Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Authorised, recruitment pending
Participants planned
192
Countries
1
Sites
11
Focal epilepsy
To assess the efficacy of PBN administration on the cessation of seizure recurrence in patients experiencing a cluster seizure upon discontinuation of ASM for pre-surgical hospital video EEG monitoring.
Key facts
- Sponsor
- Fondation A De Rothschild
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years, 18-64 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Nervous System Diseases [C10]
- Decision date (initial)
- 2025-10-17
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy
To assess the efficacy of PBN administration on the cessation of seizure recurrence in patients experiencing a cluster seizure upon discontinuation of ASM for pre-surgical hospital video EEG monitoring.
Secondary objectives 9
- The introduction of rescue treatment
- The time spent in seizures during the 4, 6 and 12 hours following the administration of treatment
- The occurrence of a tonic-clonic generalised seizure during the 12 hours following the administration of treatment
- The occurrence of status epilepticus during the 12 hours following the administration of treatment
- The appearance of a seizure-related lesion during the 12 hours following the administration of treatment
- The interictal activity
- The number of daily seizures during the remainder of the video-EEG monitoring period, starting 12 hours after treatment administration
- The effects on major vital signs between treatment administration and 2 hours after treatment administration
- The incidence of adverse and serious adverse events
Conditions and MedDRA coding
Focal epilepsy
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.1 | LLT | 10065337 | Focal epilepsy | 10029205 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Phase II multicenter randomized double-blinded placebo-controlled trial (ratio 1:1) After checking that the patient is eligible and obtaining signed consent from the patient or parents, video EEG monitoring begins in accordance to the standard care protocol, with reduction or non-reduction of anti-epileptic treatment. In case of SC defined as at least 2 epileptic seizures, lasting less than 10 minutes (validated by video-EEG recording) occurring in less than 6 hours, patients will be randomized in two groups. Randomization will be established in a 1:1 ratio by blocks of various sizes and stratified on inclusion center
|
Randomised Controlled | Double | [{"id":179005,"code":2,"name":"Investigator"},{"id":179006,"code":1,"name":"Subject"}] | Experimental arm: Oral administration of PBN at a dose of 3g in adults or children weighting > 50 kg; at a dose of 2g in children weighting 35 to 49 kg; and at a dose of 1g in children weighting 20 to 34 kg Control arm: Placebo administration in a scheme similar to experimental treatment |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 8
- Patients between 6 and 50 years old
- Children weighing at least 20 kg or adults weighing more than 50 kg
- With focal seizures epilepsy
- Requiring video-EEG recording in Epilepsy Monitoring Units (EMU) for the presurgical evaluation of a focal epilepsy, with planned Anti-Seizure Medication (ASM) withdrawal in order to precipitate seizure occurrence, or without dose reduction in the case of epilepsy whose natural history suggests the appearance of seizures without withdrawal.
- Able to take an oral therapy
- Ability to record the patient > 12 hours after the second seizure of the cluster
- Having received informed information about the study and having signed a consent form to participate in the study. Written consent of both holders of parental authority for minor patients
- Affiliated or beneficiary to a social security scheme
Exclusion criteria 10
- Hypersensitivity to PBN or to any of the excipients (Microcrystalline cellulose, Hypromellose, Sodium carboxymethylamidon, Colloidal anhydrous silica, Magnesium stearate)
- Known or identified impaired renal function (creatinine clearance < 50 ml/min) in children and adults
- Lithiasis diathesis
- Treatment with the following drugs: penicillins and other cephalosporins, acetylsalicylic acid, methotrexate, paracetamol, naproxen, indomethacin, ketoprofen, lorazepam, rifampicin, aciclovir, ganciclovir, zidovudine, sulfonamide
- Acute gout attack
- Hyperuricemia secondary to cancer chemotherapy, radiotherapy or myeloproliferative neoplasia
- Primary hyperuricemia due to overproduction of uric acid
- Participation in an interventional clinical study (drug, medical device, etc.)
- Patient benefiting from legal protection
- Pregnant or breast-feeding woman
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Proportion of patients without seizure between 60 min and 12h after PBN or placebo administration, assessed by the neurologist on video and EEG recording, in patients experiencing SC defined as at least 2 epileptic seizures lasting less than 10 min occurring in 6 hours or less during presurgical hospital videoEEG monitoring for focal epilepsy
Secondary endpoints 9
- Introduction of benzodiazepines or increase in weaned antiepileptic medication (if weaned) within 12 hours of treatment administration
- Time spent in seizure in minutes, assessed by the blinded neurologist on video and EEG recording
- Occurrence of tonic-clonic generalized seizure, assessed by the blinded neurologist on video and EEG recording
- Occurrence of a status epilepticus, assessed by the blinded neurologist on video and EEG recording
- Seizure-related injury (bone or tooth fracture, hematoma) assessed by the blinded neurologist
- Interictal activity quantified by the blinded neurologist on video and EEG recording as the evolution of the number of interictal spikes recorded during 15 minutes, 2 hours after treatment administration compared to the same period the day before
- Number of seizures during the rest of video EEG monitoring, assessed by the blinded neurologist on video and EEG recording
- Evolution of heart rate and blood pressure measurements from treatment administration to 2 hours post-administration
- Adverse and serious adverse events
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
SANTURIL 500 mg comprimé sécable
PRD7242186 · Product
- Active substance
- Probenecid
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 3 g gram(s)
- Max total dose
- 3 g gram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- M04AB01 — PROBENECID
- Marketing authorisation
- 34009 301 769 4 8
- MA holder
- LIPOMED GMBH
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Probenecid is used off-label in this context. In France, it is authorised for gout, a condition rare in children under 15. Its use in epilepsy for this age group is outside the approved Marketing Authorisation, although the product itself hasn’t been modified. Probenecid is FDA-approved in New Zealand and Sweden for gout-related hyperuricaemia and as an adjunct to antibiotics in children over 2 years (SmPCs).
Placebo 1
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Fondation A De Rothschild
- Sponsor organisation
- Fondation A De Rothschild
- Address
- 29 Rue Manin
- City
- Paris
- Postcode
- 75019
- Country
- France
Scientific contact point
- Organisation
- Fondation A De Rothschild
- Contact name
- Dr Amélie Yavchitz
Public contact point
- Organisation
- Fondation A De Rothschild
- Contact name
- Dr Amélie Yavchitz
Locations
1 EU/EEA country · 11 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Authorised, recruitment pending | 192 | 11 |
| Rest of world | — | 0 | — |
Investigational sites
Assistance Publique Hopitaux De Paris
Pediatric Neurology, 149 Rue De Sevres, 75015, Paris
Centre Hospitalier Universitaire De Rennes
Neurology, 2 Rue Henri Le Guilloux, 35000, Rennes
Centre Hospitalier Universitaire Rouen
Neurology, 1 Rue De Germont, Bp 96031, Rouen Cedex
Centre Hospitalier Universitaire De Lille
Neurology, Avenue Du Professeur Emile Laine, 59037, Lille Cedex
Centre Hospitalier Regional De Marseille
Epileptology and Cerebral Rhythmology, 264 Rue Saint Pierre, 13005, Marseille
Groupe Hospitalier Universitaire Paris Psychiatrie Et Neuroscience
Clinical neurophysiology, 1 Rue Cabanis, 75014, Paris
Centre Hospitalier Universitaire Grenoble Alpes
Neurology, Boulevard De La Chantourne, Cs 10217, Grenoble Cedex 9
Centre Hospitalier Universitaire De Toulouse
Neurophysiological explorations, 1 Place Du Docteur Joseph Baylac, 31300, Toulouse
Fondation A De Rothschild
Pediatric neurosurgery department, 29 Rue Manin, 75019, Paris
Fondation A De Rothschild
Neurology, 29 Rue Manin, 75019, Paris
Hospices Civils De Lyon
Functional Neurology and Epileptology, 59 Boulevard Pinel, 69500, Bron
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 10 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol_2024-519133-29-00_Clean | 2 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_TC | 1.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Ado_12-17 ans_Clean | 1.3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_adultes_Clean | 1.3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_enfants_6-11 ans_Clean | 1.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_parents_Clean | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_poursuite adultes_Clean | 1.2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC complement_Probenecide | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Probenecide | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_2024-519133-29-00 | 1.2 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2025-06-25 | France | Acceptable 2025-10-13
|
2025-10-17 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2026-04-01 | France | Acceptable 2026-04-27
|
2026-05-19 |