Yes

Key dates

Initial CTIS Submission Date
02-08-2024
First CTIS Authorization Date
04-09-2024

Trial design

Randomised, placebo matching staccato® alprazolam (no active substance) (placebo arm)-controlled trial in Italy, Bulgaria, Czechia and others.

Randomised
Yes
Comparator
Placebo matching Staccato® alprazolam (no active substance) (placebo arm)
Target Sample Size
224

Eligibility

Recruits 224 paediatric patients.

Pregnancy Exclusion
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
Vulnerable Population
The trial includes adolescents (participants ≥12 years). Consent/assent handling: participants capable of giving signed informed consent provide consent; minors provide assent where required and the informed consent form (ICF) or a specific assent form will be signed and dated by minors. A study caregiver (≥18 years) must be identified at screening and the caregiver must be capable of giving signed informed consent; legally authorized representatives (LARs) are permitted where applicable. Country-specific ICF/assent documents are provided (multiple language versions per country).

Inclusion criteria

  • {"criterion_text":"- 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: 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 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) A male participant must agree to use contraception during the Outpatient Treatment Period and for at least 7 days after investigational medicinal product (IMP) administration and refrain from donating sperm during this period b) 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 informed consent form (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 individualized participant management plan (iPMP)."}

Exclusion criteria

  • {"criterion_text":"- A history of alcohol or drug use disorder - A known hypersensitivity to any components of the IMP or comparable drugs (and/or an investigational device) or to albuterol (or similar bronchospasm rescue medication) - A diagnosis of atrial fibrillation or mitral stenosis - A history of convulsive status epilepticus in the 8 weeks prior to Screening - Has nonepileptic seizures indistinguishable from qualifying epileptic seizures - Has airway hypersensitivity and/or acute respiratory signs/symptoms - Has chronic pulmonary disorder other than mild asthma and/or recent history or presence of hemoptysis or pneumothorax - Tested positive for SARS-CoV-2 and experienced moderate to severe signs/symptoms of respiratory distress needing hospitalization or outpatient treatment such as ambulatory oxygen, treatment with inhaler medications, and/or oral medications for 4 weeks or more, unless resolved at least 6 months prior to Screening - Has experienced an upper respiratory tract infection within 4 weeks or bronchitis/pneumonia within 3 months of Screening - A history or presence of acute narrow-angle glaucoma - Has a condition where oral alprazolam is contraindicated - A history or presence of long QT syndrome, a family history of sudden death due to long QT syndrome, or unexplained syncope - Is taking any drug that is a strong CYP3A4 inhibitor, including azole antifungal agents (ketoconazole and itraconazole) and nefazodone - Is taking any opioids or sedative hypnotics on a chronic basis - Is taking nonselective beta blockers on a chronic basis - Is taking pharmacotherapy for an active psychiatric disorder and changes in regimen are anticipated during the study - Has laboratory abnormality that may increase risk associated with participation or may interfere with the interpretation of study results - Has an oxygen saturation <95 % (or less than normal in regions of altitude >2500 meters) for greater than 30 seconds during Screening. In case of an out-of-range result, 1 repeat will be allowed, if out of range again, the participant will be excluded - 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) -Has current unstable liver or biliary disease defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis - 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 ≥220msec, or any other electrocardiogram (ECG) abnormality i) The QTc is the QT interval corrected for heart rate according to Fridericia's formula (QTcF), either machine-read or manually over-read - A positive urine screen for drugs of abuse at Screening"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Treatment success for the treated seizure with no recurrence after 2 hours","definition_or_measurement_approach":"Measured as treatment success of a single administration of Staccato alprazolam versus placebo in rapidly terminating a seizure episode within 90 seconds and with no recurrence of seizure(s) up to 2 hours after IMP administration (per the main objective)."}

Secondary endpoints

  • {"endpoint_text":"- Treatment success for treated seizure with no recurrence after 4 hours","definition_or_measurement_approach":"Treatment success measured as no recurrence of the treated seizure episode up to 4 hours after IMP administration."}
  • {"endpoint_text":"- Treatment success for treated seizure with no recurrence after 6 hours","definition_or_measurement_approach":"Treatment success measured as no recurrence of the treated seizure episode up to 6 hours after IMP administration."}
  • {"endpoint_text":"- Time from IMP administration to cessation of the treated seizure","definition_or_measurement_approach":"Measured time interval from IMP administration to seizure cessation for the treated seizure episode."}
  • {"endpoint_text":"- Frequency of respiratory treatment emergent adverse events (TEAEs)","definition_or_measurement_approach":"Frequency/count of respiratory-related TEAEs observed after treatment (pulmonary safety evaluation of single dose vs placebo)."}
  • {"endpoint_text":"- Number of subsequent seizure(s) up to 2 hours after IMP administration","definition_or_measurement_approach":"Count of subsequent seizure events occurring within 2 hours post-IMP administration."}
  • {"endpoint_text":"- Time to first subsequent seizure up to 2 hours after IMP administration","definition_or_measurement_approach":"Time from IMP administration to first subsequent seizure within the 2-hour post-dose window."}

Recruitment

Registry Or Advocacy Recruitment
True; Epilepsy Study Consortium Inc.; Center For Information And Study On Clinical Research Participation Inc.
Digital Remote Recruitment
True; web-based recruitment pages, email outreach campaigns and online study information materials are provided (country-specific web/email documents present).
Planned Sample Size
224
Recruitment Window Months
43
Consent Approach
Informed consent is obtained from participants capable of providing signed consent; minors provide assent where required and the ICF or specific assent form will be signed and dated by minors. A study caregiver (≥18 years) must be identified at screening and the caregiver must be capable of giving signed informed consent; legally authorized representatives (LARs) are permitted. Consent/assent materials are provided in country-specific languages (country ICF documents and translations are present for each Member State listed).

Methods

  • Site-based recruitment materials and posters (country-specific versions: e.g. K2_ep0162-...-recr-poster files present for multiple countries).
  • Study website / web pages (documents named '*-recr-web-*-public' indicate web-based recruitment materials per country).
  • Email outreach (files named '*-recr-email-*-public' indicate email campaigns/materials per country).
  • Patient-facing printed materials / patient brochures and patient pack pages (files named '*-recr-pb-*', '*-recr-pp-*' present).
  • Site staff / clinician referral (site lists and trial sites provided for each country; site-level recruitment is planned).
  • Use of patient organisation / advocacy channels and consortium engagement (listed third parties include patient organisations and Epilepsy Study Consortium involvement).

Geography

Total Number Of Sites
44
Total Number Of Participants
126

Italy

Earliest CTIS Part Ii Submission Date
22-08-2024
Latest Decision Or Authorization Date
05-08-2025
Processing Time Days
348
Number Of Sites
6
Number Of Participants
12

Sites

Site Name
Fondazione Istituto Neurologico Nazionale Casimiro Mondino
Department Name
#40477:Regional Site for Epilepsy
Contact Person Name
Carlo Andrea Galimberti
Site Name
Azienda Ospedaliera Policlinico Universitario Tor Vergata
Department Name
#40257: Dermatologia
Contact Person Name
Francesca Izzi
Contact Person Email
fraizzi@tin.it
Site Name
Azienda Ospedaliero-Universitaria Policlinico Umberto I
Department Name
#40675: Neurologia
Contact Person Name
Carlo Di Bonaventura
Site Name
IRCCS Foundation Istituto Neurologico Carlo Besta
Department Name
#40144: U.O.C. Neurologia 7 Struttura Semplice Diagnostica Epilettologica Integrata
Contact Person Name
Laura Canafoglia
Site Name
IRCCS Ospedale Policlinico San Martino
Department Name
#40674: cardiologia
Contact Person Name
Flavio Villani
Contact Person Email
flavio.villani@hsanmartino.it
Site Name
Azienda Ospedaliera Universitaria Mater Domini
Department Name
#40690: UO Neurologia
Contact Person Name
Antonio Gambardella
Contact Person Email
a.gambardella@unicz.it

Bulgaria

Earliest CTIS Part Ii Submission Date
22-08-2024
Latest Decision Or Authorization Date
21-04-2026
Processing Time Days
607
Number Of Sites
4
Number Of Participants
23

Sites

Site Name
Military Medical Academy
Department Name
#40709: Neurology
Contact Person Name
Plamen Georgiev
Contact Person Email
tzvetanovplamen@hotmail.com
Site Name
Mnogoprofilna Bolnitsa Za Aktivno Lechenie Puls AD
Department Name
#40650: Department of Neurology
Contact Person Name
Sasho Kastrev
Contact Person Email
kastrev@hotmail.com
Site Name
Mnogoprofilna Bolnitsa Za Aktivno Lechenie Higiya AD
Department Name
#40708: Neurology
Contact Person Name
Hristina Chilingirova-Ignatieva
Contact Person Email
chilingirova.hristina@abv.bg
Site Name
Multiprofile Hospital For Active Treatment In Neurology And Psychiatry St. Naum EAD
Department Name
#40651: Epilepsy Department in the Clinic of Nerve Disorders for Paroxysmal States
Contact Person Name
Ivan Milanov
Contact Person Email
ubalnp@yahoo.com

Czechia

Earliest CTIS Part Ii Submission Date
22-08-2024
Latest Decision Or Authorization Date
23-02-2026
Processing Time Days
550
Number Of Sites
5
Number Of Participants
21

Sites

Site Name
Cerebrovaskularni poradna s.r.o.
Department Name
#40672
Contact Person Name
Michal Bar
Contact Person Email
michal.bar@fno.cz
Site Name
Fakultni Thomayerova nemocnice
Department Name
#40714: Neurologicka klinika
Contact Person Name
Dana Vyskocilova
Contact Person Email
dana.vyskocilova@ftn.cz
Site Name
Forbeli s.r.o.
Department Name
#40671
Contact Person Name
Michal Bajacek
Contact Person Email
mbajacek@yahoo.co.uk
Site Name
Fakultni Nemocnice V Motole
Department Name
#40063: Neurologicka klinika
Contact Person Name
Jana Zarubova
Contact Person Email
jana.zarubova@epileptolog.eu
Site Name
Fakultni Nemocnice U Sv Anny V Brne
Department Name
#40670: I. Neurologicka klinika
Contact Person Name
Jitka Kocvarova
Contact Person Email
jitka.krizova@fnusa.cz

Germany

Earliest CTIS Part Ii Submission Date
22-08-2024
Latest Decision Or Authorization Date
17-03-2026
Processing Time Days
572
Number Of Sites
6
Number Of Participants
8

Sites

Site Name
Diakonie Kork
Department Name
#40689
Contact Person Name
Bernhard Steinhoff
Contact Person Email
bsteinhoff@epilepsiezentrum.de
Site Name
Goethe University Frankfurt
Department Name
#40645: Zentrum für Neurologie und Neurochirurgie
Contact Person Name
Felix Rosenow
Contact Person Email
rosenow@med.uni-frankfurt.de
Site Name
Universitaetsklinikum Giessen und Marburg GmbH
Department Name
#40529: Klinik und Poliklinik für Neurologie
Contact Person Name
Susanne Knake
Contact Person Email
knake@med.uni-marburg.de
Site Name
Gesellschaft Fuer Epilepsieforschung
Department Name
#40685: Epilepsiezentrum Bethel
Contact Person Name
Christian Brandt
Contact Person Email
christian.brandt@mara.de
Site Name
Vivantes Netzwerk fuer Gesundheit GmbH
Department Name
#40683: Klinik für Neurologie
Contact Person Name
Bettina Schmitz
Contact Person Email
bettina.schmitz@vivantes.de
Site Name
Universitaetsklinikum Erlangen AöR
Department Name
#40023: Klinik für molekulare Neurologie
Contact Person Name
Hajo Hamer
Contact Person Email
hajo.hamer@uk-erlangen.de

Hungary

Earliest CTIS Part Ii Submission Date
22-08-2024
Latest Decision Or Authorization Date
12-03-2026
Processing Time Days
567
Number Of Sites
4
Number Of Participants
15

Sites

Site Name
Semmelweis University
Department Name
#40704: Tűzoltó utcai részleg
Contact Person Name
Kristóf Márk Farkas
Contact Person Email
kristofm.farkas@gmail.com
Site Name
Dr. Kenessey Albert Korhaz Rendelointezet
Department Name
#40666: Pulmonology
Contact Person Name
Viktor Bauer
Contact Person Email
dr.bauer.viktor@gmail.com
Site Name
University Of Debrecen
Department Name
#40653: Altalanos Gyermekgyogyaszat
Contact Person Name
Monika Bessenyei
Contact Person Email
besmoni@gmail.com
Site Name
Orszagos Mentalis Ideggyogyaszati Es Idegsebeszeti Intezet
Department Name
#40673: Juhász Pál Epilepszia Központ
Contact Person Name
Anna Kelemen
Contact Person Email
kelemenanna@hotmail.com

Poland

Earliest CTIS Part Ii Submission Date
22-08-2024
Latest Decision Or Authorization Date
25-03-2026
Processing Time Days
580
Number Of Sites
7
Number Of Participants
18

Sites

Site Name
Specjalistyczne Gabinety Lekarskie Landa
Department Name
#40842: Neurology
Contact Person Name
Magdalena Bosak
Contact Person Email
magdalenabosak@wp.pl
Site Name
Copernicus Podmiot Leczniczy Sp. z o.o.
Department Name
#40677: Oddzial Neurologiczny
Contact Person Name
Waldemar Fryze
Contact Person Email
w.fryze@wp.pl
Site Name
Twoja Przychodnia Nowosolskie Centrum Medyczne Sp. z o.o.
Department Name
#40091: Neurology
Contact Person Name
Agata Klosek
Contact Person Email
klosek@twojaprzychodnia.com
Site Name
Clinical Best Solutions Sp. z o.o. S.K.
Department Name
#40676: Neurology
Contact Person Name
Jacek Gawlowicz
Contact Person Email
gawlowiczj@wp.pl
Site Name
NZOZ IGNIS dr med. Alicja Lobinska
Department Name
#40678: Neurology
Contact Person Name
Alicja Lobinska
Contact Person Email
alalob@tlen.pl
Site Name
Centrum Medyczne Neuromed Sp. z o.o.
Department Name
#40707: Neurology
Contact Person Name
Pawel Lisewski
Contact Person Email
lisewski.p@gmail.com
Site Name
Centrum Medyczne Plejady Magdalena Celinska Loewenhoff Michal Zolnowski sp.k.
Department Name
#40502: Neurology
Contact Person Name
Marta Zolnowska
Contact Person Email
marta.zolnowska@gmail.com

Spain

Earliest CTIS Part Ii Submission Date
22-08-2024
Latest Decision Or Authorization Date
01-04-2026
Processing Time Days
587
Number Of Sites
7
Number Of Participants
23

Sites

Site Name
Hospital Universitario Y Politecnico La Fe
Department Name
#40230: Neurología Pediátrica
Contact Person Name
Vicente Villanueva Haba
Contact Person Email
villanueva_vichab@gva.es
Site Name
Centro De Neurologia Avanzada S.L.P.
Department Name
#40668: Neurología
Contact Person Name
Juan Rodriguez Uranga
Contact Person Email
uranganeuro@gmail.com
Site Name
Fundacio Assistencial De Mutua De Terrassa Fpc
Department Name
#40453: Unitat de Recerca de Neurologia
Contact Person Name
Belen Diaz Fernandez
Contact Person Email
Bdiaz@mutuaterrassa.cat
Site Name
Hospital Universitari Vall D Hebron
Department Name
#40160: Neurología
Contact Person Name
Manuel Toledo Argany
Contact Person Email
manuel.toledo@vallhebron.cat
Site Name
Hospital Ruber Internacional
Department Name
#40540: Neurology
Contact Person Name
Antonio Gil-Nagel
Contact Person Email
agnagel@neurologiaclinica.es
Site Name
Clinica Universidad De Navarra
Department Name
#40352: Neurología
Contact Person Name
Rocío Sánchez Carpintero Abad
Contact Person Email
rsanchezc@unav.es
Site Name
Bellvitge University Hospital
Department Name
#40157: Neurologia
Contact Person Name
Merce Falip Centellas
Contact Person Email
mfalip@bellvitgehospital.cat

France

Earliest CTIS Part Ii Submission Date
22-08-2024
Latest Decision Or Authorization Date
03-04-2026
Processing Time Days
589
Number Of Sites
5
Number Of Participants
6

Sites

Site Name
Les Hopitaux Universitaires De Strasbourg
Department Name
#40199: Service de Neurologie
Contact Person Name
Maria Paola VALENTI HIRSCH
Site Name
University Hospitals Pitie Salpetriere Charles Foix
Department Name
#40019: Neurology Department
Contact Person Name
Vincent NAVARRO
Contact Person Email
vincent.navarro@aphp.fr
Site Name
Centre Hospitalier Universitaire De Rennes
Department Name
#40201: Neurology
Contact Person Name
Anca Nica
Contact Person Email
anca.pasnicu@chu-rennes.fr
Site Name
Hospices Civils De Lyon
Department Name
#40681: Epilepsie, Sommeil et Explorat
Contact Person Name
Eleni Panagiotakaki
Site Name
Robert Debre University Hospital
Department Name
#40682: Service de Neurologie Pédiatrique
Contact Person Name
Stéphane Auvin
Contact Person Email
stephane.auvin@aphp.fr

Sponsor

Primary sponsor

Full Name
UCB Biopharma
Organisation Type
Pharmaceutical company
Country Of Registered Address
Belgium

Contract research organisations

Name
Longboat Clinical Limited
Responsibilities
Patient Recruitment
Name
Medidata Solutions Inc.
Name
Q Squared Solutions Limited
Responsibilities
Central laboratory
Name
Eresearchtechnology Inc.
Responsibilities
Central ECG reading
Name
RWS Life Sciences Inc.
Responsibilities
Scales & Linguistic validation services

Third parties

  • {"country":"United States","full_name":"RWS Life Sciences Inc.","duties_or_roles":"Scales & Linguistic validation services","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Veramed Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Ireland","full_name":"Longboat Clinical Limited","duties_or_roles":"Patient Recruitment","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Clinical Ink Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Epilepsy Study Consortium Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"Central laboratory","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Formedix Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Center For Information And Study On Clinical Research Participation Inc.","duties_or_roles":"","organisation_type":"Patient organisation/association"}
  • {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Central ECG reading","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
alprazolam
Active Substance
ALPRAZOLAM
Modality
Small molecule
Routes Of Administration
INHALATION USE
Route
INHALATION
Authorisation Status
Authorised
Frequency
Single administration
Maximum Dose
2 mg
Investigational Product Name
Placebo matching < Staccato® alprazolam > and without active substance
Modality
Other

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