BACKGROUND: This 52-week study evaluated the long-term safety and tolerability of capsaicin 8% w/w (179 mg) patch repeat treatment plus standard of care (SOC) versus SOC alone in painful diabetic peripheral neuropathy (PDPN). METHODS: Phase 3, multinational, open-label, randomised, controlled, 52-week safety study, conducted in Europe. Patients were randomised to capsaicin 8% patch repeat treatment (30 or 60 min; 1-7 treatments with ≥ 8-week intervals) to painful areas of the feet plus SOC, or SOC alone. The primary objective was the safety of capsaicin 8% patch repeat treatment (30 min and 60 min applications) plus SOC versus SOC alone over 52 weeks, assessed by changes in Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) total score from baseline to end of study (EOS). Secondary safety endpoints included Utah Early Neuropathy Scale (UENS) assessments and standardised testing of sensory perception and reflex function. RESULTS: Overall, 468 patients were randomised (30 min plus SOC, n = 156; 60 min plus SOC, n = 157; SOC alone, n = 155). By EoS, mean changes in Norfolk QOL-DN total score from baseline [estimated mean difference versus SOC alone; 90% CI for difference] were: 30 min plus SOC, -27.6% [-20.9; -31.7, -10.1]; 60 min plus SOC, -32.8% [-26.1; -36.8, -15.4]; SOC alone, -6.7%. Mean changes [difference versus SOC alone] in UENS total score by EoS versus baseline were: 30 min plus SOC, -2.1 [-0.9; -1.8, 0.1]; 60 min plus SOC, -3.0 [-1.7; -2.7, -0.8]; SOC alone, -1.2. No detrimental deterioration was observed in any of the Norfolk or UENS subscales by EoS with capsaicin. Also, no worsening in sensory perception testing of sharp, warm, cold and vibration stimuli was found with capsaicin by EoS. Capsaicin treatment was well tolerated and the most frequent treatment-emergent adverse events were application site pain (30 min, 28.2%; 60 min, 29.3%), burning sensation (30 min, 9.0%; 60 min, 9.6%) and application site erythema (30 min, 7.7%; 60 min, 8.9%). CONCLUSION: In patients with PDPN, capsaicin 8% patch repeat treatment plus SOC over 52 weeks was well tolerated with no negative functional or neurological effects compared with SOC alone. TRIAL REGISTRATION: ClinicalTrials.gov registration: NCT01478607 . Date of registration November 21, 2011; retrospectively registered.

Analgesic Solutions Natick MA USA

Astellas Pharma Europe B 5 Leiden The Netherlands

Eastern Virginia Medical School Strelitz Diabetes Center 855 W Brambleton Avenue Room 2018 Norfolk VA 23510 USA

Hôpital Hôtel Dieu Paris Descartes University Paris France

Hospital Rio Hortega Valladolid Spain

INC Research Camberley UK

Tufts University School of Medicine Boston MA USA

Vestra Clinics Dedicated Research Clinics Rychnov nad Kneznou Czech Republic

Zobrazit více v PubMed

Jensen MP, Chodroff MJ, Dworkin RH, et al. The impact of neuropathic pain on health-related quality of life: review and implications. Neurology. 2007;68:1178–82. doi: 10.1212/01.wnl.0000259085.61898.9e. PubMed DOI

Tölle T, Xu X, Sadosky AB. Painful diabetic neuropathy: a cross-sectional survey of health state impairment and treatment patterns. J Diabetes Complicat. 2006;20:26–33. doi: 10.1016/j.jdiacomp.2005.09.007. PubMed DOI

Schmader KE. Epidemiology and impact on quality of life of postherpetic neuralgia and painful diabetic neuropathy. Clin J Pain. 2002;18:350–4. doi: 10.1097/00002508-200211000-00002. PubMed DOI

Davies M, Brophy S, Williams R, Taylor A. The prevalence, severity, and impact of painful diabetic peripheral neuropathy in type 2 diabetes. Diabetes Care. 2006;29:1518–22. doi: 10.2337/dc05-2228. PubMed DOI

Huizinga MM, Peltier A. Painful diabetic neuropathy: a management-centered review. Clin Diabetes. 2007;25:6–15. doi: 10.2337/diaclin.25.1.6. DOI

Jensen TS, Backonja MM, Hernández Jiménez S, et al. New perspectives on the management of diabetic peripheral neuropathic pain. Diab Vasc Dis Res. 2006;3:108–19. doi: 10.3132/dvdr.2006.013. PubMed DOI

Rudroju N, Bansal D, Talakokkula ST, et al. Comparative efficacy and safety of six antidepressants and anticonvulsants in painful diabetic neuropathy: a network meta-analysis. Pain Physician. 2013;16:E705–14. PubMed

Vinik AI, Tuchman M, Safirstein B, et al. Lamotrigine for treatment of pain associated with diabetic neuropathy: results of two randomized, double-blind, placebo-controlled studies. Pain. 2007;128:169–79. doi: 10.1016/j.pain.2006.09.040. PubMed DOI

Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14:162–73. doi: 10.1016/S1474-4422(14)70251-0. PubMed DOI PMC

Anand P, Bley K. Topical capsaicin for pain management: therapeutic potential and mechanisms of action of the new high-concentration capsaicin 8% patch. Br J Anaesth. 2011;107:490–502. doi: 10.1093/bja/aer260. PubMed DOI PMC

Backonja M, Wallace MS, Blonsky ER, et al. NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia: a randomised, double-blind study. Lancet Neurol. 2008;7:1106–12. doi: 10.1016/S1474-4422(08)70228-X. PubMed DOI

Brown S, Simpson DM, Moyle G, et al. NGX-4010, a capsaicin 8% patch, for the treatment of painful HIV-associated distal sensory polyneuropathy: integrated analysis of two phase III, randomized, controlled trials. AIDS Res Ther. 2013;10:5. doi: 10.1186/1742-6405-10-5. PubMed DOI PMC

Haanpää M, Cruccu G, Nurmikko T, et al. Capsaicin 8% patch versus oral pregabalin in patients with peripheral neuropathic pain. Eur J Pain. 2016;20:316–28. doi: 10.1002/ejp.731. PubMed DOI PMC

Irving GA, Backonja MM, Dunteman E, et al. A multicenter, randomized, double-blind, controlled study of NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia. Pain Med. 2011;12:99–101. doi: 10.1111/j.1526-4637.2010.01004.x. PubMed DOI

Simpson DM, Brown S, Tobias J, for the NGX-4010 C107 Study Group Controlled trial of high-concentration capsaicin patch for treatment of painful HIV neuropathy. Neurology. 2008;70:2305–13. doi: 10.1212/01.wnl.0000314647.35825.9c. PubMed DOI

Simpson DM, Robinson-Papp J, Van J, Stoker M, et al. Capsaicin 8% Patch in Painful Diabetic Peripheral Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Study. J Pain. 2016. [Epub ahead of print]. PubMed

Vinik EJ, Hayes RP, Oglesby A, et al. The development and validation of the Norfolk QOL-DN, a new measure of patients’ perception of the effects of diabetes and diabetic neuropathy. Diabetes Technol Ther. 2005;7:497–508. doi: 10.1089/dia.2005.7.497. PubMed DOI

Astellas Pharma Ltd. QUTENZA™ 179 mg cutaneous patch SPC (2015). Available at https://www.medicines.org.uk/emc/medicine/23156. Accessed 4 Apr 2016.

Boyd A, Casselini C, Vinik E, Vinik A. Quality of life and objective measures of diabetic neuropathy in a prospective placebo-controlled trial of ruboxistaurin and topiramate. J Diabetes Sci Technol. 2011;5:714–22. doi: 10.1177/193229681100500326. PubMed DOI PMC

Singleton J, Bixby B, Russel JW, et al. The Utah early neuropathy scale: a sensitive clinical scale for early sensory predominant neuropathy. J Peripher Nerv Syst. 2008;13:218–27. doi: 10.1111/j.1529-8027.2008.00180.x. PubMed DOI

Casellini CM, Barlow PM, Rice AL, Casey M, Simmons K, Pittenger G, et al. A 6-month, randomized, double-masked, placebo-controlled study evaluating the effects of the protein kinase C-beta inhibitor ruboxistaurin on skin microvascular blood flow and other measures of diabetic peripheral neuropathy. Diabetes Care. 2007;30:896–902. doi: 10.2337/dc06-1699. PubMed DOI

Maier C, Baron R, Tölle TR, et al. Quantitative sensory testing in the German research network on neuropathic pain (DFNS): somatosensory abnormalities in 1236 patients with different neuropathic pain syndromes. Pain. 2010;150:439–50. doi: 10.1016/j.pain.2010.05.002. PubMed DOI

Backonja MM, Attal N, Baron R, et al. Value of quantitative sensory testing in neurological and pain disorders: NeuPSIG consensus. Pain. 2013;154:1807–19. doi: 10.1016/j.pain.2013.05.047. PubMed DOI

Zobrazit více v PubMed

ClinicalTrials.gov
NCT01478607