Cenobamate in Adults With Focal-Onset Seizures

Seizure frequency during the baseline and post-baseline assessments was calculated by summing the total number of seizures (all types of seizures) reported in each considered period and dividing by the duration of that period (number of days), excluding days with no available diary data, and multiplying by 28 to normalize to a monthly rate ("monthly seizure frequency").

Seizure frequency during the baseline and post-baseline assessments was calculated by summing the total number of seizures (all types of seizures) reported in each considered period and dividing by the duration of that period (number of days), excluding days with no available diary data, and multiplying by 28 to normalize to a monthly rate ("monthly seizure frequency").

Intra-patient percent change from baseline will be defined as [(monthly seizure frequency at post-baseline assessments - monthly seizure frequency at baseline), divided by the monthly seizure frequency at baseline] multiplied by 100.

Seizure frequency during the baseline and post-baseline assessments was calculated by summing the total number of seizures (all types of seizures) reported in each considered period and dividing by the duration of that period (number of days), excluding days with no available diary data, and multiplying by 28 to normalize to a monthly rate ("monthly seizure frequency").

Population will be stratified according to the following:

• Age class of patient at the time of cenobamate treatment initiation (i.e., <65 years; ≥65 years).
• Setting of cenobamate treatment initiation (i.e., CUP; current clinical practice).
• Cenobamate final target daily dose prescribed (i.e., 200 mg; >200 mg).
• Number of ASMs concomitant with cenobamate (i.e., ≤2 ASMs; >2 ASMs).

Seizure frequency during the baseline and post-baseline assessments was calculated by summing the total number of seizures (all types of seizures) reported in each considered period and dividing by the duration of that period (number of days), excluding days with no available diary data, and multiplying by 28 to normalize to a monthly rate ("monthly seizure frequency").

Population will be stratified according to the following:

• Age class of patient at the time of cenobamate treatment initiation (i.e., <65 years; ≥65 years).
• Setting of cenobamate treatment initiation (i.e., CUP; current clinical practice).
• Cenobamate final target daily dose prescribed (i.e., 200 mg; >200 mg).
• Number of ASMs concomitant with cenobamate (i.e., ≤2 ASMs; >2 ASMs).

Intra-patient percent change from baseline will be defined as [(monthly seizure frequency at post-baseline assessments - monthly seizure frequency at baseline), divided by the monthly seizure frequency at baseline] multiplied by 100.

Population will be stratified according to the following:

• Age class of patient at the time of cenobamate treatment initiation (i.e., <65 years; ≥65 years).
• Setting of cenobamate treatment initiation (i.e., CUP; current clinical practice).
• Cenobamate final target daily dose prescribed (i.e., 200 mg; >200 mg).
• Number of ASMs concomitant with cenobamate (i.e., ≤2 ASMs; >2 ASMs).

Sustained seizure frequency reduction will be defined as a ≥50%/≥75%/≥90%/=100% reduction in baseline seizure frequency achieved at 12 weeks of cenobamate treatment initiation, that continues (is sustained) without interruption and without cenobamate permanent discontinuation through the observation period until 24 and 52 weeks of cenobamate treatment initiation, respectively.

Seizure frequency reduction will be defined as a ≥75%/≥90%/=100% reduction in baseline seizure frequency achieved at 12, 24 and 52 weeks of cenobamate treatment initiation, respectively.

Sustained seizure frequency reduction will be defined as a ≥50%/≥75%/≥90%/=100% reduction in baseline seizure frequency achieved at 12 weeks of cenobamate treatment initiation, that continues (is sustained) without interruption and without cenobamate permanent discontinuation through the observation period until 24 and 52 weeks of cenobamate treatment initiation, respectively

Seizure frequency reduction will be defined as a ≥75%/≥90%/=100% reduction in baseline seizure frequency achieved at 12, 24 and 52 weeks of cenobamate treatment initiation.

Absolute frequency of patients treated with cenobamate who experienced at least one AE during the applicable observation period

Relative frequency of patients treated with cenobamate who experienced at least one AE during the applicable observation period

Absolute frequency of patients treated with cenobamate who experienced at least one ADR during the applicable observation period

Relative frequency of patients treated with cenobamate who experienced at least one ADR during the applicable observation period

Absolute frequency of patients treated with at least one SAE during the applicable observation period

Relative frequency of patients treated with at least one SAE during the applicable observation period

The Health-Related Quality of life (HRQoL) of patients will be assessed by means of the 31-item Quality Of Life In Epilepsy inventory (QOLIE-31).

The 31-item Quality Of Life In Epilepsy inventory (QOLIE-31) is a patient self-reported instrument that contains 31 items grouped in seven multi-item scales ( "seizure worry", "overall QoL", "emotional well-being", "energy fatigue", "cognitive functioning", "medication effects" and "social functioning"). Different items in the QOLIE-31 have different ranges of precoded numeric values, so the scoring procedure requires conversion from raw, precoded numeric values to scores of 0-100 points, with higher scores reflecting better quality of life. The QOLIE-31 overall score is calculated by summing the product of each scale score times its weight and summing over all scales, according to the instructions obtained from copyright holders.

The patient global functioning will be assessed by means of the Clinical Global Impression (CGI) Scales. The Early Clinical Drug Evaluation Program (ECDEU) version of the CGI is a 3-item clinician rated scale that measures illness severity (CGI-S), global improvement or change (CGI-I) and treatment response (efficacy index: CGI-E).

The CGI-S score ranges from 1 (normal) through to 7 (amongst the most severely ill patients).

The calculation of the scores will be performed according to the instructions obtained from copyright holders.

The patient global functioning will be assessed by means of the Clinical Global Impression (CGI) Scales. The Early Clinical Drug Evaluation Program (ECDEU) version of the CGI is a 3-item clinician rated scale that measures illness severity (CGI-S), global improvement or change (CGI-I) and treatment response (efficacy index: CGI-E).

The CGI-I score ranges from 1 (very much improved) through to 7 (very much worse).

The calculation of the scores will be performed according to the instructions obtained from copyright holders.

The patient global functioning will be assessed by means of the Clinical Global Impression (CGI) Scales. The Early Clinical Drug Evaluation Program (ECDEU) version of the CGI is a 3-item clinician rated scale that measures illness severity (CGI-S), global improvement or change (CGI-I) and treatment response (efficacy index: CGI-E).

The CGI-E score should take account of both therapeutic effect and tolerance, and ranges from 0 (marked improvement and no toxicity) and 4 (unchanged or worse and toxicity outweigh the therapeutic effects). Each component of the CGI is rated separately; the instrument does not yield a global score.

The calculation of the scores will be performed according to the instructions obtained from copyright holders.

Daytime Sleepiness will be assessed by means of the Epworth Sleepiness Scale (ESS). The ESS is a self-administered questionnaire with 8 questions. Respondents are asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different daily activities. The ESS score can range from 0 to 24. The higher the ESS score, the higher that person Average Sleep Propensity in Daily Life (ASP), or their daytime sleepiness across a wide range of activities in their daily lives.

Anxiety and depression symptoms will be assessed by means of the the Hospital Anxiety and Depression Scale (HADS). This is a patient self-reported instrument consisting of 14 items that provide scores on two specific subscales: "Anxiety" subscale (HADS-A, 7 items) and "Depression" subscale (HADS-D, 7 items).

All items were scored on a 4-point Likert scale from 0 ("never") to 3 ("almost every day") referring to overt symptoms within the last week. Total scores range from 0 to 21 points for each subscale, with higher scores indicating higher levels of symptoms.

Retention with cenobamate will be assessed by calculating the frequency of patients still on treatment with cenobamate at 52 weeks of treatment initiation.