Focal Epilepsy
Conditions
Keywords
epilepsy antiepileptic biotherapy
Brief summary
Assessment of the efficacy under daily clinical conditions of the new antiepileptic drugs (AEDs) gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine and topiramate, used as first-choice combination therapy (bitherapy) in patients with focal epilepsy.
Interventions
DRUGGabapentin, Lamotrigine, Levetiracetam, Pregabalin, Oxcarbacepine, Tiagabine, Topiramate, Zonisamide
* Gabapentin: up to 3.600 mg/d * Lamotrigine: up to 400 mg/d * Levetiracetam: up to 3.000 mg/d * Pregabalin: up to 600 mg/d * Oxcarbazepine: up to 2.400 mg/d * Tiagabine: up to 30 mg/d * Topiramate: up to 400 mg/d * Zonisamide: up to 500 mg/d
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Aged 18 years or older. * Diagnosis of focal epilepsy. * Previous failure of one or more AEDs used in monotherapy. * Background treatment with an antiepileptic drug. * The investigator has considered that the patient must start treatment with some of the seven new AEDs in combination therapy: lamotrigine, levetiracetam, gabapentin, oxcarbazepine, pregabalin, tiagabine and/or topiramate. * History of seizures in the patient in the past 3 months. * The patient or legal guardian must be able to understand the characteristics of the study and fill in the seizure diaries. * Written informed consent.
Exclusion criteria
* Inability to comply with the study requirements. * Diagnosis of generalized epilepsy or inability to establish if focal or generalized. * Presence of serious or uncontrolled systemic disease, serious psychiatric disease or progressive neurological disease. * History of alcoholism, drug addiction, or abuse of medicines in the past two years. * Psychogenic seizures in the two years prior to inclusion in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants Classified as Responders | Baseline, Month 3, Month 6 (last 3 months of treatment) | Responder = decrease in number of seizures by \>=50 percent (%) during the last 3 months of treatment before discontinuation (assessed at Month 3 and Month 6) versus the number of seizures that occurred during the 3 months before the baseline visit (baseline). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Seizure-free Participants During the Last 3 Months Before Discontinuation | Baseline, Month 3, Month 6 (last 3 months of treatment) | — |
| Percent Change From Baseline in the Median Number of Seizures During the Last 3 Months of Treatment | Baseline, Month 3, Month 6 (last 3 months of treatment) | — |
| Percent of Days Without Crisis During the Study | Baseline through Month 6 (or end of treatment) | Crisis was defined as the total number of seizures during the study, the seizures at month 3 plus the seizures at month 6. The percent of days without crisis is number of days of study (date of last visit minus date of baseline visit) without crisis divided by number of days of study, multiplied by 100. |
| Time to First Seizure | Baseline to Month 6 (or end of treatment) | Number of days to first seizure after baseline. |
| Percent of Participants Who Continued on Study Medication to Month 6 | Baseline to Month 6 | Retention rate: percent of participants who continued on study medication throughout the 6 Month period after inclusion in the study. |
| Time to Discontinuation Due to Lack of Efficacy | Baseline, Month 3, Month 6 | — |
| Time to Discontinuation Due to Safety, Tolerability, or Treatment Compliance | Baseline, Month 3, Month 6 | — |
| Time to Discontinuation Due to Other Reasons | Baseline, Month 3, Month 6 | — |
| Treatment Satisfaction Evaluated by Patient Global Impression of Change Visual Analog Scale (VAS) | Baseline, Month 3, Month 6 | Patient Global Impression of Change VAS: subject rated instrument to measure subject's change in overall status; range from 0 (much better) to 10 (much worse). |
| Percent of Participants Reaching Monotherapy | Baseline through Month 6 (or end of study) | Percent of participants who started on more than one treatment (bitherapy) and reached monotherapy by end of study. |
| Percent of Participants With Reduction in Number of Seizures >=25% and >=75% During the Last 3 Months of Treatment | Baseline, Month 3, Month 6 (last 3 months of treatment) | Percent of participants with reduction in number of seizures \>=25% and \>=75% during the last 3 months of treatment before discontinuation (assessed at Month 3 and Month 6) versus the 3 month period before the baseline visit. |
| Percent of Participants That Reduced, Maintained and Increased the Doses of the Initial Treatment Administered in Monotherapy | Baseline through Month 6 (or end of treatment) | — |
| Change From Baseline to Month 6 in the Hospital Anxiety and Depression Scale (HADS) | Baseline to Month 6 | HADS: subject rated questionnaire with 2 subscales. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms. |
| Change From Baseline to Month 6 in Quality of Life 10 Domains (QOLIE-10) | Baseline to Month 6 | QOLIE-10: 10-item questionnaire evaluates health-related quality of life in individuals with epliepsy. Comprised of 7 components: seizure worry, overall quality of life, emotional well-being, energy, cognitive functioning, medication effects (physical and mental effects), and social function (work, driving, social function). Total score rated 0 to 100; higher score = higher quality of life. |
| Change From Baseline to Months 3 and 6 in Health Condition: Euro Quality of Life Scale (EQ-5D) Visual Analog Scale (VAS) | Baseline, Month 3, Month 6 | Assessment of the health condition of the subjects using the EQ-5D VAS: subject rated questionnaire to assess health-related quality of life in terms of a single index value. Using the VAS subjects rated current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state. |
| Change in Sleep Disturbances From Baseline to Month 6: Medical Outcomes Study Sleep Scale (MOS-SS) | Baseline to Month 6 | Subject rated instrument to assess key constructs of sleep; assesses sleep quality and quantity. Consists of a 6-item and 9-item overall sleep problems index measuring time to fall asleep and sleep duration in past 4 weeks; 5 subscales rated 1 (all the time) to 6 (none of the time): sleep disturbance, snoring, awaken short of breath, somnolence, and adequacy. Transformed scores range = 0 to 100; higher score indicates greater intensity of attribute. Two additional subscales = sleep quantity (range 0-24 hours) and optimal sleep (number of participants with optimal sleep 7-8 hours per night). |
| Percent of Participants Indicating Optimal Sleep on the Optimal Sleep Subscale: Medical Outcomes Study Sleep Scale (MOS-SS) | Baseline, Month 6 | MOS-SS: subject rated instrument used to assess the key constructs of sleep; assesses sleep quantity and quality and is comprised of 12 items yielding 7 subscale scores and 2 composite index scores. Optimal sleep subscale is derived from sleep quantity average hours of sleep over the past 4 weeks; percent of participants with response YES (optimal) if sleep quantilty was 7-8 hours of sleep per night. |
| Change From Baseline to Month 6 in Visits to a Specialist or the Emergency Room Because of Epilepsy | Baseline to Month 6 | Numerical assessment of change in the number of visits to a specialist or the emergency room because of epilepsy needed during the study. |
| Change From Baseline to Month 6 in Total Number of Days Hospitalized Because of Epilepsy | Baseline to Month 6 | Numerical assessment of change in total number of days hospitalized because of epilepsy during the study. |
| Percent of Participants With Cessation of Occupation, Requirement of Caregiver, or Admission to Intensive Care Unit | Month 6 | Percent of participants with cessation of usual occupation, requirement of an informal caregiver, and who required admission to the intensive care unit (ICU). |
| Percent of Participants That Reduced, Maintained and Increased Their Doses of New Antiepileptic Drugs (AED) | Baseline to Month 6 (or end of treatment) | — |
Participant flow
Pre-assignment details
Given the observational nature of the study, the selection of treatment and dose of study medication was independent from participation in the study and was determined by daily clinical practice.
Participants by arm
| Arm | Count |
|---|---|
| All Antiepileptic Drugs Pregabalin, Levetiracetam, Topiramate, Lamotrigine, Oxcarbazepine, Zonisamide, Gabapentin: treatment, dose and frequency of administration determined by daily clinical practice | 111 |
| Total | 111 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 1 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Subject Defaulted | 1 |
Baseline characteristics
| Characteristic | All Antiepileptic Drugs |
|---|---|
| Age, Continuous | 45.3 years STANDARD_DEVIATION 16.1 |
| Sex: Female, Male Female | 52 Participants |
| Sex: Female, Male Male | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 111 | 5 / 40 |
| serious Total, serious adverse events | 0 / 111 | 0 / 40 |
Outcome results
Primary
Percent of Participants Classified as Responders
Responder = decrease in number of seizures by \>=50 percent (%) during the last 3 months of treatment before discontinuation (assessed at Month 3 and Month 6) versus the number of seizures that occurred during the 3 months before the baseline visit (baseline).
Time frame: Baseline, Month 3, Month 6 (last 3 months of treatment)
Population: Full Analysis Set (FAS): intent-to-treat population = those who took at least 1 dose of study medication and had post-baseline data for at least 1 efficacy endpoint. Last Observation Carried Forward (LOCF) captures last 3 months of treatment for subjects who discontinued between Month 3 and Month 6 only. N=number of subjects with evaluable data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Antiepileptic Drugs | Percent of Participants Classified as Responders | Month 3 | 76.7 percent of participants |
| All Antiepileptic Drugs | Percent of Participants Classified as Responders | Month 6 | 80.0 percent of participants |
Comparison: Month 3: p-value versus baseline.p-value: <0.0001McNemar
Comparison: Month 6: p-value versus baseline.p-value: <0.0001McNemar
Secondary
Change From Baseline to Month 6 in Quality of Life 10 Domains (QOLIE-10)
QOLIE-10: 10-item questionnaire evaluates health-related quality of life in individuals with epliepsy. Comprised of 7 components: seizure worry, overall quality of life, emotional well-being, energy, cognitive functioning, medication effects (physical and mental effects), and social function (work, driving, social function). Total score rated 0 to 100; higher score = higher quality of life.
Time frame: Baseline to Month 6
Population: FAS; LOCF. N=number of subjects with evaluable data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Antiepileptic Drugs | Change From Baseline to Month 6 in Quality of Life 10 Domains (QOLIE-10) | Emotions (mood) | 0.7 scores on scale | Standard Deviation 16 |
| All Antiepileptic Drugs | Change From Baseline to Month 6 in Quality of Life 10 Domains (QOLIE-10) | Energy | 0.4 scores on scale | Standard Deviation 17.8 |
| All Antiepileptic Drugs | Change From Baseline to Month 6 in Quality of Life 10 Domains (QOLIE-10) | Daily activities | 0.6 scores on scale | Standard Deviation 12.9 |
| All Antiepileptic Drugs | Change From Baseline to Month 6 in Quality of Life 10 Domains (QOLIE-10) | Mental function | 1.2 scores on scale | Standard Deviation 20.8 |
| All Antiepileptic Drugs | Change From Baseline to Month 6 in Quality of Life 10 Domains (QOLIE-10) | Medication effects (physical/ mental) | -1.1 scores on scale | Standard Deviation 14.9 |
| All Antiepileptic Drugs | Change From Baseline to Month 6 in Quality of Life 10 Domains (QOLIE-10) | Worry about seizures (impact of seizures) | 9.0 scores on scale | Standard Deviation 21.1 |
| All Antiepileptic Drugs | Change From Baseline to Month 6 in Quality of Life 10 Domains (QOLIE-10) | Overall quality of life | 3.8 scores on scale | Standard Deviation 17.2 |
Comparison: Energy: p-value versus baseline.p-value: 0.8284t-test, 2 sided
Comparison: Emotions (mood): p-value versus baseline.p-value: 0.6299t-test, 2 sided
Comparison: Daily activities: p-value versus baseline.p-value: 0.6162t-test, 2 sided
Comparison: Mental function: p-value versus baseline.p-value: 0.5609t-test, 2 sided
Comparison: Medication effects (physical/ mental): p-value versus baseline.p-value: 0.4635t-test, 2 sided
Comparison: Worry about seizures (impact of seizures): p-value versus baseline.p-value: <0.0001t-test, 2 sided
Comparison: Overall quality of life: p-value versus baseline.p-value: 0.0258t-test, 2 sided
Secondary
Change From Baseline to Month 6 in the Hospital Anxiety and Depression Scale (HADS)
HADS: subject rated questionnaire with 2 subscales. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms.
Time frame: Baseline to Month 6
Population: FAS; LOCF. N=number of subjects with evaluable data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Antiepileptic Drugs | Change From Baseline to Month 6 in the Hospital Anxiety and Depression Scale (HADS) | Depression | -0.5 scores on scale | Standard Deviation 3.5 |
| All Antiepileptic Drugs | Change From Baseline to Month 6 in the Hospital Anxiety and Depression Scale (HADS) | Anxiety | -0.6 scores on scale | Standard Deviation 3 |
Comparison: Depression domain: P-value vs baseline.p-value: 0.1797t-test, 2 sided
Comparison: Anxiety domain: P-value vs baseline.p-value: 0.0433t-test, 2 sided
Secondary
Change From Baseline to Month 6 in Total Number of Days Hospitalized Because of Epilepsy
Numerical assessment of change in total number of days hospitalized because of epilepsy during the study.
Time frame: Baseline to Month 6
Population: FAS; LOCF. N=number of subjects with evaluable data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Antiepileptic Drugs | Change From Baseline to Month 6 in Total Number of Days Hospitalized Because of Epilepsy | -8.0 Days | Standard Deviation 68.6 |
Comparison: P-value versus baseline.p-value: 0.3141t-test, 2 sided
Secondary
Change From Baseline to Month 6 in Visits to a Specialist or the Emergency Room Because of Epilepsy
Numerical assessment of change in the number of visits to a specialist or the emergency room because of epilepsy needed during the study.
Time frame: Baseline to Month 6
Population: FAS; LOCF. Costs involved in health and non-health resources needed during the study were not analyzed as planned with this endpoint. N=number of subjects with visits to a specialist because of epilepsy.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Antiepileptic Drugs | Change From Baseline to Month 6 in Visits to a Specialist or the Emergency Room Because of Epilepsy | Number of visits to a specialist (n=94) | -0.6 visits | Standard Deviation 2.3 |
| All Antiepileptic Drugs | Change From Baseline to Month 6 in Visits to a Specialist or the Emergency Room Because of Epilepsy | Number of visits to the emergency room (n=79) | -0.3 visits | Standard Deviation 0.9 |
Comparison: Number of visits to a specialist because of epilepsy: p-value versus baseline.p-value: 0.0226t-test, 2 sided
Comparison: Number of visits to the emergency room because of epilepsy: p-value versus baseline.p-value: 0.0017t-test, 2 sided
Secondary
Change From Baseline to Months 3 and 6 in Health Condition: Euro Quality of Life Scale (EQ-5D) Visual Analog Scale (VAS)
Assessment of the health condition of the subjects using the EQ-5D VAS: subject rated questionnaire to assess health-related quality of life in terms of a single index value. Using the VAS subjects rated current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state.
Time frame: Baseline, Month 3, Month 6
Population: FAS LOCF. N=number of subjects with evaluable data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Antiepileptic Drugs | Change From Baseline to Months 3 and 6 in Health Condition: Euro Quality of Life Scale (EQ-5D) Visual Analog Scale (VAS) | Month 3 | -0.4 scores on scale | Standard Deviation 16.2 |
| All Antiepileptic Drugs | Change From Baseline to Months 3 and 6 in Health Condition: Euro Quality of Life Scale (EQ-5D) Visual Analog Scale (VAS) | Month 6 | 1.2 scores on scale | Standard Deviation 15.6 |
Comparison: Month 3: p-value versus baseline.p-value: 0.7822t-test, 2 sided
Comparison: Month 6: p-value versus baseline.p-value: 0.4471t-test, 2 sided
Secondary
Change in Sleep Disturbances From Baseline to Month 6: Medical Outcomes Study Sleep Scale (MOS-SS)
Subject rated instrument to assess key constructs of sleep; assesses sleep quality and quantity. Consists of a 6-item and 9-item overall sleep problems index measuring time to fall asleep and sleep duration in past 4 weeks; 5 subscales rated 1 (all the time) to 6 (none of the time): sleep disturbance, snoring, awaken short of breath, somnolence, and adequacy. Transformed scores range = 0 to 100; higher score indicates greater intensity of attribute. Two additional subscales = sleep quantity (range 0-24 hours) and optimal sleep (number of participants with optimal sleep 7-8 hours per night).
Time frame: Baseline to Month 6
Population: FAS LOCF. Change from baseline in Optimal sleep is not shown as changes from baseline were only evaluated for continuous parameters. N=number of subjects with evaluable data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Antiepileptic Drugs | Change in Sleep Disturbances From Baseline to Month 6: Medical Outcomes Study Sleep Scale (MOS-SS) | Snoring | 0.0 scores on scale | Standard Deviation 15.6 |
| All Antiepileptic Drugs | Change in Sleep Disturbances From Baseline to Month 6: Medical Outcomes Study Sleep Scale (MOS-SS) | Sleep disturbance | -1.7 scores on scale | Standard Deviation 15.1 |
| All Antiepileptic Drugs | Change in Sleep Disturbances From Baseline to Month 6: Medical Outcomes Study Sleep Scale (MOS-SS) | Awake short of breath | 1.1 scores on scale | Standard Deviation 14.6 |
| All Antiepileptic Drugs | Change in Sleep Disturbances From Baseline to Month 6: Medical Outcomes Study Sleep Scale (MOS-SS) | Quantity | 0.2 scores on scale | Standard Deviation 0.8 |
| All Antiepileptic Drugs | Change in Sleep Disturbances From Baseline to Month 6: Medical Outcomes Study Sleep Scale (MOS-SS) | Adequacy | 2.8 scores on scale | Standard Deviation 15 |
| All Antiepileptic Drugs | Change in Sleep Disturbances From Baseline to Month 6: Medical Outcomes Study Sleep Scale (MOS-SS) | Somnolence | 0.6 scores on scale | Standard Deviation 11 |
| All Antiepileptic Drugs | Change in Sleep Disturbances From Baseline to Month 6: Medical Outcomes Study Sleep Scale (MOS-SS) | Sleep problems (summary 6) | -0.9 scores on scale | Standard Deviation 11.7 |
| All Antiepileptic Drugs | Change in Sleep Disturbances From Baseline to Month 6: Medical Outcomes Study Sleep Scale (MOS-SS) | Sleep problems (summary 9) | -0.9 scores on scale | Standard Deviation 13.2 |
Comparison: Sleep disturbance: p-value versus baseline.p-value: 0.2452t-test, 2 sided
Comparison: Snoring: p-value verus baseline.p-value: 1t-test, 2 sided
Comparison: Awake short of breath: p-value versus baseline.p-value: 0.4253t-test, 2 sided
Comparison: Quantity: p-value versus baseline.p-value: 0.0572t-test, 2 sided
Comparison: Adequacy: p-value versus baseline.p-value: 0.0625t-test, 2 sided
Comparison: Somnolence: p-value versus baseline.p-value: 0.554t-test, 2 sided
Comparison: Sleep problems (summary 6): p-value versus baseline.p-value: 0.4204t-test, 2 sided
Comparison: Sleep problems (summary 9): p-value versus baseline.p-value: 0.4869t-test, 2 sided
Secondary
Percent Change From Baseline in the Median Number of Seizures During the Last 3 Months of Treatment
Time frame: Baseline, Month 3, Month 6 (last 3 months of treatment)
Population: FAS LOCF. N=number of subjects with evaluable data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Antiepileptic Drugs | Percent Change From Baseline in the Median Number of Seizures During the Last 3 Months of Treatment | -75.0 percent change |
p-value: <0.0001Wilcoxon Signed Rank Test
Secondary
Percent of Days Without Crisis During the Study
Crisis was defined as the total number of seizures during the study, the seizures at month 3 plus the seizures at month 6. The percent of days without crisis is number of days of study (date of last visit minus date of baseline visit) without crisis divided by number of days of study, multiplied by 100.
Time frame: Baseline through Month 6 (or end of treatment)
Population: The percentage of days without crisis during the study was not evaluable because a diary with the daily number of crises was not collected.
Secondary
Percent of Participants Indicating Optimal Sleep on the Optimal Sleep Subscale: Medical Outcomes Study Sleep Scale (MOS-SS)
MOS-SS: subject rated instrument used to assess the key constructs of sleep; assesses sleep quantity and quality and is comprised of 12 items yielding 7 subscale scores and 2 composite index scores. Optimal sleep subscale is derived from sleep quantity average hours of sleep over the past 4 weeks; percent of participants with response YES (optimal) if sleep quantilty was 7-8 hours of sleep per night.
Time frame: Baseline, Month 6
Population: FAS; LOCF.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Antiepileptic Drugs | Percent of Participants Indicating Optimal Sleep on the Optimal Sleep Subscale: Medical Outcomes Study Sleep Scale (MOS-SS) | Month 6 | 65.7 percent of participants |
| All Antiepileptic Drugs | Percent of Participants Indicating Optimal Sleep on the Optimal Sleep Subscale: Medical Outcomes Study Sleep Scale (MOS-SS) | Baseline | 56.5 percent of participants |
Comparison: Month 6: p-value versus baseline.p-value: 0.0863McNemar
Secondary
Percent of Participants Reaching Monotherapy
Percent of participants who started on more than one treatment (bitherapy) and reached monotherapy by end of study.
Time frame: Baseline through Month 6 (or end of study)
Population: FAS; LOCF. N=number of participants who started on bitherapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Antiepileptic Drugs | Percent of Participants Reaching Monotherapy | 2.9 percent of partipants |
Secondary
Percent of Participants That Reduced, Maintained and Increased the Doses of the Initial Treatment Administered in Monotherapy
Time frame: Baseline through Month 6 (or end of treatment)
Population: FAS; LOCF. N= number of subjects with initial treatment administered as monotherapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Antiepileptic Drugs | Percent of Participants That Reduced, Maintained and Increased the Doses of the Initial Treatment Administered in Monotherapy | Reduced | 0.0 percent of participants |
| All Antiepileptic Drugs | Percent of Participants That Reduced, Maintained and Increased the Doses of the Initial Treatment Administered in Monotherapy | Maintained | 100.0 percent of participants |
| All Antiepileptic Drugs | Percent of Participants That Reduced, Maintained and Increased the Doses of the Initial Treatment Administered in Monotherapy | Increased | 0.0 percent of participants |
Secondary
Percent of Participants That Reduced, Maintained and Increased Their Doses of New Antiepileptic Drugs (AED)
Time frame: Baseline to Month 6 (or end of treatment)
Population: FAS; LOCF.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Antiepileptic Drugs | Percent of Participants That Reduced, Maintained and Increased Their Doses of New Antiepileptic Drugs (AED) | Reduced | 0.9 percent of participants |
| All Antiepileptic Drugs | Percent of Participants That Reduced, Maintained and Increased Their Doses of New Antiepileptic Drugs (AED) | Maintained | 68.5 percent of participants |
| All Antiepileptic Drugs | Percent of Participants That Reduced, Maintained and Increased Their Doses of New Antiepileptic Drugs (AED) | Increased | 30.6 percent of participants |
Secondary
Percent of Participants Who Continued on Study Medication to Month 6
Retention rate: percent of participants who continued on study medication throughout the 6 Month period after inclusion in the study.
Time frame: Baseline to Month 6
Population: FAS; LOCF.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Antiepileptic Drugs | Percent of Participants Who Continued on Study Medication to Month 6 | 97.1 percent of participants |
Secondary
Percent of Participants With Cessation of Occupation, Requirement of Caregiver, or Admission to Intensive Care Unit
Percent of participants with cessation of usual occupation, requirement of an informal caregiver, and who required admission to the intensive care unit (ICU).
Time frame: Month 6
Population: FAS; LOCF.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Antiepileptic Drugs | Percent of Participants With Cessation of Occupation, Requirement of Caregiver, or Admission to Intensive Care Unit | Stopped Usual Occupation | 16.2 percent of participants |
| All Antiepileptic Drugs | Percent of Participants With Cessation of Occupation, Requirement of Caregiver, or Admission to Intensive Care Unit | Required Informal Caregiver | 6.6 percent of participants |
| All Antiepileptic Drugs | Percent of Participants With Cessation of Occupation, Requirement of Caregiver, or Admission to Intensive Care Unit | Required Admission to ICU | 0.0 percent of participants |
Comparison: Cessation of usual occupation: p-value versus baseline.p-value: 0.0708t-test, 2 sided
Comparison: Requirement of informal caregiver: p-value versus baseline.p-value: 1t-test, 2 sided
Comparison: Required admission to ICU: p-value versus baseline.p-value: 1t-test, 2 sided
Secondary
Percent of Participants With Reduction in Number of Seizures >=25% and >=75% During the Last 3 Months of Treatment
Percent of participants with reduction in number of seizures \>=25% and \>=75% during the last 3 months of treatment before discontinuation (assessed at Month 3 and Month 6) versus the 3 month period before the baseline visit.
Time frame: Baseline, Month 3, Month 6 (last 3 months of treatment)
Population: FAS; LOCF. N=number of subjects with evaluable data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Antiepileptic Drugs | Percent of Participants With Reduction in Number of Seizures >=25% and >=75% During the Last 3 Months of Treatment | Month 3: >=25% | 86.7 percent of participants |
| All Antiepileptic Drugs | Percent of Participants With Reduction in Number of Seizures >=25% and >=75% During the Last 3 Months of Treatment | Month 3: >=75% | 27.8 percent of participants |
| All Antiepileptic Drugs | Percent of Participants With Reduction in Number of Seizures >=25% and >=75% During the Last 3 Months of Treatment | Month 6: >= 25% | 86.7 percent of participants |
| All Antiepileptic Drugs | Percent of Participants With Reduction in Number of Seizures >=25% and >=75% During the Last 3 Months of Treatment | Month 6: >=75% | 54.4 percent of participants |
Comparison: Month 3 \>=25% reduction: p-value versus baseline.p-value: <0.0001McNemar
Comparison: Month 3 \>=75% reduction: p-value versus baseline.p-value: <0.0001McNemar
Comparison: Month 6: \>=25% reduction: p-value versus baseline.p-value: <0.0001McNemar
Comparison: Month 6: \>=75% reduction: p-value versus baseline.p-value: <0.0001McNemar
Secondary
Percent of Seizure-free Participants During the Last 3 Months Before Discontinuation
Time frame: Baseline, Month 3, Month 6 (last 3 months of treatment)
Population: FAS; LOCF. N=number of subjects with evaluable data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Antiepileptic Drugs | Percent of Seizure-free Participants During the Last 3 Months Before Discontinuation | Month 3 | 10.0 percent of participants |
| All Antiepileptic Drugs | Percent of Seizure-free Participants During the Last 3 Months Before Discontinuation | Month 6 | 20.0 percent of participants |
Comparison: Month 3: p-value versus baseline.p-value: 0.0039McNemar
Comparison: Month 6: p-value versus baseline.p-value: <0.0001McNemar
Secondary
Time to Discontinuation Due to Lack of Efficacy
Time frame: Baseline, Month 3, Month 6
Population: FAS; LOCF. As no participants discontinued due to lack of efficacy, the time to exit analysis was not performed.
Secondary
Time to Discontinuation Due to Other Reasons
Time frame: Baseline, Month 3, Month 6
Population: FAS; LOCF. Due to the low number of participants who discontinued due to other reasons, the time to exit analyses was not performed.
Secondary
Time to Discontinuation Due to Safety, Tolerability, or Treatment Compliance
Time frame: Baseline, Month 3, Month 6
Population: FAS; LOCF. Due to the low number of participants who discontinued due to safety, tolerability or compliance with treatment, the time to exit analysis was not performed.
Secondary
Time to First Seizure
Number of days to first seizure after baseline.
Time frame: Baseline to Month 6 (or end of treatment)
Population: FAS LOCF. N=number of subjects with evaluable data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Antiepileptic Drugs | Time to First Seizure | 35.9 days | Standard Deviation 40.2 |
Secondary
Treatment Satisfaction Evaluated by Patient Global Impression of Change Visual Analog Scale (VAS)
Patient Global Impression of Change VAS: subject rated instrument to measure subject's change in overall status; range from 0 (much better) to 10 (much worse).
Time frame: Baseline, Month 3, Month 6
Population: FAS; LOCF. The scale for this endpoint was not collected and results were not analyzed as planned.