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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02201251
Recruitment Status : Recruiting
First Posted : July 28, 2014
Last Update Posted : November 15, 2018
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

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.

Condition or disease Intervention/treatment Phase
Epilepsy Drug: Topiramate Drug: Levetiracetam Phase 3

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 282 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Health Services Research
Official Title: A Randomized, Active-Controlled, Open-Label, Flexible-Dose Study to Assess the Safety and Tolerability of Topiramate as Monotherapy Compared With Levetiracetam as Monotherapy in Pediatric Subjects With New or Recent-Onset Epilepsy
Actual Study Start Date : October 6, 2014
Estimated Primary Completion Date : November 30, 2021
Estimated Study Completion Date : November 30, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Epilepsy

Arm Intervention/treatment
Experimental: Topiramate
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
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.

Active Comparator: Levetiracetam
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
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.




Primary Outcome Measures :
  1. Percentage of Participants With Kidney Stones [ Time Frame: Month 12 ]
    Percentage of participants with kidney stones will be assessed.

  2. Change From Baseline in Weight Z-score at Month 12 [ Time Frame: Baseline and Month 12 ]
    The Z-Score indicates how many standard deviations a participant is from the population norm values. The body weight z-scores are designed to take into account the amount of weight gain that would be expected due to normal growth in children and adolescents. The body weight z-scores are by age and gender standardized values (corresponding to a normal distribution with mean 0 and a standard deviation of 1) of the actual weight measurements. Change From Baseline is calculated as value at Month 12 minus value at Baseline.

  3. Height at Month 12 [ Time Frame: Month 12 ]
    Height analyses will be conducted at Month 12, for prepubertal participants (2 to 9 years of age), participants 10 to 15 years of age, and participants 2 to 15 years of age.

  4. Change From Baseline in Height at Month 12 [ Time Frame: Baseline and Month 12 ]
    Height analyses will be conducted at Month 12, for prepubertal participants (2 to 9 years of age), participants 10 to 15 years of age, and participants 2 to 15 years of age. Change From Baseline is calculated as value at Month 12 minus value at Baseline.

  5. Height Z-score at Month 12 [ Time Frame: Month 12 ]
    Standing height will be taken as a mean of 3 consecutive measurements using a wall mounted stadiometer. Z-Score will be a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean will be above or below the standard and how unusual the measurement is with range from -3 to +3; 0 =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 Centers for Disease Control's growth charts.

  6. Change From Baseline in Height Z-score at Month 12 [ Time Frame: Baseline and Month 12 ]
    Standing height will be taken as a mean of 3 consecutive measurements using a wall mounted stadiometer. Z-Score will be a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean will be 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 Centers for Disease Control's growth charts. Change From Baseline is calculated as value at Month 12 minus value at Baseline.

  7. Height Velocity (HV) at Month 12 [ Time Frame: Month 12 ]
    The HV is the change in height since the previous year´s measurement and more precisely: HV = {(h-hp)/(d-dp)} * 365.25 [centimeter (cm)/year] where h is current height in cm, hp is previous height in cm, closest to 1 year previous, d is the current date and dp is the date of measurement of previous height, closest to 1 year previous. Additionally, d and dp have to be within 0.6 years and 1.5 years. HV is the mean height velocity over the interval between d and dp but is displayed as HV at d.

  8. Height Velocity (HV) Z-score at Month 12 [ Time Frame: Month 12 ]
    The HV Z-score will be assessed.

  9. Percentage of Outlier Participants [ Time Frame: Month 12 ]
    Percentage of outlier participants with height Z-score decrease of > 0.5, >1.0, and >2.0 will be reported.

  10. Bone Mineral Density (BMD) [ Time Frame: Month 12 ]
    The BMD is measured by dual energy x-ray absorptiometry (DEXA). 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".

  11. Bone Mineral Content (BMC) [ Time Frame: Month 12 ]
    The BMC is an estimate of the amount of mineral (such as calcium) in the bone, which will be assessed by DEXA scan.

  12. Change From Baseline in Bone Mineral Density (BMD) at Month 12 [ Time Frame: Baseline and Month 12 ]
    The BMD is the amount of mineral per square centimeter of bone, which will be assessed by dual energy x-ray absorptiometry (DEXA) scan. Change From Baseline is calculated as value at Month 12 minus value at Baseline.

  13. Change From Baseline in Bone Mineral Content (BMC) at Month 12 [ Time Frame: Baseline and Month 12 ]
    The BMC is an estimate of the amount of mineral (such as calcium) in the bone, which will be assessed by DEXA scan. Change From Baseline is calculated as value at Month 12 minus value at Baseline.

  14. Bone Mineral Density (BMD)-Z Score [ Time Frame: Month 12 ]
    BMD is measured by dual energy x-ray absorptiometry (DEXA). The Z-Score is the number of standard deviations a participant's BMD differs from the average BMD of their age, sex and ethnicity.

  15. Bone Mineral Content (BMC) Z-Score [ Time Frame: Month 12 ]
    The BMC is measured by dual energy x-ray absorptiometry (DEXA). The Z-Score is the number of standard deviations a participant's BMC differs from the average BMC of their age, sex and ethnicity. Positive scores indicate BMC above the mean; Positive values are "best values" and negative values are "worst values".

  16. Change From Baseline in Bone Mineral Density (BMD)-Z Score at Month 12 [ Time Frame: Baseline and Month 12 ]
    The BMD is measured by DEXA. 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". Change From Baseline is calculated as value at Month 12 minus value at Baseline.

  17. Change From Baseline in Bone Mineral Content (BMC) Z-Score at Month 12 [ Time Frame: Baseline and Month 12 ]
    The BMC is measured by DEXA. The Z-Score is the number of standard deviations a participant's BMC differs from the average BMC of their age, sex and ethnicity. Positive scores indicate BMC above the mean; Positive values are "best values" and negative values are "worst values". Change From Baseline is calculated as value at Month 12 minus value at Baseline.

  18. Percent Change From Baseline in Bone Mineral Density (BMD) at Month 12 [ Time Frame: Baseline and Month 12 ]
    The BMD is the amount of mineral per square centimeter of bone, which will be assessed by DEXA scan. Percent change from baseline in BMD at Month 12 will be reported.

  19. Percent Change From Baseline in Bone Mineral Content (BMC) at Month 12 [ Time Frame: Baseline and Month 12 ]
    The BMC is an estimate of the amount of mineral (such as calcium) in the bone, which will be assessed by DEXA scan. Percent change from baseline in BMD will be reported.

  20. Percentage of Outlier Participants with BMD Z-score [ Time Frame: Month 12 ]
    Percentage of outlier participants with BMD Z-score decrease of > 0.5, >1.0, and >2.0 will be reported.

  21. Change From Baseline in Biochemical Markers at Month 12 [ Time Frame: Baseline and Month 12 ]
    Biochemical markers of bone mineralization will include alkaline phosphatase, calcium, phosphorus, parathyroid hormone (intact), 25-hydroxy- vitamin D, 1,25-dihyroxy vitamin D, and insulin-like growth factor-1 (IGF-1). Change From Baseline is calculated as value at Month 12 minus value at Baseline.

  22. Change From Screening in Serum Laboratory Tests at Month 12 [ Time Frame: Screening and Month 12 ]
    Change from screening in serum laboratory tests will be summarized over time.

  23. Change From Baseline in Bone Age at Month 12 [ Time Frame: Baseline and Month 12 ]
    A hand or wrist x-ray will be obtained in the non-dominant hand or wrist to determine bone age at Baseline and at Month 12

  24. Change From Screening in Urine Laboratory Tests at Month 12 [ Time Frame: Screening and Month 12 ]
    Change from screening in urine laboratory tests will be summarized over time.


Secondary Outcome Measures :
  1. Change From Baseline in Weight Z-score at Month 1, 3, 6 and 9 [ Time Frame: Baseline, Month 1, 3, 6 and 9 ]
    The Z-Score indicates how many standard deviations a participant is from the population norm values. The body weight z-scores are designed to take into account the amount of weight gain that would be expected due to normal growth in children and adolescents. The body weight z-scores are by age and gender standardized values (corresponding to a normal distribution with mean 0 and a standard deviation of 1) of the actual weight measurements.

  2. Change From Baseline in Height at Month 1, 3, 6 and 9 [ Time Frame: Baseline, Month 1, 3, 6 and 9 ]
    Height analyses will be conducted at Month 12, for prepubertal participants (2 to 9 years of age), participants 10 to 15 years of age, and participants 2 to 15 years of age.

  3. Change From Baseline in Height Z-score at Month 1, 3, 6 and 9 [ Time Frame: Baseline, Month 1, 3, 6 and 9 ]
    Standing height will be taken as a mean of 3 consecutive measurements using a wall mounted stadiometer. Z-Score will be a statistical measure to evaluate how a single data point compares to a standard. It described whether a mean will be 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 Centers for Disease Control's growth charts.

  4. Percentage of Outlier Participants [ Time Frame: Month 1, 3, 6 and 9 ]
    Percentage of outlier participants with height Z-score decrease of > 0.5, >1.0, and >2.0 will be reported.

  5. Bone Mineral Density (BMD) [ Time Frame: Month 6 ]
    The BMD is measured by DEXA. 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".

  6. Bone Mineral Content (BMC) [ Time Frame: Month 6 ]
    The BMC is an estimate of the amount of mineral (such as calcium) in the bone, which will be assessed by DEXA scan.

  7. Change From Baseline in Bone Mineral Density (BMD) at Month 6 [ Time Frame: Baseline and Month 6 ]
    The BMD is the amount of mineral per square centimeter of bone, which will be assessed by dual energy x-ray absorptiometry (DEXA) scan.

  8. Change From Baseline in Bone Mineral Content (BMC) at Month 6 [ Time Frame: Baseline and Month 6 ]
    The BMC is an estimate of the amount of mineral (such as calcium) in the bone, which will be assessed by DEXA scan.

  9. Bone Mineral Density (BMD)-Z Score [ Time Frame: Month 6 ]
    BMD is measured by DEXA. The Z-Score is the number of standard deviations a participant's BMD differs from the average BMD of their age, sex and ethnicity.

  10. Bone Mineral Content (BMC) Z-Score [ Time Frame: Month 6 ]
    The BMC is measured by DEXA. The Z-Score is the number of standard deviations a participant's BMC differs from the average BMC of their age, sex and ethnicity. Positive scores indicate BMC above the mean; Positive values are "best values" and negative values are "worst values".

  11. Change From Baseline in Bone Mineral Density (BMD)-Z Score at Month 6 [ Time Frame: Baseline and Month 6 ]
    The BMD is measured by DEXA. 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".

  12. Change From Baseline in Bone Mineral Content (BMC) Z-Score at Month 6 [ Time Frame: Baseline and Month 6 ]
    The BMC is measured by dual energy x-ray absorptiometry (DEXA). The Z-Score is the number of standard deviations a participant's BMC differs from the average BMC of their age, sex and ethnicity. Positive scores indicate BMC above the mean; Positive values are "best values" and negative values are "worst values".

  13. Percent Change From Baseline in Bone Mineral Density (BMD) at Month 6 [ Time Frame: Baseline and Month 6 ]
    The BMD is the amount of mineral per square centimeter of bone, which will be assessed by DEXA scan. Percent change from baseline in BMD at Month 6 will be reported.

  14. Percent Change From Baseline in Bone Mineral Content (BMC) at Month 6 [ Time Frame: Baseline and Month 6 ]
    The BMC is an estimate of the amount of mineral (such as calcium) in the bone, which will be assessed by DEXA scan. Percent change from baseline in BMD will be reported.

  15. Percentage of Outlier Participants with BMD Z-score [ Time Frame: Month 6 ]
    Percentage of outlier participants with BMD Z-score decrease of > 0.5, >1.0, and >2.0 will be reported.

  16. Change From Baseline in Biochemical Markers at Month 6 [ Time Frame: Baseline and Month 6 ]
    Biochemical markers of bone mineralization will include alkaline phosphatase, calcium, phosphorus, parathyroid hormone (intact), 25-hydroxy- vitamin D, 1,25-dihyroxy vitamin D, and insulin-like growth factor-1 (IGF-1).

  17. Change From Screening in Laboratory Tests at Month 1, 3, 6 and 9 [ Time Frame: Screening, Month 1, 3, 6 and 9 ]
    Change from screening in serum laboratory tests will be summarized over time.

  18. Change From Screening in Urine Laboratory Tests at Month 6 [ Time Frame: Screening, Month 6 ]
    Change from screening in urine laboratory tests will be summarized over time.


Other Outcome Measures:
  1. Seizure Counts [ Time Frame: Months 1, 2, 3, 6, 9 and 12 ]
    Seizure counts will be summarized over time.

  2. Change From Baseline in Cognitive Assessment at Month 6 and 12 [ Time Frame: Baseline, Month 6 and 12 ]
    Cognitive Assessment will be assessed by the computerized Cogstate Battery test. Number and percentage of subjects with a meaningful decline in cognition (defined as a standardized change of less than -1.65) will be summarized.

  3. Change From Baseline in Child behavior check list (CBCL) at Month 3, 6 and 12 [ Time Frame: Baseline, Month 3, 6 and 12 ]
    The CBCL will include: 1). Preschool version - participants 1.5 to 5 years of age 2). School-age version - participants 6 to 18 years of age. It will measure child internalizing and externalizing behaviors and total problems. Respondents are asked to rate as 0 for "not true of the child," 1 for "somewhat or sometimes true of the child," and 2 for "very true or often true of the child".

  4. Change From Baseline in Vineland score at Month 3, 6 and 12 [ Time Frame: Baseline, Month 3, 6 and 12 ]
    The Vineland Adaptive Behavior Scale, version 2 focuses on behaviors needed to operate in an age-appropriate manner in the individual's environment. It is age-specific and provides an assessment of function in the domains of communication, daily living, socialization, and motor skills, as well as a composite scale.

  5. Suicidalility Behavior [ Time Frame: Baseline, Month 1, 2, 3, 6, 9 and 12 ]
    Suicidalility Behavior will be assessed by Columbia Suicide Severity Rating Scale (C-SSRS), which is a low-burden measure of the spectrum of suicidal ideation and will be administered at every visit, to assess suicidal ideation, intent, and behavior.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   2 Years to 15 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02201251


Contacts
Contact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions: JNJ.CT@sylogent.com

  Show 80 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

Additional Information:
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT02201251     History of Changes
Other Study ID Numbers: CR104425
TOPMATEPY4067 ( Other Identifier: Janssen Research & Development, LLC )
2012-001552-19 ( EudraCT Number )
First Posted: July 28, 2014    Key Record Dates
Last Update Posted: November 15, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Janssen Research & Development, LLC:
Epilepsy
Topiramate
Levetiracetam
Pediatric

Additional relevant MeSH terms:
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Topiramate
Etiracetam
Piracetam
Anticonvulsants
Neuroprotective Agents
Protective Agents
Physiological Effects of Drugs
Anti-Obesity Agents
Nootropic Agents