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A Multicenter, Randomized, Double-Blind, Controlled Dose Finding Study of NGX-4010, a High-Concentration Capsaicin Patch, for the Treatment of Postherpetic Neuralgia

      Abstract

      Postherpetic neuralgia (PHN) is a painful complication of acute herpes zoster. This multicenter, double-blind, controlled study randomized 299 PHN patients to receive either NGX-4010, a high-concentration capsaicin (8%) patch, or a low-concentration capsaicin (0.04%) control patch for 30, 60, or 90 minutes. The mean percent reductions in NPRS score from baseline to weeks 2 through 8 were significantly greater in the total NGX-4010 group (26.5%, P = .0286) and the 90-minute NGX-4010 group (27.8%, P = .0438) compared to the pooled control group (17.3%). After review of the data suggested a difference between genders in reporting of pain scores and a higher proportion of males (61%) in the 60-minute NGX-4010 group, post hoc gender-stratified analyses were performed and showed that the 60-minute NGX-4010 group also had a significantly larger mean percent reduction in average pain scores (28.0%, P = .0331). Pain reduction in the 30-minute NGX-4010 group, although similar in magnitude to the other doses, was not significantly different from control in either of these analyses. Similar results were observed during weeks 2 through 12. Most treatment-emergent adverse events were application-site specific, transient and mostly mild to moderate in severity.

      Perspective

      This article reports the safety and efficacy of NGX-4010 applied for 3 different durations (30, 60, or 90 minutes) in patients with PHN. The results identified the 60-minute duration as the dose to be evaluated in subsequent studies and identified a gender effect on reported changes in pain.

      Key words

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      References

        • Backonja M.M.
        • Dunteman E.
        • Irving G.A.
        • Blonsky E.R.
        • Vanhove G.F.
        • Lu S.-P.
        • Tobias J.K.
        One 60-minute application of a high-concentration capsaicin patch (NGX-4010) significantly reduced pain for up to 3 months in patients with postherpetic neuralgia: Results from a randomized, double-blind, controlled phase 3 study.
        Neurology. 2008; 70: A162-A163
        • Backonja M.
        • Irving G.
        • Argoff C.
        Rational Multidrug Therapy in the Treatment of Neuropathic Pain.
        Curr Pain Headache Rep. 2006; 10: 34-38
        • Backonja M.
        • Wallace M.S.
        • Blonsky E.R.
        • Cutler B.J.
        • Malan Jr., P.
        • Rauck R.
        • Tobias J.
        • NGX-4010 C116 Study Group
        NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia: a randomised, double-blind study.
        Lancet Neurol. 2008; 7: 1106-1112
        • Baron R.
        • Wasner G.
        Prevention and treatment of postherpetic neuralgia.
        Lancet. 2006; 367: 186-188
        • Bernstein J.E.
        • Korman N.J.
        • Bickers D.R.
        • Dahl M.V.
        • Millikan L.E.
        Topical capsaicin treatment of chronic postherpetic neuralgia.
        J Am Acad Dermatol. 1989; 21: 265-270
        • Bley K.R.
        Recent developments in transient receptor potential vanilloid receptor 1 agonist-based therapies.
        Expert Opin Investig Drugs. 2004; 13: 1445-1456
        • Cleeland C.S.
        • Ryan K.M.
        Pain assessment: global use of the Brief Pain Inventory.
        Ann Acad Med Singapore. 1994; 23: 129-138
        • Cortright D.N.
        • Szallasi A.
        Biochemical pharmacology of the vanilloid receptor TRPV1. An update.
        Eur J Biochem. 2004; 271: 1814-1819
        • Craft R.M.
        Sex differences in opioid analgesia: ”from mouse to man”.
        Clin J Pain. 2003; 19: 175-186
        • Dahan A.
        • Kest B.
        • Waxman A.R.
        • Sarton E.
        Sex-specific responses to opiates: animal and human studies.
        Anesth Analg. 2008; 107: 83-95
        • Dworkin R.H.
        • O'Connor A.B.
        • Backonja M.
        • Farrar J.T.
        • Finnerup N.B.
        • Jensen T.S.
        • Kalso E.A.
        • Loeser J.D.
        • Miaskowski C.
        • Nurmikko T.J.
        • Portenoy R.K.
        • Rice A.S.
        • Stacey B.R.
        • Treede R.D.
        • Turk D.C.
        • Wallace M.S.
        Pharmacologic management of neuropathic pain: evidence-based recommendations.
        Pain. 2007; 132: 237-251
        • Farrar J.T.
        • Young Jr., J.P.
        • LaMoreaux L.
        • Werth J.L.
        • Poole R.M.
        Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale.
        Pain. 2001; 94: 149-158
        • Fillingim R.B.
        • Gear R.W.
        Sex differences in opioid analgesia: clinical and experimental findings.
        Eur J Pain. 2004; 8: 413-425
        • Fillingim R.B.
        • King C.D.
        • Ribeiro-Dasilva M.C.
        • Rahim-Williams B.
        • Riley III, J.L.
        Sex, gender, and pain: a review of recent clinical and experimental findings.
        J Pain. 2009; 10: 447-485
        • Finnerup N.B.
        • Otto M.
        • McQuay H.J.
        • Jensen T.S.
        • Sindrup S.H.
        Algorithm for neuropathic pain treatment: an evidence based proposal.
        Pain. 2005; 118: 289-305
        • Hall G.C.
        • Carroll D.
        • McQuay H.J.
        Primary care incidence and treatment of four neuropathic pain conditions: A descriptive study, 2002–2005.
        BMC Fam Pract. 2008; 9: 26
        • Irving G.A.
        • Backonja M.M.
        • Blonsky E.R.
        • Rauck R.
        • Gazda S.K.
        • Lu S.-P.
        • Vanhove G.F.
        • Tobias J.K.
        NGX-4010, a high-concentration capsaicin patch, administered alone or in combination with systemic neuropathic pain medications, reduces pain in patients with postherpetic neuralgia.
        J Pain. 2009; 10: S57
        • Jackson K.C.
        II: Pharmacotherapy for neuropathic pain.
        Pain Pract. 2006; 6: 27-33
        • Johnson R.W.
        • Dworkin R.H.
        Treatment of herpes zoster and postherpetic neuralgia.
        BMJ. 2003; 326: 748-750
        • Lauria G.
        • Morbin M.
        • Lombardi R.
        • Capobianco R.
        • Camozzi F.
        • Pareyson D.
        • Manconi M.
        • Geppetti P.
        Expression of capsaicin receptor immunoreactivity in human peripheral nervous system and in painful neuropathies.
        J Peripher Nerv Syst. 2006; 11: 262-271
        • Melzack R.
        The short-form McGill Pain Questionnaire.
        Pain. 1987; 30: 191-197
        • Miaskowski C.
        • Gear R.W.
        • Levine J.D.
        Sex-related differences in analgesic responses.
        in: Fillingim R. Sex, Gender and Pain. IASP Press, Seattle, WA2000: 209-230
        • Peikert A.
        • Hentrich M.
        • Ochs G.
        Topical 0.025% capsaicin in chronic post-herpetic neuralgia: efficacy, predictors of response and long-term course.
        J Neurol. 1991; 238: 452-456
        • Petersen K.L.
        • Fields H.L.
        • Brennum J.
        • Sandroni P.
        • Rowbotham M.C.
        Capsaicin evoked pain and allodynia in post-herpetic neuralgia.
        Pain. 2000; 88: 125-133
        • Robinson M.E.
        • Riley III, J.L.
        • Brown F.F.
        • Gremillion H.
        Sex differences in response to cutaneous anesthesia: a double blind randomized study.
        Pain. 1998; 77: 143-149
        • Rowbotham M.C.
        • Petersen K.L.
        Zoster-associated pain and neural dysfunction.
        Pain. 2001; 93: 1-5
        • Schmader K.E.
        Epidemiology and impact on quality of life of postherpetic neuralgia and painful diabetic neuropathy.
        Clin J Pain. 2002; 18: 350-354
        • Schneider L.S.
        • Clark C.M.
        • Doody R.
        • Ferris S.H.
        • Morris J.C.
        • Raman R.
        • Reisberg B.
        • Schmitt F.A.
        ADCS Prevention Instrument Project: ADCS-clinicians' global impression of change scales (ADCS-CGIC), self-rated and study partner-rated versions.
        Alzheimer Dis Assoc Disord. 2006; 20: S124-S138
        • Sindrup S.H.
        • Jensen T.S.
        Efficacy of pharmacological treatments of neuropathic pain: an update and effect related to mechanism of drug action.
        Pain. 1999; 83: 389-400
        • Szallasi A.
        • Blumberg P.M.
        Vanilloid (capsaicin) receptors and mechanisms.
        Pharmacol Rev. 1999; 51: 159-212
        • Tominaga M.
        Nociception and TRP channels.
        Handb Exp Pharmacol. 2007; 179: 489-505
      1. US Food and Drug Administration Center for Drug Evaluation and Research. Guidance for industry: skin irritation and sensitization testing of generic transdermal drug products. Washington, DC. US Department of Health and Human Services, Food and Drug Administration Center for Drug Evaluation and Research, 1999. Available at: http://www.fda.gov/ohrms/dockets/98fr/990236Gd.pdf#search=%22HillTop%20Research%2C%20Inc.%20dermal%20irritation%22.

        • Walker J.S.
        • Carmody J.J.
        Experimental pain in healthy human subjects: Gender differences in nociception and in response to ibuprofen.
        Anesth Analg. 1998; 86: 1257-1262
        • Watson C.P.
        A new treatment for postherpetic neuralgia.
        N Engl J Med. 2000; 343: 1563-1565