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

NCT02201251 | Completed Phase 3 Results DMC

• 3 other identifiers: CR104425TOPMATEPY40672012-001552-19
• Study Type: interventional
• Target: 63
• Locations: 13 countries
• Sites: 40

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.

Conditions

Epilepsy

Keywords

Epilepsy; Topiramate; Levetiracetam; Pediatric

Outcome Measures

Primary Outcomes (14)

• 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.

  Baseline up to Month 1

• 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.

  Baseline up to Month 3

• 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.

  Baseline up to Month 6

• 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.

  Baseline up to Month 9

• 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.

  Baseline up to Month 12

• 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.

  Baseline up to Month 1

• 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.

  Baseline up to Month 3

• 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.

  Baseline up to Month 6

• 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.

  Baseline up to Month 9

• 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.

  Baseline up to Month 12

• 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.

  Baseline up to Month 6

• 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.

  Baseline up to Month 12

• 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.

  Baseline up to Month 6

• 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.

  Baseline up to Month 12

Secondary Outcomes (2)

• Number of Participants With Treatment-emergent Adverse Events (TEAE)

  Up to Day 390

• Percentage of Participants With Kidney Stones

  Up to Day 390

Study Arms (2)

Topiramate

EXPERIMENTAL

Topiramate weight based dosing for participants 2 to less than (\<) 10 years of age not to exceed 350 mg/day (milligram per day), as tolerated; not to exceed 400 mg/day in participants 10-15 years of age, as tolerated.

Drug: Topiramate

Levetiracetam

ACTIVE COMPARATOR

Levetiracetam weight based dosing for all participants 2-15 years of age, not to exceed 60 milligram per kilogram per day (mg/kg/day), as tolerated. The maximum recommended daily dosage is 3,000 milligram (mg).

Drug: Levetiracetam

Interventions

Topiramate DRUG

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.

Topiramate

Levetiracetam DRUG

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.

Levetiracetam

Eligibility Criteria

• Age: 2 Years - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (41)

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Birmingham, Alabama, United States

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Los Angeles, California, United States

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Gulf Breeze, Florida, United States

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Orlando, Florida, United States

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Tampa, Florida, United States

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Wellington, Florida, United States

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Louisville, Kentucky, United States

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Columbus, Ohio, United States

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Toledo, Ohio, United States

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Portland, Oregon, United States

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San Antonio, Texas, United States

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Temple, Texas, United States

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Buenos Aires, Argentina

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Córdoba, Argentina

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Queensland, Australia

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Graz, Austria

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Leuven, Belgium

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Namur, Belgium

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Saskatoon, Saskatchewan, Canada

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Brest, France

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Bron, France

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Paris, France

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Toulouse, France

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München, Germany

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Tübingen, Germany

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Balassagyarmat, Hungary

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Budapest, Hungary

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Debrecen, Hungary

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Veszprém, Hungary

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Cebu, Philippines

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Manila, Philippines

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Krakow, Poland

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Poznan, Poland

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Warsaw, Poland

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Saint Petersburg, Russia

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Ulyanovsk, Russia

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Durban, South Africa

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Kaohsiung City, Taiwan

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New Taipei City, Taiwan

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Taichung, Taiwan

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Taipei, Taiwan

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MeSH Terms

Conditions

Epilepsy

Interventions

Topiramate; Levetiracetam

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Fructose; Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses; Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Due to futility of enrollment, the enrollment was stopped early; however, all enrolled participants completed the full course of the trial excluding 7 participants (reasons captured in "participant flow"). Also, there was no exposure to topiramate in 2 to 5 years age cohort. Therefore, no conclusions can be made with regard to this age group due to the absence of comparability.

Results Point of Contact

• Title: Director - Clinical Leader
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2014
• First Posted: July 28, 2014
• Study Start: October 6, 2014
• Primary Completion: April 30, 2020
• Study Completion: April 30, 2020
• Last Updated: April 29, 2025
• Results First Posted: May 17, 2021

Record last verified: 2025-04

Locations

AR (2); AU (1); FR (4); HU (4); PL (3); BE (2); DE (2); RU (2); PH (2); US (12); ZA (1); CA (1); TW (4)