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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02201251




Registration number
NCT02201251
Ethics application status
Date submitted
24/07/2014
Date registered
28/07/2014
Date last updated
17/05/2021

Titles & IDs
Public title
A Study to Investigate the Safety of the Drugs Topiramate and Levetiracetam in Treating Children Recently Diagnosed With Epilepsy
Scientific 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
Secondary ID [1] 0 0
TOPMATEPY4067
Secondary ID [2] 0 0
CR104425
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Epilepsy 0 0
Condition category
Condition code
Neurological 0 0 0 0
Epilepsy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Topiramate
Treatment: Drugs - Levetiracetam

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.

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).


Treatment: Drugs: 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.

Treatment: Drugs: 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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline up to Month 1
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
Baseline up to Month 3
Primary outcome [3] 0 0
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.
Timepoint [3] 0 0
Baseline up to Month 6
Primary outcome [4] 0 0
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.
Timepoint [4] 0 0
Baseline up to Month 9
Primary outcome [5] 0 0
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.
Timepoint [5] 0 0
Baseline up to Month 12
Primary outcome [6] 0 0
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.
Timepoint [6] 0 0
Baseline up to Month 1
Primary outcome [7] 0 0
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.
Timepoint [7] 0 0
Baseline up to Month 3
Primary outcome [8] 0 0
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.
Timepoint [8] 0 0
Baseline up to Month 6
Primary outcome [9] 0 0
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.
Timepoint [9] 0 0
Baseline up to Month 9
Primary outcome [10] 0 0
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.
Timepoint [10] 0 0
Baseline up to Month 12
Primary outcome [11] 0 0
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.
Timepoint [11] 0 0
Baseline up to Month 6
Primary outcome [12] 0 0
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.
Timepoint [12] 0 0
Baseline up to Month 12
Primary outcome [13] 0 0
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.
Timepoint [13] 0 0
Baseline up to Month 6
Primary outcome [14] 0 0
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.
Timepoint [14] 0 0
Baseline up to Month 12
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Up to Day 390
Secondary outcome [2] 0 0
Percentage of Participants With Kidney Stones - Percentage of participants with kidney stones were reported.
Timepoint [2] 0 0
Up to Day 390

Eligibility
Key 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
Minimum age
2 Years
Maximum age
15 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Health Services Research
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Queensland
Recruitment postcode(s) [1] 0 0
- Queensland
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Kentucky
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Oregon
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Argentina
State/province [8] 0 0
Buenos Aires
Country [9] 0 0
Argentina
State/province [9] 0 0
Cordoba
Country [10] 0 0
Austria
State/province [10] 0 0
Graz
Country [11] 0 0
Belgium
State/province [11] 0 0
Leuven
Country [12] 0 0
Belgium
State/province [12] 0 0
Namur
Country [13] 0 0
Canada
State/province [13] 0 0
Saskatchewan
Country [14] 0 0
France
State/province [14] 0 0
Brest
Country [15] 0 0
France
State/province [15] 0 0
Bron
Country [16] 0 0
France
State/province [16] 0 0
Paris
Country [17] 0 0
France
State/province [17] 0 0
Toulouse
Country [18] 0 0
Germany
State/province [18] 0 0
Munchen
Country [19] 0 0
Germany
State/province [19] 0 0
Tübingen
Country [20] 0 0
Hungary
State/province [20] 0 0
Balassagyarmat
Country [21] 0 0
Hungary
State/province [21] 0 0
Budapest N/a
Country [22] 0 0
Hungary
State/province [22] 0 0
Debrecen
Country [23] 0 0
Hungary
State/province [23] 0 0
Veszprém
Country [24] 0 0
Philippines
State/province [24] 0 0
Cebu
Country [25] 0 0
Philippines
State/province [25] 0 0
Manila
Country [26] 0 0
Poland
State/province [26] 0 0
Krakow
Country [27] 0 0
Poland
State/province [27] 0 0
Poznan
Country [28] 0 0
Poland
State/province [28] 0 0
Warsaw
Country [29] 0 0
Poland
State/province [29] 0 0
Warszawa
Country [30] 0 0
Russian Federation
State/province [30] 0 0
Saint Petersburg
Country [31] 0 0
Russian Federation
State/province [31] 0 0
Ulyanovsk
Country [32] 0 0
South Africa
State/province [32] 0 0
Durban
Country [33] 0 0
Taiwan
State/province [33] 0 0
Kaohsiung
Country [34] 0 0
Taiwan
State/province [34] 0 0
New Taipei City
Country [35] 0 0
Taiwan
State/province [35] 0 0
Taichung
Country [36] 0 0
Taiwan
State/province [36] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Janssen Research & Development, LLC
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02201251
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Janssen Research & Development, LLC Clinical Trial
Address 0 0
Janssen Research & Development, LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications