Safety and effectiveness of topiramate for the management of painful diabetic peripheral neuropathy in an open-label extension study

Peter D. Donofrio, Philip Raskin, Norman R. Rosenthal, David J. Hewitt, Donna M. Jordan, Jim Xiang, Aaron I. Vinik

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Objective: The aim of this study was to further assess the long-term safety and effectiveness of open-label topiramate therapy in subjects with moderately to severely painful diabetic peripheral neuropathy (DPN). Methods: Adults aged 18 to 75 years received open-label topiramate (25-600 mg/d for 26 weeks) in an extension of a previously published randomized, double-blind trial comparing topiramate with placebo. Safety analyses included adverse event (AE) reports and clinical laboratory tests. Metabolic end points included body weight and glycosylated hemoglobin (HbA1c). Effectiveness analyses included a 100-mm pain visual analog (PVA) scale, worst and current pain severity, and sleep disruption. Results: Two hundred five subjects participated in this open-label extension study (118 formerly treated with topiramate and 87 who formerly received placebo). The groups did not differ in baseline demographics or disease characteristics. One hundred twenty-four (60.5%) subjects (68.6% of former topiramate recipients and 49.4% of former placebo recipients) completed the extension study; the most common reason for discontinuation was an AE (27.3% of subjects). AEs among subjects who received <1 dose of topiramate (n = 298) included upper respiratory tract infection (16.1%), anorexia (15.1%), diarrhea (12.8%), nausea (12.8%), paresthesia (10.7%), and headache (10.1%). Baseline pain scores were lower in those formerly treated with topiramate (n = 117) than in the former placebo group (n = 86) (PVA: 43.3 vs 52.5, P = 0.014; worst pain: 1.9 vs 2.5, P < 0.001; current pain: 1.6 vs 1.9, P = 0.026; sleep disruption: 3.6 vs 4.6, P = 0.021). At the final visit, PVA, current pain, and sleep disruption scores were not significantly different between the former topiramate and former placebo groups, but worst pain differed significantly (1.4 vs 1.8; P = 0.025). Mean weight loss from the start of topiramate therapy was 5.2 and 5.3 kg in the former topiramate and former placebo groups, respectively (P < 0.001 vs baseline). Mean HbA1c values before and after topiramate treatment were 7.7% and 7.4%, respectively, in the former topiramate group (P = 0.004 vs baseline), and 7.6% and 7.1%, respectively, in the former placebo group (P < 0.001 vs baseline). Conclusion: Although 39.5% of subjects discontinued, most often due to AEs, the results of this 26-week, open-label extension study with topiramate (up to 600 mg/d) in subjects with moderately to severely painful DPN suggest that pain relief was effective and durable.

Original languageEnglish (US)
Pages (from-to)1420-1431
Number of pages12
JournalClinical Therapeutics
Volume27
Issue number9
DOIs
StatePublished - Sep 2005

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Diabetic Neuropathies
Peripheral Nervous System Diseases
Safety
Pain
Placebos
Sleep
topiramate
Paresthesia
Glycosylated Hemoglobin A
Anorexia
Pain Measurement
Respiratory Tract Infections
Nausea
Headache
Weight Loss
Diarrhea
Therapeutics

Keywords

  • Adverse effects
  • Body weight
  • Pain
  • Painful diabetic neuropathy
  • Topiramate

ASJC Scopus subject areas

  • Pharmacology

Cite this

Safety and effectiveness of topiramate for the management of painful diabetic peripheral neuropathy in an open-label extension study. / Donofrio, Peter D.; Raskin, Philip; Rosenthal, Norman R.; Hewitt, David J.; Jordan, Donna M.; Xiang, Jim; Vinik, Aaron I.

In: Clinical Therapeutics, Vol. 27, No. 9, 09.2005, p. 1420-1431.

Research output: Contribution to journalArticle

Donofrio, Peter D. ; Raskin, Philip ; Rosenthal, Norman R. ; Hewitt, David J. ; Jordan, Donna M. ; Xiang, Jim ; Vinik, Aaron I. / Safety and effectiveness of topiramate for the management of painful diabetic peripheral neuropathy in an open-label extension study. In: Clinical Therapeutics. 2005 ; Vol. 27, No. 9. pp. 1420-1431.
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abstract = "Objective: The aim of this study was to further assess the long-term safety and effectiveness of open-label topiramate therapy in subjects with moderately to severely painful diabetic peripheral neuropathy (DPN). Methods: Adults aged 18 to 75 years received open-label topiramate (25-600 mg/d for 26 weeks) in an extension of a previously published randomized, double-blind trial comparing topiramate with placebo. Safety analyses included adverse event (AE) reports and clinical laboratory tests. Metabolic end points included body weight and glycosylated hemoglobin (HbA1c). Effectiveness analyses included a 100-mm pain visual analog (PVA) scale, worst and current pain severity, and sleep disruption. Results: Two hundred five subjects participated in this open-label extension study (118 formerly treated with topiramate and 87 who formerly received placebo). The groups did not differ in baseline demographics or disease characteristics. One hundred twenty-four (60.5{\%}) subjects (68.6{\%} of former topiramate recipients and 49.4{\%} of former placebo recipients) completed the extension study; the most common reason for discontinuation was an AE (27.3{\%} of subjects). AEs among subjects who received <1 dose of topiramate (n = 298) included upper respiratory tract infection (16.1{\%}), anorexia (15.1{\%}), diarrhea (12.8{\%}), nausea (12.8{\%}), paresthesia (10.7{\%}), and headache (10.1{\%}). Baseline pain scores were lower in those formerly treated with topiramate (n = 117) than in the former placebo group (n = 86) (PVA: 43.3 vs 52.5, P = 0.014; worst pain: 1.9 vs 2.5, P < 0.001; current pain: 1.6 vs 1.9, P = 0.026; sleep disruption: 3.6 vs 4.6, P = 0.021). At the final visit, PVA, current pain, and sleep disruption scores were not significantly different between the former topiramate and former placebo groups, but worst pain differed significantly (1.4 vs 1.8; P = 0.025). Mean weight loss from the start of topiramate therapy was 5.2 and 5.3 kg in the former topiramate and former placebo groups, respectively (P < 0.001 vs baseline). Mean HbA1c values before and after topiramate treatment were 7.7{\%} and 7.4{\%}, respectively, in the former topiramate group (P = 0.004 vs baseline), and 7.6{\%} and 7.1{\%}, respectively, in the former placebo group (P < 0.001 vs baseline). Conclusion: Although 39.5{\%} of subjects discontinued, most often due to AEs, the results of this 26-week, open-label extension study with topiramate (up to 600 mg/d) in subjects with moderately to severely painful DPN suggest that pain relief was effective and durable.",
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T1 - Safety and effectiveness of topiramate for the management of painful diabetic peripheral neuropathy in an open-label extension study

AU - Donofrio, Peter D.

AU - Raskin, Philip

AU - Rosenthal, Norman R.

AU - Hewitt, David J.

AU - Jordan, Donna M.

AU - Xiang, Jim

AU - Vinik, Aaron I.

PY - 2005/9

Y1 - 2005/9

N2 - Objective: The aim of this study was to further assess the long-term safety and effectiveness of open-label topiramate therapy in subjects with moderately to severely painful diabetic peripheral neuropathy (DPN). Methods: Adults aged 18 to 75 years received open-label topiramate (25-600 mg/d for 26 weeks) in an extension of a previously published randomized, double-blind trial comparing topiramate with placebo. Safety analyses included adverse event (AE) reports and clinical laboratory tests. Metabolic end points included body weight and glycosylated hemoglobin (HbA1c). Effectiveness analyses included a 100-mm pain visual analog (PVA) scale, worst and current pain severity, and sleep disruption. Results: Two hundred five subjects participated in this open-label extension study (118 formerly treated with topiramate and 87 who formerly received placebo). The groups did not differ in baseline demographics or disease characteristics. One hundred twenty-four (60.5%) subjects (68.6% of former topiramate recipients and 49.4% of former placebo recipients) completed the extension study; the most common reason for discontinuation was an AE (27.3% of subjects). AEs among subjects who received <1 dose of topiramate (n = 298) included upper respiratory tract infection (16.1%), anorexia (15.1%), diarrhea (12.8%), nausea (12.8%), paresthesia (10.7%), and headache (10.1%). Baseline pain scores were lower in those formerly treated with topiramate (n = 117) than in the former placebo group (n = 86) (PVA: 43.3 vs 52.5, P = 0.014; worst pain: 1.9 vs 2.5, P < 0.001; current pain: 1.6 vs 1.9, P = 0.026; sleep disruption: 3.6 vs 4.6, P = 0.021). At the final visit, PVA, current pain, and sleep disruption scores were not significantly different between the former topiramate and former placebo groups, but worst pain differed significantly (1.4 vs 1.8; P = 0.025). Mean weight loss from the start of topiramate therapy was 5.2 and 5.3 kg in the former topiramate and former placebo groups, respectively (P < 0.001 vs baseline). Mean HbA1c values before and after topiramate treatment were 7.7% and 7.4%, respectively, in the former topiramate group (P = 0.004 vs baseline), and 7.6% and 7.1%, respectively, in the former placebo group (P < 0.001 vs baseline). Conclusion: Although 39.5% of subjects discontinued, most often due to AEs, the results of this 26-week, open-label extension study with topiramate (up to 600 mg/d) in subjects with moderately to severely painful DPN suggest that pain relief was effective and durable.

AB - Objective: The aim of this study was to further assess the long-term safety and effectiveness of open-label topiramate therapy in subjects with moderately to severely painful diabetic peripheral neuropathy (DPN). Methods: Adults aged 18 to 75 years received open-label topiramate (25-600 mg/d for 26 weeks) in an extension of a previously published randomized, double-blind trial comparing topiramate with placebo. Safety analyses included adverse event (AE) reports and clinical laboratory tests. Metabolic end points included body weight and glycosylated hemoglobin (HbA1c). Effectiveness analyses included a 100-mm pain visual analog (PVA) scale, worst and current pain severity, and sleep disruption. Results: Two hundred five subjects participated in this open-label extension study (118 formerly treated with topiramate and 87 who formerly received placebo). The groups did not differ in baseline demographics or disease characteristics. One hundred twenty-four (60.5%) subjects (68.6% of former topiramate recipients and 49.4% of former placebo recipients) completed the extension study; the most common reason for discontinuation was an AE (27.3% of subjects). AEs among subjects who received <1 dose of topiramate (n = 298) included upper respiratory tract infection (16.1%), anorexia (15.1%), diarrhea (12.8%), nausea (12.8%), paresthesia (10.7%), and headache (10.1%). Baseline pain scores were lower in those formerly treated with topiramate (n = 117) than in the former placebo group (n = 86) (PVA: 43.3 vs 52.5, P = 0.014; worst pain: 1.9 vs 2.5, P < 0.001; current pain: 1.6 vs 1.9, P = 0.026; sleep disruption: 3.6 vs 4.6, P = 0.021). At the final visit, PVA, current pain, and sleep disruption scores were not significantly different between the former topiramate and former placebo groups, but worst pain differed significantly (1.4 vs 1.8; P = 0.025). Mean weight loss from the start of topiramate therapy was 5.2 and 5.3 kg in the former topiramate and former placebo groups, respectively (P < 0.001 vs baseline). Mean HbA1c values before and after topiramate treatment were 7.7% and 7.4%, respectively, in the former topiramate group (P = 0.004 vs baseline), and 7.6% and 7.1%, respectively, in the former placebo group (P < 0.001 vs baseline). Conclusion: Although 39.5% of subjects discontinued, most often due to AEs, the results of this 26-week, open-label extension study with topiramate (up to 600 mg/d) in subjects with moderately to severely painful DPN suggest that pain relief was effective and durable.

KW - Adverse effects

KW - Body weight

KW - Pain

KW - Painful diabetic neuropathy

KW - Topiramate

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