A dose-comparison trial of topiramate as monotherapy in recently diagnosed partial epilepsy

F. G. Gilliam, F. Veloso, M. A M Bomhof, S. K. Gazda, V. Biton, J. P. Ter Bruggen, W. Neto, C. Bailey, G. Pledger, S. C. Wu, J. Alving, S. Arroyo, R. Arts, R. Ayala, R. Barbano, E. Ben-Menachem, W. Blume, E. Brodtkorb, T. R. Browne, D. ChadwickC. Couch, P. K. Crumrine, M. Dam, P. P. De Deyn, C. Dellaportas, H. Desai, K. R. Edwards, B. Engelsen, R. D. Farran, L. M. Frank, J. French, A. J. Friedman, J. Gelbum, C. L. Harden, C. Hart, O. Henriksen, M. D. Hoffstetter, P. J. Holt, J. F. Hulihan, R. P. Hull, T. Husainy, H. Kang, R. Kern, S. S. Kirzinger, M. A. Lee, R. F. Leroy, J. Licht, J. Mai, R. Michelucci, G. L. Morris, R. Mutani, M. Narus, M. Nieto Barrera, M. Nisman-Safirstein, A. Ogunyemi, J. Pak, P. B. Pennell, S. G. Phillips, N. Pillay, R. E. Ramsay, F. J. Ritter, N. T. Rogers-Neame, W. E. Rosenfeld, J. Schneiderman, R. Singer, N. K. So, B. Soederfeldt, I. N. Soryall, M. Sperling, E. Starreveld, B. J. Steinhoff, S. R G Stodiek, J. T J Tans, A. B. Todorov, C. B. Van Orman, M. Veilleux, O. Waltimo, B. B. Wannamaker, D. Weaver, P. Zagnoni

Research output: Contribution to journalArticle

Abstract

Objective: To evaluate topiramate as monotherapy in adults and children with recently diagnosed, localization-related epilepsy, comparing two dosages of topiramate in a multicenter, randomized, double-blind study. Methods: Adults and children (≥3 years of age) were eligible if the maximum interval since epilepsy diagnosis was 3 years and patients had one to six partial-onset seizures during a 3-month retrospective baseline. At study entry, patients (N = 252) were untreated or receiving one antiepileptic drug for less than 1 month. After randomization to 50 or 500 mg/d topiramate (25 or 200 mg/d if weight ≤ 50 kg), patients remained in the study until 4 months after the last patient was randomized or until patients met seizure-related exit criteria (e.g., had two seizures). The primary efficacy outcome was a univariate analysis of time-to-exit, which was time to second seizure in 96% of patients. Results: The time-to-exit (median, 422 days vs 293 days) favored the higher dose of topiramate, but this difference was not significant. When time-to-exit was analyzed with time-to-first-seizure as a covariate, the difference between dosage groups was significant (p = 0.01), reflecting the higher seizure-free rates (54% vs 39%, p = 0.02) and longer time-to-first-seizure (median 317 days vs 108 days; p = 0.06) in patients receiving 200 or 500 mg/d topiramate. Higher plasma concentration was associated with increased time-to-first seizure (p <0.01). Dose-related adverse events included paresthesia, weight loss, diarrhea, and hypoesthesia. Conclusions: Although the primary efficacy analysis was negative, time-to-exit analyses that included time-to-first-seizure as a covariate, between-group differences in seizure-free rates, and longer time-to-first-seizure with higher serum concentration provide evidence that topiramate is effective as monotherapy in patients with localization-related epilepsy.

Original languageEnglish
Pages (from-to)196-202
Number of pages7
JournalNeurology
Volume60
Issue number2
Publication statusPublished - Jan 28 2003

Fingerprint

Partial Epilepsy
Seizures
topiramate
Hypesthesia
Paresthesia
Random Allocation
Double-Blind Method
Anticonvulsants
Weight Loss
Diarrhea
Epilepsy
Weights and Measures

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Gilliam, F. G., Veloso, F., Bomhof, M. A. M., Gazda, S. K., Biton, V., Ter Bruggen, J. P., ... Zagnoni, P. (2003). A dose-comparison trial of topiramate as monotherapy in recently diagnosed partial epilepsy. Neurology, 60(2), 196-202.

A dose-comparison trial of topiramate as monotherapy in recently diagnosed partial epilepsy. / Gilliam, F. G.; Veloso, F.; Bomhof, M. A M; Gazda, S. K.; Biton, V.; Ter Bruggen, J. P.; Neto, W.; Bailey, C.; Pledger, G.; Wu, S. C.; Alving, J.; Arroyo, S.; Arts, R.; Ayala, R.; Barbano, R.; Ben-Menachem, E.; Blume, W.; Brodtkorb, E.; Browne, T. R.; Chadwick, D.; Couch, C.; Crumrine, P. K.; Dam, M.; De Deyn, P. P.; Dellaportas, C.; Desai, H.; Edwards, K. R.; Engelsen, B.; Farran, R. D.; Frank, L. M.; French, J.; Friedman, A. J.; Gelbum, J.; Harden, C. L.; Hart, C.; Henriksen, O.; Hoffstetter, M. D.; Holt, P. J.; Hulihan, J. F.; Hull, R. P.; Husainy, T.; Kang, H.; Kern, R.; Kirzinger, S. S.; Lee, M. A.; Leroy, R. F.; Licht, J.; Mai, J.; Michelucci, R.; Morris, G. L.; Mutani, R.; Narus, M.; Nieto Barrera, M.; Nisman-Safirstein, M.; Ogunyemi, A.; Pak, J.; Pennell, P. B.; Phillips, S. G.; Pillay, N.; Ramsay, R. E.; Ritter, F. J.; Rogers-Neame, N. T.; Rosenfeld, W. E.; Schneiderman, J.; Singer, R.; So, N. K.; Soederfeldt, B.; Soryall, I. N.; Sperling, M.; Starreveld, E.; Steinhoff, B. J.; Stodiek, S. R G; Tans, J. T J; Todorov, A. B.; Van Orman, C. B.; Veilleux, M.; Waltimo, O.; Wannamaker, B. B.; Weaver, D.; Zagnoni, P.

In: Neurology, Vol. 60, No. 2, 28.01.2003, p. 196-202.

Research output: Contribution to journalArticle

Gilliam, FG, Veloso, F, Bomhof, MAM, Gazda, SK, Biton, V, Ter Bruggen, JP, Neto, W, Bailey, C, Pledger, G, Wu, SC, Alving, J, Arroyo, S, Arts, R, Ayala, R, Barbano, R, Ben-Menachem, E, Blume, W, Brodtkorb, E, Browne, TR, Chadwick, D, Couch, C, Crumrine, PK, Dam, M, De Deyn, PP, Dellaportas, C, Desai, H, Edwards, KR, Engelsen, B, Farran, RD, Frank, LM, French, J, Friedman, AJ, Gelbum, J, Harden, CL, Hart, C, Henriksen, O, Hoffstetter, MD, Holt, PJ, Hulihan, JF, Hull, RP, Husainy, T, Kang, H, Kern, R, Kirzinger, SS, Lee, MA, Leroy, RF, Licht, J, Mai, J, Michelucci, R, Morris, GL, Mutani, R, Narus, M, Nieto Barrera, M, Nisman-Safirstein, M, Ogunyemi, A, Pak, J, Pennell, PB, Phillips, SG, Pillay, N, Ramsay, RE, Ritter, FJ, Rogers-Neame, NT, Rosenfeld, WE, Schneiderman, J, Singer, R, So, NK, Soederfeldt, B, Soryall, IN, Sperling, M, Starreveld, E, Steinhoff, BJ, Stodiek, SRG, Tans, JTJ, Todorov, AB, Van Orman, CB, Veilleux, M, Waltimo, O, Wannamaker, BB, Weaver, D & Zagnoni, P 2003, 'A dose-comparison trial of topiramate as monotherapy in recently diagnosed partial epilepsy', Neurology, vol. 60, no. 2, pp. 196-202.
Gilliam FG, Veloso F, Bomhof MAM, Gazda SK, Biton V, Ter Bruggen JP et al. A dose-comparison trial of topiramate as monotherapy in recently diagnosed partial epilepsy. Neurology. 2003 Jan 28;60(2):196-202.
Gilliam, F. G. ; Veloso, F. ; Bomhof, M. A M ; Gazda, S. K. ; Biton, V. ; Ter Bruggen, J. P. ; Neto, W. ; Bailey, C. ; Pledger, G. ; Wu, S. C. ; Alving, J. ; Arroyo, S. ; Arts, R. ; Ayala, R. ; Barbano, R. ; Ben-Menachem, E. ; Blume, W. ; Brodtkorb, E. ; Browne, T. R. ; Chadwick, D. ; Couch, C. ; Crumrine, P. K. ; Dam, M. ; De Deyn, P. P. ; Dellaportas, C. ; Desai, H. ; Edwards, K. R. ; Engelsen, B. ; Farran, R. D. ; Frank, L. M. ; French, J. ; Friedman, A. J. ; Gelbum, J. ; Harden, C. L. ; Hart, C. ; Henriksen, O. ; Hoffstetter, M. D. ; Holt, P. J. ; Hulihan, J. F. ; Hull, R. P. ; Husainy, T. ; Kang, H. ; Kern, R. ; Kirzinger, S. S. ; Lee, M. A. ; Leroy, R. F. ; Licht, J. ; Mai, J. ; Michelucci, R. ; Morris, G. L. ; Mutani, R. ; Narus, M. ; Nieto Barrera, M. ; Nisman-Safirstein, M. ; Ogunyemi, A. ; Pak, J. ; Pennell, P. B. ; Phillips, S. G. ; Pillay, N. ; Ramsay, R. E. ; Ritter, F. J. ; Rogers-Neame, N. T. ; Rosenfeld, W. E. ; Schneiderman, J. ; Singer, R. ; So, N. K. ; Soederfeldt, B. ; Soryall, I. N. ; Sperling, M. ; Starreveld, E. ; Steinhoff, B. J. ; Stodiek, S. R G ; Tans, J. T J ; Todorov, A. B. ; Van Orman, C. B. ; Veilleux, M. ; Waltimo, O. ; Wannamaker, B. B. ; Weaver, D. ; Zagnoni, P. / A dose-comparison trial of topiramate as monotherapy in recently diagnosed partial epilepsy. In: Neurology. 2003 ; Vol. 60, No. 2. pp. 196-202.
@article{ab448fcc610e4a12bf059206fa561216,
title = "A dose-comparison trial of topiramate as monotherapy in recently diagnosed partial epilepsy",
abstract = "Objective: To evaluate topiramate as monotherapy in adults and children with recently diagnosed, localization-related epilepsy, comparing two dosages of topiramate in a multicenter, randomized, double-blind study. Methods: Adults and children (≥3 years of age) were eligible if the maximum interval since epilepsy diagnosis was 3 years and patients had one to six partial-onset seizures during a 3-month retrospective baseline. At study entry, patients (N = 252) were untreated or receiving one antiepileptic drug for less than 1 month. After randomization to 50 or 500 mg/d topiramate (25 or 200 mg/d if weight ≤ 50 kg), patients remained in the study until 4 months after the last patient was randomized or until patients met seizure-related exit criteria (e.g., had two seizures). The primary efficacy outcome was a univariate analysis of time-to-exit, which was time to second seizure in 96{\%} of patients. Results: The time-to-exit (median, 422 days vs 293 days) favored the higher dose of topiramate, but this difference was not significant. When time-to-exit was analyzed with time-to-first-seizure as a covariate, the difference between dosage groups was significant (p = 0.01), reflecting the higher seizure-free rates (54{\%} vs 39{\%}, p = 0.02) and longer time-to-first-seizure (median 317 days vs 108 days; p = 0.06) in patients receiving 200 or 500 mg/d topiramate. Higher plasma concentration was associated with increased time-to-first seizure (p <0.01). Dose-related adverse events included paresthesia, weight loss, diarrhea, and hypoesthesia. Conclusions: Although the primary efficacy analysis was negative, time-to-exit analyses that included time-to-first-seizure as a covariate, between-group differences in seizure-free rates, and longer time-to-first-seizure with higher serum concentration provide evidence that topiramate is effective as monotherapy in patients with localization-related epilepsy.",
author = "Gilliam, {F. G.} and F. Veloso and Bomhof, {M. A M} and Gazda, {S. K.} and V. Biton and {Ter Bruggen}, {J. P.} and W. Neto and C. Bailey and G. Pledger and Wu, {S. C.} and J. Alving and S. Arroyo and R. Arts and R. Ayala and R. Barbano and E. Ben-Menachem and W. Blume and E. Brodtkorb and Browne, {T. R.} and D. Chadwick and C. Couch and Crumrine, {P. K.} and M. Dam and {De Deyn}, {P. P.} and C. Dellaportas and H. Desai and Edwards, {K. R.} and B. Engelsen and Farran, {R. D.} and Frank, {L. M.} and J. French and Friedman, {A. J.} and J. Gelbum and Harden, {C. L.} and C. Hart and O. Henriksen and Hoffstetter, {M. D.} and Holt, {P. J.} and Hulihan, {J. F.} and Hull, {R. P.} and T. Husainy and H. Kang and R. Kern and Kirzinger, {S. S.} and Lee, {M. A.} and Leroy, {R. F.} and J. Licht and J. Mai and R. Michelucci and Morris, {G. L.} and R. Mutani and M. Narus and {Nieto Barrera}, M. and M. Nisman-Safirstein and A. Ogunyemi and J. Pak and Pennell, {P. B.} and Phillips, {S. G.} and N. Pillay and Ramsay, {R. E.} and Ritter, {F. J.} and Rogers-Neame, {N. T.} and Rosenfeld, {W. E.} and J. Schneiderman and R. Singer and So, {N. K.} and B. Soederfeldt and Soryall, {I. N.} and M. Sperling and E. Starreveld and Steinhoff, {B. J.} and Stodiek, {S. R G} and Tans, {J. T J} and Todorov, {A. B.} and {Van Orman}, {C. B.} and M. Veilleux and O. Waltimo and Wannamaker, {B. B.} and D. Weaver and P. Zagnoni",
year = "2003",
month = "1",
day = "28",
language = "English",
volume = "60",
pages = "196--202",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - A dose-comparison trial of topiramate as monotherapy in recently diagnosed partial epilepsy

AU - Gilliam, F. G.

AU - Veloso, F.

AU - Bomhof, M. A M

AU - Gazda, S. K.

AU - Biton, V.

AU - Ter Bruggen, J. P.

AU - Neto, W.

AU - Bailey, C.

AU - Pledger, G.

AU - Wu, S. C.

AU - Alving, J.

AU - Arroyo, S.

AU - Arts, R.

AU - Ayala, R.

AU - Barbano, R.

AU - Ben-Menachem, E.

AU - Blume, W.

AU - Brodtkorb, E.

AU - Browne, T. R.

AU - Chadwick, D.

AU - Couch, C.

AU - Crumrine, P. K.

AU - Dam, M.

AU - De Deyn, P. P.

AU - Dellaportas, C.

AU - Desai, H.

AU - Edwards, K. R.

AU - Engelsen, B.

AU - Farran, R. D.

AU - Frank, L. M.

AU - French, J.

AU - Friedman, A. J.

AU - Gelbum, J.

AU - Harden, C. L.

AU - Hart, C.

AU - Henriksen, O.

AU - Hoffstetter, M. D.

AU - Holt, P. J.

AU - Hulihan, J. F.

AU - Hull, R. P.

AU - Husainy, T.

AU - Kang, H.

AU - Kern, R.

AU - Kirzinger, S. S.

AU - Lee, M. A.

AU - Leroy, R. F.

AU - Licht, J.

AU - Mai, J.

AU - Michelucci, R.

AU - Morris, G. L.

AU - Mutani, R.

AU - Narus, M.

AU - Nieto Barrera, M.

AU - Nisman-Safirstein, M.

AU - Ogunyemi, A.

AU - Pak, J.

AU - Pennell, P. B.

AU - Phillips, S. G.

AU - Pillay, N.

AU - Ramsay, R. E.

AU - Ritter, F. J.

AU - Rogers-Neame, N. T.

AU - Rosenfeld, W. E.

AU - Schneiderman, J.

AU - Singer, R.

AU - So, N. K.

AU - Soederfeldt, B.

AU - Soryall, I. N.

AU - Sperling, M.

AU - Starreveld, E.

AU - Steinhoff, B. J.

AU - Stodiek, S. R G

AU - Tans, J. T J

AU - Todorov, A. B.

AU - Van Orman, C. B.

AU - Veilleux, M.

AU - Waltimo, O.

AU - Wannamaker, B. B.

AU - Weaver, D.

AU - Zagnoni, P.

PY - 2003/1/28

Y1 - 2003/1/28

N2 - Objective: To evaluate topiramate as monotherapy in adults and children with recently diagnosed, localization-related epilepsy, comparing two dosages of topiramate in a multicenter, randomized, double-blind study. Methods: Adults and children (≥3 years of age) were eligible if the maximum interval since epilepsy diagnosis was 3 years and patients had one to six partial-onset seizures during a 3-month retrospective baseline. At study entry, patients (N = 252) were untreated or receiving one antiepileptic drug for less than 1 month. After randomization to 50 or 500 mg/d topiramate (25 or 200 mg/d if weight ≤ 50 kg), patients remained in the study until 4 months after the last patient was randomized or until patients met seizure-related exit criteria (e.g., had two seizures). The primary efficacy outcome was a univariate analysis of time-to-exit, which was time to second seizure in 96% of patients. Results: The time-to-exit (median, 422 days vs 293 days) favored the higher dose of topiramate, but this difference was not significant. When time-to-exit was analyzed with time-to-first-seizure as a covariate, the difference between dosage groups was significant (p = 0.01), reflecting the higher seizure-free rates (54% vs 39%, p = 0.02) and longer time-to-first-seizure (median 317 days vs 108 days; p = 0.06) in patients receiving 200 or 500 mg/d topiramate. Higher plasma concentration was associated with increased time-to-first seizure (p <0.01). Dose-related adverse events included paresthesia, weight loss, diarrhea, and hypoesthesia. Conclusions: Although the primary efficacy analysis was negative, time-to-exit analyses that included time-to-first-seizure as a covariate, between-group differences in seizure-free rates, and longer time-to-first-seizure with higher serum concentration provide evidence that topiramate is effective as monotherapy in patients with localization-related epilepsy.

AB - Objective: To evaluate topiramate as monotherapy in adults and children with recently diagnosed, localization-related epilepsy, comparing two dosages of topiramate in a multicenter, randomized, double-blind study. Methods: Adults and children (≥3 years of age) were eligible if the maximum interval since epilepsy diagnosis was 3 years and patients had one to six partial-onset seizures during a 3-month retrospective baseline. At study entry, patients (N = 252) were untreated or receiving one antiepileptic drug for less than 1 month. After randomization to 50 or 500 mg/d topiramate (25 or 200 mg/d if weight ≤ 50 kg), patients remained in the study until 4 months after the last patient was randomized or until patients met seizure-related exit criteria (e.g., had two seizures). The primary efficacy outcome was a univariate analysis of time-to-exit, which was time to second seizure in 96% of patients. Results: The time-to-exit (median, 422 days vs 293 days) favored the higher dose of topiramate, but this difference was not significant. When time-to-exit was analyzed with time-to-first-seizure as a covariate, the difference between dosage groups was significant (p = 0.01), reflecting the higher seizure-free rates (54% vs 39%, p = 0.02) and longer time-to-first-seizure (median 317 days vs 108 days; p = 0.06) in patients receiving 200 or 500 mg/d topiramate. Higher plasma concentration was associated with increased time-to-first seizure (p <0.01). Dose-related adverse events included paresthesia, weight loss, diarrhea, and hypoesthesia. Conclusions: Although the primary efficacy analysis was negative, time-to-exit analyses that included time-to-first-seizure as a covariate, between-group differences in seizure-free rates, and longer time-to-first-seizure with higher serum concentration provide evidence that topiramate is effective as monotherapy in patients with localization-related epilepsy.

UR - http://www.scopus.com/inward/record.url?scp=0037469199&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037469199&partnerID=8YFLogxK

M3 - Article

C2 - 12552030

AN - SCOPUS:0037469199

VL - 60

SP - 196

EP - 202

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 2

ER -