This is a Retrospective Study on the Use of CENOBAMATE as Adjunctive Treatment in Patients Suffering From Epilepsy in Early Access Program in Germany, France and UK

Study Overview
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Brief Summary
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Cenobamate is a newly-FDA and EMA approved drug used to treat -focal-onset seizures in adult patients. The aim of the current study is to analyse retrospectively the overall effectiveness and tolerability of cenobamate from real-world data collected in patients who partecipated in the Early Access Program (EAP) and were treated with cenobamate as adjunctive ASM.

Detailed Description
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Cenobamate is a new approved drug used to treat -focal-onset seizures in adult patients. This novel tetrazole-derived carbamate seems to act primarily by two mechanisms that are commonly associated with epilepsy: cenobamate acts as a positive allosteric modulator of the GABAA ion channels and is effective in reducing repetitive neuronal firing by inhibition of voltage-gated sodium channels, although the complete mechanism of action is currently unknown. In clinical trials, cenobamate showed also low toxicity and adverse drug reaction profile. In European Union (EU), cenobamate received the marketing authorisation, valid throughout the EU, in March 2021. Starting from September 2020 an EAP was initiated with cenobamate as adjunctive ASM in several EU Countries such as Germany, France, and UK. Real-world data are of importance to understand and confirm the efficacy and safety profile of drugs outside of the clinical trial setting. The aim of the current study is to analyse the overall effectiveness and tolerability of cenobamate from real-world data in a large series of patients treated with cenobamate as adjunctive ASM. As a consequence, a retrospective collection and analysis of the data of the patients who participated in the EAP, according to the authorization received from the local regulatory or ethic authorities, was conducted.

Official Title
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Retrospective Study on the Use of CENOBAMATE as Adjunctive Treatment in a Cohort of Patients Suffering From Epilepsy With Focal Onset Seizure (FOS) and Enrolled Into the Early Access Program (EAP) in Germany, France and UK

Conditions
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Focal Onset Seizure, Epilepsy

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Data from adult patients diagnosed with epilepsy with FOS participating in the EAP with cenobamate as adjunctive treatment, according to the authorization received from the local regulatory or ethic authorities will be collected and analyzed. Available data will be collected after obtaining consent from patient/legal representative to the processing of personal data according to the General Data Protection Regulation (GDPR) and applicable local regulation Exclusion Criteria: Patient enrolled in other clinical trial during the EAP. Patient aged less than 18 years old. Patient with specific syndrome (e.g. LGS and Dravet)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort 1<br>Cohort of patients suffering from epilepsy with Focal Onset Seizure (FOS) and enrolled into the Early Access Program (EAP) in Germany, France and UK | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder rate (%) at 3 months from the start of maintenance | Percentage of responder rate (defined as a ≥50% reduction from screening/baseline in focal onset seizure frequency) after 3 months of maintenance phase. | 3 months from the start of maintenance | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Portion of responders | Portion of responders (defined as a ≥50% and <100% reduction from screening/baseline in focal onset seizure frequency) at 1 and 3 months after start of cenobamate therapy | 1 and 3 months after start of cenobamate therapy | 
| Portion of responders | Portion of responders (defined as a ≥50% and <100% reduction from screening/baseline in focal onset seizure frequency) at 3, 6 and 12 months after the completion of the titration and its relation with the dosage. | 3, 6 and 12 months after the completion of the titration and its relation with the dosage. | 
| Portion of seizure free | Portion of seizure free (100% reduction from screening/baseline) 1 and 3 months after start of cenobamate therapy | 1 and 3 months after start of cenobamate therapy | 
| Portion of seizure free | Portion of seizure free (100% reduction from screening/baseline)3, 6 and 12 months after the completion of the titration and its relation with the dosage. | 3, 6 and 12 months after the completion of the titration and its relation with the dosage. | 
| Retention rate | Retention rate measured as percentage of patients remaining in the study and on adjunctive therapy at: 1 and 3 months after start of cenobamate therapy | 1 and 3 months after start of cenobamate therapy | 
| Retention rate | Retention rate measured as percentage of patients remaining in the study and on adjunctive therapy at 3, 6 and 12 months after the completion of the titration and its relation with the dosage. | 3, 6 and 12 months after the completion of the titration | 
| No. of Adverse Reactions (ADRs), | Adverse Reactions (ADRs), including DRESS, rash/hypersensitivity occurred during the EAP. | Through study completion, an average of 2 years | 
| Change in Seizures Frequency | Change in Seizures Frequency at 1 and 3 months after start of cenobamate therapy, | 1 and 3 months after start of cenobamate therapy | 
| Change in Seizures Frequency | Change in Seizures Frequency at 3, 6 and 12 months after the completion of the titration | 3, 6 and 12 months after the completion of the titration | 
| Assessment of quality of life | The quality of life was assessed through the Questionnaire Quality of Life in Epilepsy Inventory - 31 items | 1 and 3 months after start of cenobamate therapy | 
| Assessment of quality of life | The quality of life was assessed through the Questionnaire Quality of Life in Epilepsy Inventory - 31 items | 3, 6 and 12 months after the completion of the titration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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epilepsy, FOS, cenobamate, retrospective, Early Access Program, Europe