Epilepsy
Conditions
Keywords
Levetiracetam, Keppra® Oral Solution, Keppra® in Children
Brief summary
The purpose of this observational study is to broaden the knowledge of the known safety and efficacy profile of Keppra® (Levetiracetam) oral solution in epileptic infants younger than 12 months when treated according to routine clinical practice. Their data will be collected until they reach the age of 13 months.
Detailed description
This non-interventional sentinel sites post-authorization safety study (PASS) aims to collect additional data on use of Keppra® (Levetiracetam) oral solution in clinical practice, and on efficacy and safety of Keppra® (Levetiracetam) in infants younger than12 months. Epileptic patients between the age of 1 month and 11 months inclusive can be invited for participation to the non-interventional sentinel sites PASS, after the physician has decided to initiate therapy with Keppra® (Levetiracetam) oral solution (100 mg/ml bottle) and patient has so far been treated with Keppra® (Levetiracetam) for no longer than 10 days. The patients will be followed and their data will be collected until they reach the age of 13 months.
Interventions
None listed
Sponsors
UCB Pharma
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
1 Months to 11 Months
Healthy volunteers
No
Inclusion criteria
* diagnosis of epilepsy * being treated with Keppra® Oral Solution * aged between 1 month and 11 months inclusive at study baseline
Exclusion criteria
* none
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-Emergent Adverse Events (TEAEs) From Baseline Through Safety Follow-up Visit | From Baseline through the Safety Follow-up Visit (maximum Treatment Period is 12 months plus 2-week safety follow-up) | Number of patients with any Treatment-Emergent Adverse Events (TEAEs) as reported by the patient's parent and/or caregiver or observed by the treating physician during the study (maximum Treatment Period is 12 months plus 2-week safety follow-up). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events (TEAEs) Leading to Temporary or Permanent Discontinuation of Keppra® (Levetiracetam) From Baseline Through the Last Visit | From Baseline through the last Treatment Visit (maximum 12 months) | Number of patients with any Treatment-Emergent Adverse Events (TEAEs) leading to temporary or permanent discontinuation of Keppra® (Levetiracetam) during the Treatment Period (maximum 12 months). |
| Presence of Deviation From the Normal Milestones of Psychomotor Development From Baseline to the Last Treatment Visit | From Baseline to the last Treatment Visit (maximum 12 months) | Number of patients with presence of deviation from the normal milestones of psychomotor development during the Treatment Period (maximum 12 months). The treating physician evaluated at each visit, as part of standard clinical practice, the psychomotor development of the patient. The evaluation of the patient's psychomotor development was categorized by the motor development, the social development and the language development. |
| Mean Change From Baseline in Standardized Body Weight Scores at the Safety Follow-up Visit | From Baseline to the safety follow-up visit (maximum treatment period is 12 months plus 2-week safety follow-up) | For each visit, body weight was measured and standardization for gender and age was performed based on WHO growth charts to obtain z-scores. For this outcome measure, the mean of the differences of individual body weight z-scores from Safety Follow-up Visit to Baseline was determined. |
| Mean Change From Baseline in Standardized Body Length Scores at the Safety Follow-up Visit | From Baseline to the Safety Follow-up Visit (maximum Treatment Period is 12 months plus 2-week safety follow-up) | For each visit, body length was measured and age standardization was performed based on WHO growth charts to obtain z-scores. For this outcome measure, the difference of body length z-scores from Safety Follow-up Visit to Baseline was determined and averaged across the study population. |
| Mean Change From Baseline in Standardized Head Circumference Scores at the Safety Follow-up Visit | From Baseline to the Safety Follow-up Visit (maximum Treatment Period is 12 months plus 2-week safety follow-up) | For each visit, head circumference was measured and age standardization was performed based on WHO growth charts to obtain z-scores. For this outcome measure, the difference of head circumference z-scores from Safety Follow-up Visit to Baseline was determined and averaged across the study population. |
| Incidence of Overall Serious Treatment-Emergent Adverse Events (TEAEs) From Baseline Through the Safety Follow-up | From Baseline through the Safety Follow-up Visit (maximum Treatment Period is 12 months plus 2-weeks safety follow-up) | Number of patients with any serious Treatment-Emergent Adverse Events (TEAEs) during the study (maximum Treatment Period is 12 months plus 2-week safety follow-up). |
| Number of Patients With Abnormalities Noted During Neurological Examination From Baseline to the Last Treatment Visit | From Baseline to the last Treatment Visit (maximum 12 months) | The Number of Patients With Abnormalities Noted During Neurological Examination cannot be given because abnormality frequencies were only determined for single parameters of the neurological examination and therefore a subject might have been counted several times. |
| Global Evaluation Scale of the Psychomotor Development (GES) | From Baseline to the last Treatment Visit (maximum 12 months) | Global evaluation scale of the psychomotor development (GES): physician's assessment of the change from Baseline in the psychomotor development at the last Treatment Visit (maximum timeframe is 12 months). The GES is a 7-point scale with the following options: 7=Marked improvement 6=Moderate improvement 5=Slight improvement 4=No Change 3=Slight worsening 2=Moderate worsening 1=Marked worsening As a variant of this variable, a 3-class variable was derived as follows * Marked improvement, Moderate improvement, and Slight improvement were defined as Improved. * No change was defined as Stable. * Slight worsening, Moderate worsening, and Marked worsening were defined as Worsened. |
| Global Evaluation Scale of Epilepsy Severity (GES) | From Baseline to the last Treatment Visit (maximum time frame is 12 months) | Global evaluation scale of epilepsy severity (GES): physician's assessment of the change from Baseline of the epilepsy severity at the last Treatment Visit (maximum 12 months). The GES is a 7-point scale that assesses change in the severity of the patient's illness. The GES is a 7-point scale with the following options: 7=Marked improvement 6=Moderate improvement 5=Slight improvement 4=No Change 3=Slight worsening 2=Moderate worsening 1=Marked worsening As a variant of this variable, a 3-class variable was derived as follows * Marked improvement, Moderate improvement, and Slight improvement were defined as Improved. * No change was defined as Stable. * Slight worsening, Moderate worsening, and Marked worsening were defined as Worsened. |
| Number of Patients Who Withdraw Due to Lack or Loss of Efficacy During the Treatment Period | From Baseline through the last Treatment Visit (maximum 12 months) | Number of patients who withdraw due to lack or loss of efficacy during the Treatment Period (maximum 12 months). |
| Number of Patients With Abnormalities Noted During Physical Examination From Baseline to the Last Treatment Visit | From Baseline to the last Treatment Visit (maximum 12 months) | Number of patients with abnormalities noted during physical examination over the Treatment Period (maximum 12 months). Any abnormal findings during the physical examination during the study were reported as Adverse Events (AEs). The Number of Patients With Abnormalities Noted During Physical Examination From Baseline to the Last Treatment Visit cannot be given because abnormalities at Screening are listed only and worsening after Screening were handled as AEs and tabulated along with the other AEs. |
Countries
France, Germany, Greece, Italy, Poland, Spain, United Kingdom
Participant flow
Recruitment details
It was planned to enroll 100 patients at approximately 30-40 sites in the European Union.
Pre-assignment details
Overall 101 patients were enrolled. The Participant Flow refers to the Enrolled Set (ES). The ES consisted of patients with a signed Data Consent Form.
Participants by arm
| Arm | Count |
|---|---|
| Patients, 1 - 11 Months Old, Prescribed Keppra® Oral Solution Epileptic patients who have been prescribed Keppra® (Levetiracetam) oral solution and who were between 1 and 11 months old. The patients were followed as per current clinical practices for their condition. The choice of medical treatment, including the concomitant use of other antiepileptic drugs, was made independently by the physician in the regular course of practice and was not influenced by the study protocol. | 101 |
| Total | 101 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 7 |
| Overall Study | Disease Remission | 1 |
| Overall Study | Lack of Efficacy | 12 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Patient could not take glucose | 1 |
| Overall Study | Patient refused to swallow | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Patients, 1 - 11 Months Old, Prescribed Keppra® Oral Solution |
|---|---|
| Age, Continuous | 6.0 months STANDARD_DEVIATION 3 |
| Age, Customized >11 months | 0 participants |
| Age, Customized ≥1 - ≤6 months | 53 participants |
| Age, Customized <1 month | 2 participants |
| Age, Customized ≥6 - ≤11 months | 46 participants |
| Height | 64.16 centimeter STANDARD_DEVIATION 8.04 |
| Sex: Female, Male Female | 51 Participants |
| Sex: Female, Male Male | 50 Participants |
| Weight | 7.00 kilogram STANDARD_DEVIATION 1.94 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 19 / 101 |
| serious Total, serious adverse events | 32 / 101 |
Outcome results
Primary
Treatment-Emergent Adverse Events (TEAEs) From Baseline Through Safety Follow-up Visit
Number of patients with any Treatment-Emergent Adverse Events (TEAEs) as reported by the patient's parent and/or caregiver or observed by the treating physician during the study (maximum Treatment Period is 12 months plus 2-week safety follow-up).
Time frame: From Baseline through the Safety Follow-up Visit (maximum Treatment Period is 12 months plus 2-week safety follow-up)
Population: The Analysis Population refers to the Safety Set (SS). The SS consisted of all patients in the Enrolled Set who received at least 1 (partial) dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patients, 1 - 11 Months Old, Prescribed Keppra® Oral Solution | Treatment-Emergent Adverse Events (TEAEs) From Baseline Through Safety Follow-up Visit | 55 participants |
Secondary
Global Evaluation Scale of Epilepsy Severity (GES)
Global evaluation scale of epilepsy severity (GES): physician's assessment of the change from Baseline of the epilepsy severity at the last Treatment Visit (maximum 12 months). The GES is a 7-point scale that assesses change in the severity of the patient's illness. The GES is a 7-point scale with the following options: 7=Marked improvement 6=Moderate improvement 5=Slight improvement 4=No Change 3=Slight worsening 2=Moderate worsening 1=Marked worsening As a variant of this variable, a 3-class variable was derived as follows * Marked improvement, Moderate improvement, and Slight improvement were defined as Improved. * No change was defined as Stable. * Slight worsening, Moderate worsening, and Marked worsening were defined as Worsened.
Time frame: From Baseline to the last Treatment Visit (maximum time frame is 12 months)
Population: The Analysis Population refers to the Full Analysis Set (FAS). The FAS consisted of all patients in the Enrolled Set who had at least 1 post-Baseline efficacy assessment. Presented is the number of subjects with a non-missing measurement at Visit 7.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Patients, 1 - 11 Months Old, Prescribed Keppra® Oral Solution | Global Evaluation Scale of Epilepsy Severity (GES) | Improved | 61 participants |
| Patients, 1 - 11 Months Old, Prescribed Keppra® Oral Solution | Global Evaluation Scale of Epilepsy Severity (GES) | Stable | 16 participants |
| Patients, 1 - 11 Months Old, Prescribed Keppra® Oral Solution | Global Evaluation Scale of Epilepsy Severity (GES) | Worsened | 8 participants |
Secondary
Global Evaluation Scale of the Psychomotor Development (GES)
Global evaluation scale of the psychomotor development (GES): physician's assessment of the change from Baseline in the psychomotor development at the last Treatment Visit (maximum timeframe is 12 months). The GES is a 7-point scale with the following options: 7=Marked improvement 6=Moderate improvement 5=Slight improvement 4=No Change 3=Slight worsening 2=Moderate worsening 1=Marked worsening As a variant of this variable, a 3-class variable was derived as follows * Marked improvement, Moderate improvement, and Slight improvement were defined as Improved. * No change was defined as Stable. * Slight worsening, Moderate worsening, and Marked worsening were defined as Worsened.
Time frame: From Baseline to the last Treatment Visit (maximum 12 months)
Population: The Analysis Population refers to the Full Analysis Set (FAS). The FAS consisted of all patients in the Enrolled Set who had at least 1 post-Baseline efficacy assessment. Presented is the number of subjects with a non-missing measurement at Visit 7.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Patients, 1 - 11 Months Old, Prescribed Keppra® Oral Solution | Global Evaluation Scale of the Psychomotor Development (GES) | Improved | 45 participants |
| Patients, 1 - 11 Months Old, Prescribed Keppra® Oral Solution | Global Evaluation Scale of the Psychomotor Development (GES) | Stable | 31 participants |
| Patients, 1 - 11 Months Old, Prescribed Keppra® Oral Solution | Global Evaluation Scale of the Psychomotor Development (GES) | Worsened | 9 participants |
Secondary
Incidence of Overall Serious Treatment-Emergent Adverse Events (TEAEs) From Baseline Through the Safety Follow-up
Number of patients with any serious Treatment-Emergent Adverse Events (TEAEs) during the study (maximum Treatment Period is 12 months plus 2-week safety follow-up).
Time frame: From Baseline through the Safety Follow-up Visit (maximum Treatment Period is 12 months plus 2-weeks safety follow-up)
Population: The Analysis Population refers to the Safety Set (SS). The SS consisted of all patients in the Enrolled Set who received at least 1 (partial) dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patients, 1 - 11 Months Old, Prescribed Keppra® Oral Solution | Incidence of Overall Serious Treatment-Emergent Adverse Events (TEAEs) From Baseline Through the Safety Follow-up | 32 participants |
Secondary
Incidence of Treatment-Emergent Adverse Events (TEAEs) Leading to Temporary or Permanent Discontinuation of Keppra® (Levetiracetam) From Baseline Through the Last Visit
Number of patients with any Treatment-Emergent Adverse Events (TEAEs) leading to temporary or permanent discontinuation of Keppra® (Levetiracetam) during the Treatment Period (maximum 12 months).
Time frame: From Baseline through the last Treatment Visit (maximum 12 months)
Population: The Analysis Population refers to the Safety Set (SS). The SS consisted of all patients in the Enrolled Set who received at least 1 (partial) dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patients, 1 - 11 Months Old, Prescribed Keppra® Oral Solution | Incidence of Treatment-Emergent Adverse Events (TEAEs) Leading to Temporary or Permanent Discontinuation of Keppra® (Levetiracetam) From Baseline Through the Last Visit | 5 participants |
Secondary
Mean Change From Baseline in Standardized Body Length Scores at the Safety Follow-up Visit
For each visit, body length was measured and age standardization was performed based on WHO growth charts to obtain z-scores. For this outcome measure, the difference of body length z-scores from Safety Follow-up Visit to Baseline was determined and averaged across the study population.
Time frame: From Baseline to the Safety Follow-up Visit (maximum Treatment Period is 12 months plus 2-week safety follow-up)
Population: The Analysis Population refers to the Safety Set (SS). The SS consisted of all patients in the Enrolled Set who received at least 1 (partial) dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients, 1 - 11 Months Old, Prescribed Keppra® Oral Solution | Mean Change From Baseline in Standardized Body Length Scores at the Safety Follow-up Visit | 0.335 z-scores | Standard Deviation 2.058 |
Secondary
Mean Change From Baseline in Standardized Body Weight Scores at the Safety Follow-up Visit
For each visit, body weight was measured and standardization for gender and age was performed based on WHO growth charts to obtain z-scores. For this outcome measure, the mean of the differences of individual body weight z-scores from Safety Follow-up Visit to Baseline was determined.
Time frame: From Baseline to the safety follow-up visit (maximum treatment period is 12 months plus 2-week safety follow-up)
Population: The Analysis Population refers to the Safety Set (SS). The SS consisted of all patients in the Enrolled Set who received at least 1 (partial) dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients, 1 - 11 Months Old, Prescribed Keppra® Oral Solution | Mean Change From Baseline in Standardized Body Weight Scores at the Safety Follow-up Visit | 0.740 z-scores | Standard Deviation 1.304 |
Secondary
Mean Change From Baseline in Standardized Head Circumference Scores at the Safety Follow-up Visit
For each visit, head circumference was measured and age standardization was performed based on WHO growth charts to obtain z-scores. For this outcome measure, the difference of head circumference z-scores from Safety Follow-up Visit to Baseline was determined and averaged across the study population.
Time frame: From Baseline to the Safety Follow-up Visit (maximum Treatment Period is 12 months plus 2-week safety follow-up)
Population: The Analysis Population refers to the Safety Set (SS). The SS consisted of all patients in the Enrolled Set who received at least 1 (partial) dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients, 1 - 11 Months Old, Prescribed Keppra® Oral Solution | Mean Change From Baseline in Standardized Head Circumference Scores at the Safety Follow-up Visit | -0.307 z-scores | Standard Deviation 1.802 |
Secondary
Number of Patients Who Withdraw Due to Lack or Loss of Efficacy During the Treatment Period
Number of patients who withdraw due to lack or loss of efficacy during the Treatment Period (maximum 12 months).
Time frame: From Baseline through the last Treatment Visit (maximum 12 months)
Population: The Analysis Population refers to the Full Analysis Set (FAS). The FAS consisted of all patients in the Enrolled Set who had at least 1 post-Baseline efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patients, 1 - 11 Months Old, Prescribed Keppra® Oral Solution | Number of Patients Who Withdraw Due to Lack or Loss of Efficacy During the Treatment Period | 12 participants |
Secondary
Number of Patients With Abnormalities Noted During Neurological Examination From Baseline to the Last Treatment Visit
The Number of Patients With Abnormalities Noted During Neurological Examination cannot be given because abnormality frequencies were only determined for single parameters of the neurological examination and therefore a subject might have been counted several times.
Time frame: From Baseline to the last Treatment Visit (maximum 12 months)
Secondary
Number of Patients With Abnormalities Noted During Physical Examination From Baseline to the Last Treatment Visit
Number of patients with abnormalities noted during physical examination over the Treatment Period (maximum 12 months). Any abnormal findings during the physical examination during the study were reported as Adverse Events (AEs). The Number of Patients With Abnormalities Noted During Physical Examination From Baseline to the Last Treatment Visit cannot be given because abnormalities at Screening are listed only and worsening after Screening were handled as AEs and tabulated along with the other AEs.
Time frame: From Baseline to the last Treatment Visit (maximum 12 months)
Secondary
Presence of Deviation From the Normal Milestones of Psychomotor Development From Baseline to the Last Treatment Visit
Number of patients with presence of deviation from the normal milestones of psychomotor development during the Treatment Period (maximum 12 months). The treating physician evaluated at each visit, as part of standard clinical practice, the psychomotor development of the patient. The evaluation of the patient's psychomotor development was categorized by the motor development, the social development and the language development.
Time frame: From Baseline to the last Treatment Visit (maximum 12 months)
Population: The Analysis Population refers to the Safety Set (SS). The SS consisted of all patients in the Enrolled Set who received at least 1 (partial) dose of study medication. Presented is the number of subjects with non-missing data on psychomotor development at the corresponding visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Patients, 1 - 11 Months Old, Prescribed Keppra® Oral Solution | Presence of Deviation From the Normal Milestones of Psychomotor Development From Baseline to the Last Treatment Visit | Any deviation | 54 participants |
| Patients, 1 - 11 Months Old, Prescribed Keppra® Oral Solution | Presence of Deviation From the Normal Milestones of Psychomotor Development From Baseline to the Last Treatment Visit | Motor development | 52 participants |
| Patients, 1 - 11 Months Old, Prescribed Keppra® Oral Solution | Presence of Deviation From the Normal Milestones of Psychomotor Development From Baseline to the Last Treatment Visit | Social development | 48 participants |
| Patients, 1 - 11 Months Old, Prescribed Keppra® Oral Solution | Presence of Deviation From the Normal Milestones of Psychomotor Development From Baseline to the Last Treatment Visit | Language development | 48 participants |