Adjunctive Anti-seizure Medication (ASM) Real World Evidence (RWE) Study

A 12-month, Prospective, Observational Study in Adult Patients With Focal Onset Seizures Who Are Treated With Adjunctive ASM in Real World Setting

The purpose of this study is to describe the effectiveness of the adjunctive ASM treatment on the clinical response, safety profile and quality of life of patients affected by focal onset seizures in a real-world setting.

Study Overview

• Status: Active, not recruiting
• Conditions: Epilepsy
• Intervention / Treatment: Other: ASM as adjunctive therapy

Detailed Description

The aim of the study is to assess the effectiveness and safety of adjunctive therapy in a real-world setting of patients affected by focal-onset seizures who are eligible to start the treatment with ASM as adjunctive therapy according to the physician's judgment.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20133
    • Fondazione IRCCS Istituto Neurologico "Carlo Besta" U.O. Epilettologia Clinica e Sperimentale - Centro di Medicina del Sonno

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Adult patients with epilepsy having focal-onset seizures with or without secondary generalization not adequately controlled despite a history of treatment with at least 2 anti-seizure medications and who will meet all the inclusion and none of the exclusion study criteria.

The patients should be eligible to start a treatment with ASM as adjunctive therapy according to the physician's judgement, that must be clearly separated from the physician's decision to include the patient in the current study. The patients will be prospectively observed up to 12 months after having completed the related titration.

Description

Inclusion Criteria:

• Male and female patients of any ethnic origin ≥18 years old at baseline.
• Patients with diagnosis of focal-onset seizures with or without secondary generalization.
• Patients should have been eligible to start treatment with ASM as adjunctive therapy according to the physician's judgement prior to the inclusion.
• Patients should have clinical history of treatment failure with at least 2 ASMs.
• Patients using their seizure diary as part of their standard of care for at least 3 months prior to -the study entry (diary can be paper or electronic, filled in by patient and/or family members).
• Written informed consent (including data privacy consent) signed by the patient, legal guardian, or legally authorized representative prior to entering the study in accordance with the ICH GCP guidelines

Exclusion Criteria:

• Patients who meet any of the contraindications to the administration of adjunctive ASMs according to their approved SmPC.
• Progressive neurological disease, including degenerative CNS diseases and progressive tumors.
• Patients with unstable psychiatric diagnosis that may confound participants' ability to participate in the study or that may prevent completion of the protocol-specified assessments (e.g., in the judgement of the Investigator, pose an appreciable risk for suicide, including suicidal behavior and ideation within 6 months prior to enrollment, current psychotic disorder, acute mania).
• Evidence of clinically significant disease (e.g., cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the Investigator could affect the participant's safety or interfere with study assessments.
• Patients with substance abuse or dependence (except for caffeine and nicotine).
• Patients participating in any pharmacological or nonpharmacological interventional study within 30 days prior to baseline.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Adult patients with focal-onset seizures starting a treatment with ASM as adjunctive therapy; Adult patients having focal-onset seizures not adequately controlled despite a history of treatment with at least 2 ASM. The patients should be eligible to start a treatment with ASM as adjunctive therapy.The patients will be prospectively observed up to 12 months after having completed the related titration.

Other: ASM as adjunctive therapy; ASM approved as adjunctive therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in seizure frequency at 6 months of maintenance	The effectiveness of adjunctive ASM is measured as change in seizure frequency at 6 months of maintenance compared to baseline	At 6 months of maintenance compared to baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in seizure frequency at 3, 9, 12 months of maintenance	The effectiveness of adjunctive ASM is measured as change in seizure frequency at 3, 9, 12 months of maintenance compared to baseline	At 3, 9, 12 months of maintenance compared to baseline
50, 75, 90 Percent Responder rate	The effectiveness is measured as 50, 75, 90 Percent Responder rate	At 3, 6, 9, and 12 months of maintenance phase.
100 Percent Responder rate	The effectiveness is measured as number/percentage of seizure free patients	At 3, 6, 9, and 12 months of maintenance phase.
Retention rate	The effectiveness is measured as percentage of patients remaining in the study and on adjunctive therapy	At 3, 6, 9, and 12 months of maintenance phase.
Anxiety assessment	The assessment is measured by means of the Generalized Anxiety Disorder (GAD-7) scale. Scoring GAD-7 Anxiety Severity is calculated by assigning scores of 0, 1, 2, and 3 to the response categories, respectively, of "not at all," "several days," "more than half the days," and "nearly every day." GAD-7 total score for the seven items ranges from 0 to 21. 0-4: minimal anxiety 5-9: mild anxiety 10-14: moderate anxiety 15-21: severe anxiety.	At baseline, immediately after completion of titration, at 3 months, 6 months, and 12 months of maintenance phase.
Depression assessment	The assessment is measured through the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) scale. This is a validated screening tool for depression in patients with epilepsy that consists of a 6- item questionnaire. NDDI-E scores greater than 15 were considered positive for depression, as this score was previously shown to have a specificity of 90%, sensitivity of 81%, and positive predictive value of 0.62 for a diagnosis of major depression.	At baseline, immediately after completion of titration, at 3 months, 6 months, and 12 months of maintenance phase.
Quality of life (QOL)	The quality of life is measured by means the Quality Of Life In Epilepsy (QOLIE-31-P) questionnaire. This is a 38 questions survey of health-related quality of life for adults (18 years or older) with epilepsy. This version differs from the original QOLIE-31 (version 1) in the addition of questions about how much distress you feel about problems and worries related to epilepsy. This questionnaire should be completed only by the person who has epilepsy (not a relative or friend). Patients are asked to answer every question by circling the appropriate number (1, 2, 3...).	At baseline, immediately after completion of titration, at 3 months, 6 months, and 12 months of maintenance phase.
Cognitive assessment	The assessment of perceived cognitive deficits is measured through the Perceived Deficits Questionnaire (PDQ-5). The PDQ-5 assesses cognitive dysfunction in people with depression. This patient-reported questionnaire includes five items measuring attention/concentration, retrospective memory, prospective memory, and planning/organization over the past four weeks. The total score ranges from 0 to 20; higher scores indicate greater perceived cognitive dysfunction.	At baseline, immediately after completion of titration, at 3 months, 6 months, and 12 months of maintenance phase.
Adverse events (AEs)	Number of Adverse events (AEs) occurred (including AEs of special interest as Drug Reaction with Eosinophilia and Systemic Symptoms, rash/hypersensitivity, etc.).	Through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Aziende Chimiche Riunite Angelini Francesco S.p.A
• Collaborators: Hippocrates Research

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2023
• Primary Completion (Estimated): September 30, 2025
• Study Completion (Estimated): September 30, 2025

Study Registration Dates

• First Submitted: March 21, 2023
• First Submitted That Met QC Criteria: May 17, 2023
• First Posted (Actual): May 19, 2023

Study Record Updates

• Last Update Posted (Estimated): September 10, 2025
• Last Update Submitted That Met QC Criteria: September 3, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Epilepsy; Adjunctive Therapy; Focal-onset seizure; Cenobamate
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Epilepsy; Seizures
• Other Study ID Numbers: 169(A)MD21254

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No