Safety and Tolerability of PTI5803 in Patients Aged 14 Years and Older With Drug‑Resistant Seizures Due to Focal Cortical Dysplasia

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What is this study about?

The study focuses on people aged 14 years and older who have drug‑resistant seizure activity caused by a brain abnormality known as focal cortical dysplasia. These seizures keep happening even though standard medicines have not been effective. The trial is testing an oral medication identified as PTI5803, which contains the active substance probenecid. The primary purpose is to determine whether this new treatment is safe and can be tolerated when added to the patients’ existing seizure medicines.

Participants will receive the study drug in a three‑step dose‑increase schedule, with each dose taken for several weeks. During the study, doctors will check vital signs, perform blood tests, and record heart rhythm using a simple test called a ECG. Researchers will also examine how the body absorbs and clears the medication (pharmacokinetics) and how the medication works in the body (pharmacodynamics). Throughout the trial, participants will keep a diary of their seizure events and complete questionnaires about their quality of life. After the initial phase, individuals may choose to continue in an optional open‑label extension where they can keep receiving the medication.

1 baseline assessments

after you join the study, you will undergo a series of initial evaluations. these include recording your seizure history, completing quality‑of‑life questionnaires, and having basic physical measurements such as blood pressure and heart rhythm checked. blood samples will be taken to measure the levels of any medicines you are already using and to establish a reference point for future laboratory tests.

2 start first dose of <b>pti5803</b>

you will begin taking pti5803, which contains the active ingredient probenecid. the medication is supplied as oral prolonged‑release granules and the prescribed amount is 16 ml taken once each day. the first dose level will be continued for approximately 28 days (allowable range ±7 days). during this period you will keep a daily seizure diary to record any seizure events and any side effects you notice.

3 monitoring visits during first dose

regular clinic visits will be scheduled while you are on the first dose. at each visit a clinician will review your seizure diary, ask about any adverse events, and repeat vital‑sign measurements. additional blood tests will be performed to check the concentration of probenecid and to monitor routine laboratory values such as liver and kidney function.

4 dose escalation to second level

if the first dose is tolerated, the study protocol will increase the amount of pti5803 to the next predefined level. the exact amount is determined by the study design, but the administration remains once daily by mouth. this second dose level will also be taken for about 28 days (±7 days). you will continue to record seizures and any side effects in your diary.

5 monitoring visits during second dose

the same type of safety and laboratory monitoring performed during the first dose will be repeated while you are on the second dose. the purpose is to detect any changes in vital signs, laboratory results, or seizure frequency that might be related to the increased dose.

6 dose escalation to third level

after successful completion of the second dose period, the medication will be increased to the third and highest dose level specified in the study. you will continue taking the dose once daily for another 28 days (±7 days). the seizure diary and reporting of any adverse events remain required.

7 monitoring visits during third dose

final safety assessments will be carried out during the third dose period. these include a repeat of vital‑sign checks, electrocardiogram (a test that records the heart’s electrical activity), laboratory blood tests, and review of your seizure diary. the investigators will also evaluate changes in the levels of any other anti‑seizure medicines you are using.

8 final study assessments

at the end of the three‑dose escalation phase, a comprehensive evaluation will be performed. this includes final questionnaires on quality of life, overall impression of change, and a summary of seizure frequency compared with the baseline period. all collected data will be used to assess the safety and early signs of effectiveness of pti5803.

9 optional open‑label extension

if you choose to continue, you may enter an optional extension study in which you will keep receiving pti5803 at the dose that was best tolerated. the extension follows the same monitoring schedule, with regular visits for safety checks, blood tests, and seizure tracking. participation in the extension is voluntary and may continue for an extended period as defined by the study protocol.

Who Can Join the Study?

Be a male or female aged between 14 and 55 years.
Sign an informed consent form (and a signed assent form if you are a minor) before any study procedures.
Agree to attend all required study visits and be able to keep an accurate seizure diary (a notebook where you write down each seizure and any study medication taken).
Have health insurance or meet the national legal requirements for participating in medical research.
Weigh at least 50 kg and have a body‑mass index (BMI) no higher than 40 kg/m² (BMI is a calculation that relates weight to height).
Have drug‑resistant seizures caused by focal cortical dysplasia (FCD) type I, II, or III, confirmed by an MRI scan or tissue test, diagnosed as epilepsy according to the 2017 International League Against Epilepsy (ILAE) criteria, and have had seizures for at least 2 years. “Drug‑resistant” means you have tried at least two antiseizure medicines at proper doses without achieving lasting seizure freedom.
Not have any major ongoing medical problems, as judged by the study doctor.
Experience at least 4 countable focal seizures (seizures that start in one part of the brain) on average every 28 days during the last three months, despite current treatment.
Be taking 1 to 3 antiseizure medications at stable doses for at least one month before joining the study. Use of a vagus nerve stimulator (VNS) device is allowed if it was implanted at least 6 months earlier, has stable settings for at least 3 months, and the battery is more than 25 % full.
If you are a female who could become pregnant, you must use a highly effective birth‑control method (failure rate less than 1 % per year) starting at least one month before signing consent and continue for about three months after the last study dose. Women who are not sexually active do not need to use birth control.
Females who cannot become pregnant (because they are surgically sterilized for at least 6 months or are post‑menopausal with no periods for at least 12 months) are also eligible.
Follow normal eating habits and have not been on a ketogenic diet (a high‑fat, low‑carbohydrate diet) for at least 3 months before joining.

Who Cannot Join the Study?

Taking long‑term medicines (other than anti‑seizure medicines) that cannot be changed because they may interact with probenecid, aspirin, methotrexate, sulfonylureas, or similar drugs.
Having abused drugs or alcohol excessively in the past year, or currently using substances that are considered abusive.
Having participated in another interventional clinical trial within the last month or until the previous study drug has cleared from the body (about five half‑lives).
Being allergic (hypersensitive) to probenecid or any ingredient of the study medication.
Being judged likely to not follow the study rules, being uncooperative, having a language barrier, or having severe intellectual disability.
Having severe kidney problems (kidney function measured as creatinine clearance less than 50 ml/min).
Having very high uric acid in the urine (≥700 mg per 24 hours) or a history of uric‑acid kidney stones (uric lithiasis).
Having high blood uric acid levels (>360 µmol/L for women or >420 µmol/L for men) (hyperuricemia).
Being infected with HIV.
Being pregnant, breastfeeding, or being under legal protection such as guardianship or curatorship.
Having a history of gout (painful joint condition caused by uric acid buildup).
Having psychogenic non‑epileptic seizures that would make counting seizure frequency unreliable.
Having a developmental and epileptic encephalopathy, including conditions like Lennox‑Gastaut syndrome.
Having a past history of stomach ulcers or being prone to significant stomach discomfort.
Having pre‑existing disorders of the blood‑forming system (haematopoietic disorders).
Planning to have any surgery during the study period.
Having undergone epilepsy surgery within the three months before enrollment.
Lacking effective contraception if sexually active (or being breastfeeding).
Having schizophrenia or other psychotic disorders.
Having attempted suicide in the past year or currently having suicidal thoughts, as identified by the C‑SSRS questionnaire.
Having any significant abnormal laboratory results, physical‑exam findings, or heart test (ECG) results that the investigator considers important.
Having any other major medical or surgical condition that is not well‑controlled, except for epilepsy surgery.

Where you can join this trial?

Verified and Recommended Sites

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Verified Sites

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Other Sites

Site Name	City	Country
Fondation A De Rothschild	Paris	France
Centre Hospitalier Lyon Sud	Pierre Benite	France
Ets Medical De La Teppe	Tain-L'hermitage	France
Abgslmdipa Ptpvsrex Hxfgpopm Dl Mvuosmlqz	Marseille	France

Trial status

Country	Status	Recruitment Start
France	Not yet recruiting	02.01.2027

Trial locations

PTI5803
PTI5803 is a medication taken by mouth in the form of prolonged‑release granules. It contains the active ingredient probenecid. In this study the drug is added to the patients’ usual seizure medicines (adjunctive therapy) and the dose is increased step by step over three levels. The purpose of using PTI5803 is to see if it is safe and well‑tolerated when given with other seizure drugs, to understand how the body absorbs and uses it, and to look for any early signs that it might help reduce drug‑resistant seizures caused by focal cortical dysplasia in people who are at least 14 years old.

Investigated Diseases:

Epilepsy

Drug-resistant epilepsy associated with focal cortical dysplasia – It is a type of epilepsy that does not respond well to standard medicines and is caused by a brain malformation called focal cortical dysplasia. Focal cortical dysplasia is an area where brain cells are abnormally organized, which can generate abnormal electrical activity. The seizures often begin in childhood or adolescence and may become more frequent over time. Because the seizures are resistant, they can persist despite attempts to control them, leading to ongoing episodes. The condition may evolve with changes in seizure patterns or severity as the brain develops.

Trial ID:

2026-525162-21-00

Protocol code:

A_CL_002

Trial Phase:

Therapeutic exploratory (Phase II)

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Safety and Tolerability of PTI5803 in Patients Aged 14 Years and Older With Drug‑Resistant Seizures Due to Focal Cortical Dysplasia

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?