Epilepsy
Conditions
Keywords
Epilepsy, Topiramate, Levetiracetam, Pediatric
Brief summary
The purpose of this study is to evaluate the safety of topiramate monotherapy compared with levetiracetam another standard antiepileptic drug (AED), as monotherapy for new-onset or recent-onset epilepsy (seizure disorder) on pediatric growth and maturation, bone mineralization, and kidney stone formation in children aged 2 to 15 years.
Detailed description
This is a randomized (study medication assigned to participants by chance), open-label, multi-centric (conducted in more than one center) and 2-arm flexible-dose monotherapy study of topiramate compared with 1 another AED (levetiracetam) in pediatric participants with epilepsy. The total study duration will be up to of 1 year and 2 months per participant. The study consists of 3 parts: Screening (that is, up to 35 days before study commences on Day 1); Treatment (1 year) and post-treatment (30 days). Safety will primarily be evaluated by percentage of participants with kidney stones and change from baseline in bone mineral density at Month 12.
Interventions
DRUGTopiramate
Topiramate weight based dosing for participants 2 to \<10 years of age not to exceed 350 mg/day, as tolerated; not to exceed 400 mg/day in participants 10-15 years of age, as tolerated.
DRUGLevetiracetam
Levetiracetam weight based dosing for all participants 2-15 years of age, not to exceed 60 mg/kg/day, as tolerated. The maximum recommended daily dosage is 3,000 mg.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 15 Years
Healthy volunteers
No
Inclusion criteria
* Participant with a clinical diagnosis of new-onset or recent-onset epilepsy characterized by partial-onset seizures (POS) (with or without secondary generalization) or primary generalized tonic-clonic seizures (PGTCS) in accordance with criteria of the International League Against Epilepsy. The epilepsy diagnosis must be within the previous 2 years before screening * Caregivers (parents or legally acceptable representatives) of the participant must be able to accurately maintain the participant take-home record and seizure diary * At screening, participant must have weight and height values within the 5th to 95th percentile for chronological age (based on standard Child Height and Weight Charts from the Centers for Disease Control \[CDC\]) * Participant must never have been treated for epilepsy (treatment-naïve) or have been treated with no more than 1 standard antiepileptic drug (AED) if temporary or urgent AED use was necessary. Previous AED exposure must not exceed either of the following: 1.)Thirty-one days immediately preceding enrollment, or 2.)A total of 6 months of previous AED exposure in the past if the AED has been discontinued for at least 1 year prior to enrollment * Parents (or legally acceptable representatives) of the participant must sign an informed consent/permission document, indicating that they understand the purpose of and procedures required for the study and are willing to give permission for their child to participate in the study. Participant 7 years of age and older, capable of understanding the nature of the study, must provide assent for their participation
Exclusion criteria
* Participant has a surgically implanted and functioning vagus nerve stimulator * Participant has a history of seizures as a result of a correctable medical condition, such as metabolic disturbance, toxic exposure, neoplasm, or active infection within 2 weeks prior to the first day of Screening * Participant has had uncontrolled seizures while previously taking either topiramate or levetiracetam * Participant has a history of non-epileptic seizures within 2 weeks prior to the first day of Screening * Participant has myoclonic or absence seizures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in BMC-Z Score up to Month 12 | Baseline up to Month 12 | The BMC is an estimate of the amount of mineral (such as calcium) in the bone, which was assessed by DEXA scan for the posterior-anterior lumbar spine (L1\_L4) and total body less head area. Positive changes from baseline indicated an improvement in condition. |
| Change From Baseline in BMD Z-score up to Month 12 | Baseline up to Month 12 | The BMD was measured by DEXA for the posterior-anterior lumbar spine (L1\_L4) and total body less head area. The Z-Score is the number of standard deviations a participant's BMD differs from the average BMD of their age, sex and ethnicity. Positive scores indicate BMD above the mean; positive values are best values and negative values are worst values. Positive changes from baseline indicated an improvement in condition. |
| Change From Baseline in Bone Mineral Content (BMC)-Z Score up to Month 6 | Baseline up to Month 6 | The BMC is an estimate of the amount of mineral (such as calcium) in the bone, which was assessed by DEXA scan for the posterior-anterior lumbar spine (L1\_L4) and total body less head area. Positive changes from baseline indicated an improvement in condition. |
| Change From Baseline in Weight Z-score up to Month 1 | Baseline up to Month 1 | The Z-Score indicates how many standard deviations (SD) a participant has from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the Statistical Analysis System (SAS) programs provided by the Centers for Disease Control (CDC) for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 1 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. |
| Change From Baseline in Weight Z-score up to Month 3 | Baseline up to Month 3 | The Z-Score indicates how many SD a participant has from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the SAS programs provided by the CDC for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 3 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. |
| Change From Baseline in Weight Z-score up to Month 6 | Baseline up to Month 6 | The Z-Score indicates how many SD a participant has from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the SAS programs provided by the CDC for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 6 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. |
| Change From Baseline in Weight Z-score up to Month 9 | Baseline up to Month 9 | The Z-Score indicates how many SD a participant has from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the SAS programs provided by the CDC for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline up yo Month 9 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. |
| Change From Baseline in Weight Z-score up to Month 12 | Baseline up to Month 12 | The Z-Score indicates how many SD a participant has from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the SAS programs provided by the CDC for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline to Month 12 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. |
| Change From Baseline in Height Z-score up to Month 1 | Baseline up to Month 1 | Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from minus (-) 3 to plus (+) 3; 0 equal to (=) same mean, greater than (\>) 0 a greater mean, and less than (\<) 0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 1 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. |
| Change From Baseline in Height Z-score up to Month 3 | Baseline up to Month 3 | Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from -3 to +3; 0 =same mean, \>0 a greater mean, and \<0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 3 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. |
| Change From Baseline in Height Z-score up to Month 6 | Baseline up to Month 6 | Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from -3 to +3; 0 =same mean, \>0 a greater mean, and \<0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 6 for the total safety population for all age cohorts combined were presented. |
| Change From Baseline in Height Z-score up to Month 9 | Baseline up to Month 9 | Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from -3 to +3; 0 =same mean, \>0 a greater mean, and \<0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 9 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. |
| Change From Baseline in Height Z-score up to Month 12 | Baseline up to Month 12 | Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from -3 to +3; 0 =same mean, \>0 a greater mean, and \<0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 12 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. |
| Change From Baseline in Bone Mineral Density (BMD) Z-score up to Month 6 | Baseline up to Month 6 | The BMD was measured by dual energy X-ray absorptiometry (DEXA) for the posterior-anterior lumbar spine (L1\_L4) and total body less head area. The Z-Score is the number of standard deviations a participant's BMD differs from the average BMD of their age, sex and ethnicity. Positive scores indicate BMD above the mean; positive values are best values and negative values are worst values. Positive changes from baseline indicated an improvement in condition. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Kidney Stones | Up to Day 390 | Percentage of participants with kidney stones were reported. |
| Number of Participants With Treatment-emergent Adverse Events (TEAE) | Up to Day 390 | An adverse event (AE) is any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. TEAE are defined as AEs with onset during the treatment period or that are a consequence of a pre-existing condition that has worsened since baseline. |
Countries
Argentina, Australia, Austria, Belgium, Canada, France, Germany, Hungary, Philippines, Poland, Russia, South Africa, Taiwan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Topiramate Participants received topiramate weight-based sprinkle capsule and tablet, as tolerated (not to exceed 350 milligrams per day \[mg/day\] for participants 2 to less than \[\<\] 10 years of age, and not to exceed 400 mg/day for participants 10 to 15 years of age), twice daily (BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available topiramate or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days. | 28 |
| Levetiracetam Participants received levetiracetam weight-based tablet or oral solution, as tolerated (not to exceed 60 milligrams per kilogram per day \[mg/kg/day\] for participants 2 to 15 years of age). The daily dosage was increased every 2 weeks by increments of 20 mg/kg/day to the recommended daily dosage of 60 mg/kg/day. The maximum recommended daily dosage was 3000 mg (1500 mg BID) for up to 1 year during open-label treatment phase. Participants were to either continue on commercially available levetiracetam or were tapered off of study drug over a period of up to 2 weeks during post-treatment phase of 30 days. | 35 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Noncompliance with Study Drug | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Topiramate | Levetiracetam | Total |
|---|---|---|---|
| Age, Continuous | 9.9 years STANDARD_DEVIATION 2.76 | 9.3 years STANDARD_DEVIATION 3.29 | 9.6 years STANDARD_DEVIATION 3.05 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 10 Participants | 10 Participants | 20 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 18 Participants | 25 Participants | 43 Participants |
| Region of Enrollment AUSTRIA | 0 Participants | 2 Participants | 2 Participants |
| Region of Enrollment CANADA | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment HUNGARY | 4 Participants | 5 Participants | 9 Participants |
| Region of Enrollment ITALY | 3 Participants | 4 Participants | 7 Participants |
| Region of Enrollment PHILIPPINES | 1 Participants | 2 Participants | 3 Participants |
| Region of Enrollment POLAND | 8 Participants | 8 Participants | 16 Participants |
| Region of Enrollment RUSSIAN FEDERATION | 2 Participants | 4 Participants | 6 Participants |
| Region of Enrollment TAIWAN | 9 Participants | 8 Participants | 17 Participants |
| Region of Enrollment UNITED STATES | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Female | 16 Participants | 18 Participants | 34 Participants |
| Sex: Female, Male Male | 12 Participants | 17 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 35 |
| other Total, other adverse events | 25 / 28 | 29 / 35 |
| serious Total, serious adverse events | 0 / 28 | 5 / 35 |
Outcome results
Primary
Change From Baseline in BMC-Z Score up to Month 12
The BMC is an estimate of the amount of mineral (such as calcium) in the bone, which was assessed by DEXA scan for the posterior-anterior lumbar spine (L1\_L4) and total body less head area. Positive changes from baseline indicated an improvement in condition.
Time frame: Baseline up to Month 12
Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here 'N' (number of participants analyzed) signifies the number of participants evaluable for this outcome measure. Here, 'n' (number analyzed) signifies the number of participants evaluable at a specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Topiramate | Change From Baseline in BMC-Z Score up to Month 12 | Lumbar spine | -0.274 Z-score | Standard Deviation 0.3123 |
| Topiramate | Change From Baseline in BMC-Z Score up to Month 12 | Total body less head | -0.266 Z-score | Standard Deviation 0.68 |
| Levetiracetam | Change From Baseline in BMC-Z Score up to Month 12 | Lumbar spine | 0.124 Z-score | Standard Deviation 0.3584 |
| Levetiracetam | Change From Baseline in BMC-Z Score up to Month 12 | Total body less head | 0.017 Z-score | Standard Deviation 0.2533 |
Primary
Change From Baseline in BMD Z-score up to Month 12
The BMD was measured by DEXA for the posterior-anterior lumbar spine (L1\_L4) and total body less head area. The Z-Score is the number of standard deviations a participant's BMD differs from the average BMD of their age, sex and ethnicity. Positive scores indicate BMD above the mean; positive values are best values and negative values are worst values. Positive changes from baseline indicated an improvement in condition.
Time frame: Baseline up to Month 12
Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here 'N' (number of participants analyzed) signifies the number of participants evaluable for this outcome measure. Here, 'n' (number analyzed) signifies the number of participants evaluable at a specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Topiramate | Change From Baseline in BMD Z-score up to Month 12 | Lumbar spine | -0.346 Z-score | Standard Deviation 0.3461 |
| Topiramate | Change From Baseline in BMD Z-score up to Month 12 | Total body less head | -0.367 Z-score | Standard Deviation 0.317 |
| Levetiracetam | Change From Baseline in BMD Z-score up to Month 12 | Lumbar spine | 0.084 Z-score | Standard Deviation 0.3552 |
| Levetiracetam | Change From Baseline in BMD Z-score up to Month 12 | Total body less head | 0.054 Z-score | Standard Deviation 0.3766 |
Primary
Change From Baseline in Bone Mineral Content (BMC)-Z Score up to Month 6
The BMC is an estimate of the amount of mineral (such as calcium) in the bone, which was assessed by DEXA scan for the posterior-anterior lumbar spine (L1\_L4) and total body less head area. Positive changes from baseline indicated an improvement in condition.
Time frame: Baseline up to Month 6
Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here 'N' (number of participants analyzed) signifies the number of participants evaluable for this outcome measure. Here, 'n' (number analyzed) signifies the number of participants evaluable at a specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Topiramate | Change From Baseline in Bone Mineral Content (BMC)-Z Score up to Month 6 | Lumbar spine | -0.141 Z-score | Standard Deviation 0.2155 |
| Topiramate | Change From Baseline in Bone Mineral Content (BMC)-Z Score up to Month 6 | Total body less head | -0.242 Z-score | Standard Deviation 0.2516 |
| Levetiracetam | Change From Baseline in Bone Mineral Content (BMC)-Z Score up to Month 6 | Lumbar spine | 0.075 Z-score | Standard Deviation 0.2806 |
| Levetiracetam | Change From Baseline in Bone Mineral Content (BMC)-Z Score up to Month 6 | Total body less head | 0.151 Z-score | Standard Deviation 0.2154 |
Primary
Change From Baseline in Bone Mineral Density (BMD) Z-score up to Month 6
The BMD was measured by dual energy X-ray absorptiometry (DEXA) for the posterior-anterior lumbar spine (L1\_L4) and total body less head area. The Z-Score is the number of standard deviations a participant's BMD differs from the average BMD of their age, sex and ethnicity. Positive scores indicate BMD above the mean; positive values are best values and negative values are worst values. Positive changes from baseline indicated an improvement in condition.
Time frame: Baseline up to Month 6
Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here 'N' (number of participants analyzed) signifies the number of participants evaluable for this outcome measure. Here, 'n' (number analyzed) signifies the number of participants evaluable for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Topiramate | Change From Baseline in Bone Mineral Density (BMD) Z-score up to Month 6 | Lumbar spine | -0.181 Z-score | Standard Deviation 0.259 |
| Topiramate | Change From Baseline in Bone Mineral Density (BMD) Z-score up to Month 6 | Total body less head | -0.180 Z-score | Standard Deviation 0.2647 |
| Levetiracetam | Change From Baseline in Bone Mineral Density (BMD) Z-score up to Month 6 | Lumbar spine | 0.035 Z-score | Standard Deviation 0.2606 |
| Levetiracetam | Change From Baseline in Bone Mineral Density (BMD) Z-score up to Month 6 | Total body less head | 0.102 Z-score | Standard Deviation 0.2574 |
Primary
Change From Baseline in Height Z-score up to Month 1
Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from minus (-) 3 to plus (+) 3; 0 equal to (=) same mean, greater than (\>) 0 a greater mean, and less than (\<) 0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 1 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.
Time frame: Baseline up to Month 1
Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topiramate | Change From Baseline in Height Z-score up to Month 1 | 0.004 Z-score | Standard Deviation 0.087 |
| Levetiracetam | Change From Baseline in Height Z-score up to Month 1 | -0.015 Z-score | Standard Deviation 0.1017 |
Primary
Change From Baseline in Height Z-score up to Month 12
Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from -3 to +3; 0 =same mean, \>0 a greater mean, and \<0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 12 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.
Time frame: Baseline up to Month 12
Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topiramate | Change From Baseline in Height Z-score up to Month 12 | -0.057 Z-score | Standard Deviation 0.2734 |
| Levetiracetam | Change From Baseline in Height Z-score up to Month 12 | 0.088 Z-score | Standard Deviation 0.3315 |
Primary
Change From Baseline in Height Z-score up to Month 3
Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from -3 to +3; 0 =same mean, \>0 a greater mean, and \<0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 3 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.
Time frame: Baseline up to Month 3
Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topiramate | Change From Baseline in Height Z-score up to Month 3 | -0.036 Z-score | Standard Deviation 0.1452 |
| Levetiracetam | Change From Baseline in Height Z-score up to Month 3 | 0.017 Z-score | Standard Deviation 0.1631 |
Primary
Change From Baseline in Height Z-score up to Month 6
Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from -3 to +3; 0 =same mean, \>0 a greater mean, and \<0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 6 for the total safety population for all age cohorts combined were presented.
Time frame: Baseline up to Month 6
Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topiramate | Change From Baseline in Height Z-score up to Month 6 | -0.008 Z-score | Standard Deviation 0.1753 |
| Levetiracetam | Change From Baseline in Height Z-score up to Month 6 | 0.077 Z-score | Standard Deviation 0.267 |
Primary
Change From Baseline in Height Z-score up to Month 9
Z-Score was a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean was above or below the standard and how unusual the measurement is with range from -3 to +3; 0 =same mean, \>0 a greater mean, and \<0 a lesser mean than the standard. Growth parameters were compared to a standard defined by CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 9 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.
Time frame: Baseline up to Month 9
Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topiramate | Change From Baseline in Height Z-score up to Month 9 | -0.059 Z-score | Standard Deviation 0.2337 |
| Levetiracetam | Change From Baseline in Height Z-score up to Month 9 | 0.086 Z-score | Standard Deviation 0.2929 |
Primary
Change From Baseline in Weight Z-score up to Month 1
The Z-Score indicates how many standard deviations (SD) a participant has from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the Statistical Analysis System (SAS) programs provided by the Centers for Disease Control (CDC) for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 1 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.
Time frame: Baseline up to Month 1
Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topiramate | Change From Baseline in Weight Z-score up to Month 1 | -0.112 Z-score | Standard Deviation 0.122 |
| Levetiracetam | Change From Baseline in Weight Z-score up to Month 1 | -0.014 Z-score | Standard Deviation 0.1244 |
Primary
Change From Baseline in Weight Z-score up to Month 12
The Z-Score indicates how many SD a participant has from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the SAS programs provided by the CDC for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline to Month 12 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.
Time frame: Baseline up to Month 12
Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topiramate | Change From Baseline in Weight Z-score up to Month 12 | -0.351 Z-score | Standard Deviation 0.3905 |
| Levetiracetam | Change From Baseline in Weight Z-score up to Month 12 | -0.065 Z-score | Standard Deviation 0.3026 |
Primary
Change From Baseline in Weight Z-score up to Month 3
The Z-Score indicates how many SD a participant has from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the SAS programs provided by the CDC for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 3 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.
Time frame: Baseline up to Month 3
Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topiramate | Change From Baseline in Weight Z-score up to Month 3 | -0.201 Z-score | Standard Deviation 0.2094 |
| Levetiracetam | Change From Baseline in Weight Z-score up to Month 3 | -0.027 Z-score | Standard Deviation 0.1802 |
Primary
Change From Baseline in Weight Z-score up to Month 6
The Z-Score indicates how many SD a participant has from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the SAS programs provided by the CDC for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline up to Month 6 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.
Time frame: Baseline up to Month 6
Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topiramate | Change From Baseline in Weight Z-score up to Month 6 | -0.319 Z-score | Standard Deviation 0.2496 |
| Levetiracetam | Change From Baseline in Weight Z-score up to Month 6 | -0.070 Z-score | Standard Deviation 0.2304 |
Primary
Change From Baseline in Weight Z-score up to Month 9
The Z-Score indicates how many SD a participant has from the population normal values. The body weight z-scores were designed to take into account the amount of weight gain that was expected due to normal growth in children and adolescents. Body weight data were converted to Z-scores using the SAS programs provided by the CDC for the calculation of the 2000 CDC growth charts. The mean (SD) change in Z scores from baseline up yo Month 9 for the total safety population for all age cohorts combined were presented. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.
Time frame: Baseline up to Month 9
Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topiramate | Change From Baseline in Weight Z-score up to Month 9 | -0.326 Z-score | Standard Deviation 0.3235 |
| Levetiracetam | Change From Baseline in Weight Z-score up to Month 9 | -0.110 Z-score | Standard Deviation 0.3584 |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAE)
An adverse event (AE) is any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. TEAE are defined as AEs with onset during the treatment period or that are a consequence of a pre-existing condition that has worsened since baseline.
Time frame: Up to Day 390
Population: Safety analysis set included all randomized participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Topiramate | Number of Participants With Treatment-emergent Adverse Events (TEAE) | 25 Participants |
| Levetiracetam | Number of Participants With Treatment-emergent Adverse Events (TEAE) | 29 Participants |
Secondary
Percentage of Participants With Kidney Stones
Percentage of participants with kidney stones were reported.
Time frame: Up to Day 390
Population: Safety analysis set included all randomized subjects who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Topiramate | Percentage of Participants With Kidney Stones | 0 percentage of participants |
| Levetiracetam | Percentage of Participants With Kidney Stones | 0 percentage of participants |