Trial Outcomes & Findings for A Study to Investigate the Safety of the Drugs Topiramate and Levetiracetam in Treating Children Recently Diagnosed With Epilepsy (NCT NCT02201251)

NCT ID: NCT02201251

Last Updated: 2025-04-29

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

63 participants

Primary outcome timeframe

Baseline up to Month 1

Results posted on

2025-04-29

Participant Flow

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	28	35
Overall Study COMPLETED	24	32
Overall Study NOT COMPLETED	4	3

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Adverse Event	1	1
Overall Study Protocol Violation	1	0
Overall Study Noncompliance with Study Drug	0	1
Overall Study Withdrawal by Subject	2	1

Baseline Characteristics

A Study to Investigate the Safety of the Drugs Topiramate and Levetiracetam in Treating Children Recently Diagnosed With Epilepsy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Topiramate n=28 Participants 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.	Levetiracetam n=35 Participants 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.	Total n=63 Participants Total of all reporting groups
Age, Continuous	9.9 years STANDARD_DEVIATION 2.76 • n=5 Participants	9.3 years STANDARD_DEVIATION 3.29 • n=7 Participants	9.6 years STANDARD_DEVIATION 3.05 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	18 Participants n=7 Participants	34 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	17 Participants n=7 Participants	29 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	18 Participants n=5 Participants	25 Participants n=7 Participants	43 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment AUSTRIA	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment CANADA	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment HUNGARY	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Region of Enrollment ITALY	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment PHILIPPINES	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment POLAND	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants
Region of Enrollment RUSSIAN FEDERATION	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment TAIWAN	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Region of Enrollment UNITED STATES	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Topiramate n=27 Participants 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.	Levetiracetam n=34 Participants 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.
Change From Baseline in Weight Z-score up to Month 1	-0.112 Z-score Standard Deviation 0.1220 • Interval 0.122 to	-0.014 Z-score Standard Deviation 0.1244 • Interval 0.1244 to

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Topiramate n=27 Participants 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.	Levetiracetam n=34 Participants 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.
Change From Baseline in Weight Z-score up to Month 3	-0.201 Z-score Standard Deviation 0.2094 • Interval 0.2094 to	-0.027 Z-score Standard Deviation 0.1802 • Interval 0.1802 to

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Topiramate n=24 Participants 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.	Levetiracetam n=33 Participants 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.
Change From Baseline in Weight Z-score up to Month 6	-0.319 Z-score Standard Deviation 0.2496 • Interval 0.2496 to	-0.070 Z-score Standard Deviation 0.2304 • Interval 0.2304 to

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Topiramate n=24 Participants 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.	Levetiracetam n=32 Participants 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.
Change From Baseline in Weight Z-score up to Month 9	-0.326 Z-score Standard Deviation 0.3235 • Interval 0.3235 to	-0.110 Z-score Standard Deviation 0.3584 • Interval 0.3584 to

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Topiramate n=24 Participants 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.	Levetiracetam n=32 Participants 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.
Change From Baseline in Weight Z-score up to Month 12	-0.351 Z-score Standard Deviation 0.3905 • Interval 0.3905 to	-0.065 Z-score Standard Deviation 0.3026 • Interval 0.3026 to

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Topiramate n=27 Participants 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.	Levetiracetam n=33 Participants 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.
Change From Baseline in Height Z-score up to Month 1	0.004 Z-score Standard Deviation 0.0870 • Interval 0.087 to	-0.015 Z-score Standard Deviation 0.1017 • Interval 0.1017 to

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Topiramate n=27 Participants 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.	Levetiracetam n=34 Participants 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.
Change From Baseline in Height Z-score up to Month 3	-0.036 Z-score Standard Deviation 0.1452 • Interval 0.1452 to	0.017 Z-score Standard Deviation 0.1631 • Interval 0.1631 to

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Topiramate n=24 Participants 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.	Levetiracetam n=33 Participants 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.
Change From Baseline in Height Z-score up to Month 6	-0.008 Z-score Standard Deviation 0.1753 • Interval 0.1753 to	0.077 Z-score Standard Deviation 0.2670 • Interval 0.267 to

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Topiramate n=24 Participants 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.	Levetiracetam n=32 Participants 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.
Change From Baseline in Height Z-score up to Month 9	-0.059 Z-score Standard Deviation 0.2337 • Interval 0.2337 to	0.086 Z-score Standard Deviation 0.2929 • Interval 0.2929 to

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Topiramate n=24 Participants 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.	Levetiracetam n=32 Participants 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.
Change From Baseline in Height Z-score up to Month 12	-0.057 Z-score Standard Deviation 0.2734 • Interval 0.2734 to	0.088 Z-score Standard Deviation 0.3315 • Interval 0.3315 to

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Topiramate n=25 Participants 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.	Levetiracetam n=32 Participants 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.
Change From Baseline in Bone Mineral Density (BMD) Z-score up to Month 6 Lumbar spine	-0.181 Z-score Standard Deviation 0.2590	0.035 Z-score Standard Deviation 0.2606
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	0.102 Z-score Standard Deviation 0.2574

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Topiramate n=24 Participants 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.	Levetiracetam n=30 Participants 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.
Change From Baseline in BMD Z-score up to Month 12 Total body less head	-0.367 Z-score Standard Deviation 0.3170	0.054 Z-score Standard Deviation 0.3766
Change From Baseline in BMD Z-score up to Month 12 Lumbar spine	-0.346 Z-score Standard Deviation 0.3461	0.084 Z-score Standard Deviation 0.3552

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Topiramate n=15 Participants 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.	Levetiracetam n=19 Participants 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.
Change From Baseline in Bone Mineral Content (BMC)-Z Score up to Month 6 Lumbar spine	-0.141 Z-score Standard Deviation 0.2155	0.075 Z-score Standard Deviation 0.2806
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	0.151 Z-score Standard Deviation 0.2154

PRIMARY outcome

Timeframe: Baseline up to Month 12

Outcome measures

Outcome measures
Measure	Topiramate n=15 Participants 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.	Levetiracetam n=18 Participants 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.
Change From Baseline in BMC-Z Score up to Month 12 Lumbar spine	-0.274 Z-score Standard Deviation 0.3123	0.124 Z-score Standard Deviation 0.3584
Change From Baseline in BMC-Z Score up to Month 12 Total body less head	-0.266 Z-score Standard Deviation 0.6800	0.017 Z-score Standard Deviation 0.2533

SECONDARY outcome

Timeframe: Up to Day 390

Population: Safety analysis set included all randomized participants who received at least 1 dose of study treatment.

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.

Outcome measures

Outcome measures
Measure	Topiramate n=28 Participants 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.	Levetiracetam n=35 Participants 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.
Number of Participants With Treatment-emergent Adverse Events (TEAE)	25 Participants	29 Participants

SECONDARY outcome

Timeframe: Up to Day 390

Population: Safety analysis set included all randomized subjects who received at least 1 dose of study treatment.

Percentage of participants with kidney stones were reported.

Outcome measures

Outcome measures
Measure	Topiramate n=28 Participants 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.	Levetiracetam n=35 Participants 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.
Percentage of Participants With Kidney Stones	0 percentage of participants	0 percentage of participants

Adverse Events

Topiramate

Serious events: 0 serious events

Other events: 25 other events

Deaths: 0 deaths

Levetiracetam

Serious events: 5 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Topiramate n=28 participants at risk 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.	Levetiracetam n=35 participants at risk 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.
Injury, poisoning and procedural complications Skull Fracture	0.00% 0/28 • Up to Day 390 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	2.9% 1/35 • Up to Day 390 The safety analysis set included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Myositis	0.00% 0/28 • Up to Day 390 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	2.9% 1/35 • Up to Day 390 The safety analysis set included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Epilepsy	0.00% 0/28 • Up to Day 390 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	2.9% 1/35 • Up to Day 390 The safety analysis set included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Generalised Tonic-Clonic Seizure	0.00% 0/28 • Up to Day 390 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	2.9% 1/35 • Up to Day 390 The safety analysis set included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Seizure	0.00% 0/28 • Up to Day 390 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	2.9% 1/35 • Up to Day 390 The safety analysis set included all randomized participants who received at least 1 dose of study drug.

Other adverse events

Additional Information

Director - Clinical Leader

Janssen Research & Development, LLC

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
Publication restrictions are in place

Restriction type: OTHER