A Randomized, Controlled, Open-Label Study of the Long-Term Effects of NGX-4010, a High-Concentration Capsaicin Patch, on Epidermal Nerve Fiber Density and Sensory Function in Healthy Volunteers

Kennedy, William R.; Vanhove, Geertrui F.; Lu, Shiao ping; Tobias, Jeffrey; Bley, Keith; Walk, David; Wendelschafer‐Crabb, Gwen; Simone, Donald A.; Selim, Mona M.

doi:10.1016/j.jpain.2009.09.019

Cited by 170 publications

(149 citation statements)

References 29 publications

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“…A single 60‐min application of a capsaicin 8% patch (hereon referred to as the capsaicin patch) rapidly delivers capsaicin into the skin, directly targeting the nociceptor leading to its defunctionalization (Malmberg et al., 2004; Kennedy et al., 2010; Anand and Bley, 2011). The efficacy and safety of the capsaicin patch in the treatment of PNP is well established (Backonja et al., 2008; Simpson et al., 2008; Irving et al., 2011; Mou et al., 2013) and it is approved for the treatment of PNP in non‐diabetic adults in the EU (QUTENZA ™ , SPC, 2014).…”

Section: Introductionmentioning

confidence: 99%

Capsaicin 8% patch versus oral pregabalin in patients with peripheral neuropathic pain

Haanpää

Cruccu

Nurmikko

et al. 2015

European Journal of Pain

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BackgroundClinical trials have not yet compared the efficacy of capsaicin 8% patch with current standard therapy in peripheral neuropathic pain (PNP).ObjectivesHead‐to‐head efficacy and safety trial comparing the capsaicin patch with pregabalin in PNP.MethodsOpen‐label, randomized, multicentre, non‐inferiority trial. Patients with PNP, aged 18–80 years, were randomly assigned to either the capsaicin 8% patch (n = 282) or an optimised dose of oral pregabalin (n = 277), and assessed for a ≥30% mean decrease in Numeric Pain Rating Scale (NPRS) score from baseline to Week 8. Secondary endpoints included optimal therapeutic effect (OTE), time‐to‐onset of pain relief and treatment satisfaction.ResultsThe capsaicin 8% patch was non‐inferior to pregabalin in achievement of a ≥30% mean decrease in NPRS score from baseline to Week 8 (55.7% vs. 54.5%, respectively; Odds ratio: 1.03 [95% CI: 0.72, 1.50]). The proportion of patients achieving OTE at Week 8 was 52.1% for the capsaicin 8% patch versus 44.8% for pregabalin (difference: 7.3%; 95% CI: −0.9%, 15.6%). The median time‐to‐onset of pain relief was significantly shorter for capsaicin 8% patch versus pregabalin (7.5 vs. 36.0 days; Hazard ratio: 1.68 [95% CI: 1.35, 2.08]; p < 0.0001). Treatment satisfaction was also significantly greater with the capsaicin 8% patch versus pregabalin. TEAEs were mild‐to‐moderate in severity, and resulted in treatment discontinuation only with pregabalin (n = 24). Systemic adverse drug reactions ranged from 0 to 1.1% with capsaicin 8% patch and 2.5 to 18.4% with pregabalin.ConclusionsThe capsaicin 8% patch provided non‐inferior pain relief to an optimized dose of pregabalin in PNP, with a faster onset of action, fewer systemic side effects and greater treatment satisfaction.

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Section: Introductionmentioning

confidence: 99%

Capsaicin 8% patch versus oral pregabalin in patients with peripheral neuropathic pain

Haanpää

Cruccu

Nurmikko

et al. 2015

European Journal of Pain

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“…[24]. After continued treatment, the TRPV1 containing nerves are "defunctionalised", a term used to describe the epidermal nerve fibre degeneration that is seen on nerve biopsy in the area of application [25]. In clinical terms, this means that initiation of treatment is associated with a burning sensation for a number of days, followed by analgesia.…”

Section: Lidocainementioning

confidence: 99%

The role of topiceuticals in cancer pain

Paisley

Serpell²

2017

Current Opinion in Supportive &Amp; Palliative Care

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Purpose of review:Pain is one of the most common and feared symptoms associated with a new diagnosis of cancer and its subsequent treatment. Unfortunately, it remains undertreated in around one third of patients. It has been recently postulated that one mechanism for this could be failure to recognise neuropathic pain. One attractive option in both the case of neuropathic pain and pain associated with intolerable side effects of prescribed opioids is the use of 'topiceuticals', as a means of targeted pain relief with potentially fewer side effects. This review summarises the evidence base for the various topiceuticals available for the treatment of localised neuropathic pain. Recent findings:The recent evidence base for established treatments such as capsaicin and lignocaine is examined. A variety of novel and previously used therapies are considered. Summary:The use of topiceuticals in localised neuropathic pain associated with malignancy remain a valuable option with many advantages over systemic treatments. In addition to anecdotal reports of efficacy, there is a growing body of evidence to consider the early use of topical lignocaine and capsaicin in this context. The authors' have proposed a guideline including the use of topiceuticals to aid in the management of neuropathic pain

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“…An alternative approach to exploit the mechanism and avoid side effects associated with systemic exposure has been to develop topical preparations (78)(79)(80). In order to avoid the acute irritation, capsaicin (8%) is administered following application of topical lidocaine and is reported to be well tolerated following repeated administration (81).…”

Section: Targeting Ion Channelsmentioning

confidence: 99%

“…In order to avoid the acute irritation, capsaicin (8%) is administered following application of topical lidocaine and is reported to be well tolerated following repeated administration (81). It is interesting to note that the mechanism of action may involve both the desensitization of the peripheral nociceptor endings and a decrease in epidermal fiber density (78).…”

Section: Targeting Ion Channelsmentioning

confidence: 99%

The discovery and development of analgesics: new mechanisms, new modalities

Burgess¹,

Williams²

2010

J. Clin. Invest.

105

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Despite intensive research into pain mechanisms and significant investment in research and development, the majority of analgesics available to prescribers and patients are based on mechanistic classes of compounds that have been known for many years. With considerable ingenuity and innovation, researchers continue to make the best of the mechanistic approaches available, with novel formulations, routes of administration, and combination products. Here we review some of the mechanisms and modalities of analgesics that have recently entered into clinical development, which, coupled with advances in the understanding of the pathophysiology of chronic pain, will hopefully bring the promise of new therapeutics that have the potential to provide improved pain relief for those many patients whose needs remain poorly met. IntroductionDrug discovery and development continue to be a challenge, with increasingly high investments in R&D and increased numbers of submissions failing to translate into the delivery of novel chemical entities onto the market. The wide availability of generic and overthe-counter analgesics based on non-steroidal antiinflammatories (NSAIDs), acetaminophen, and "weak" opiates (and their combinations) provides many individuals with an accessible source of relief for mild to moderate pain. However, many patients with chronic conditions such as osteoarthritis remain poorly treated (1, 2).Opiates continue to provide an important choice for the treatment of moderate to severe pain but are associated with a number of unwanted side effects such as constipation, nausea, vomiting, itching, and somnolence (3), and negative effects on patients' wellbeing, including sleep quality and ability to concentrate, which can be of such significance that they result in treatment discontinuation (4). Indeed, a recent Internet survey indicated that patients taking opiates for pain (and prescribing physicians) are willing to "trade-off " pain relief for a better toleration profile, with 50% of patients and physicians reporting that improved side effects represent the biggest unmet need (5).Neuropathic pain has a complex pathophysiology and is difficult to treat (6). It has been estimated that about one-third of patients are likely to achieve 50% pain relief with monotherapy (7); for example, in patients treated with the first-line therapy pregabalin, the patient global impression of change rating of much improved or very much improved was about 35% in postherpetic neuralgia, 50% in painful diabetic neuropathy, and 40% in fibromyalgia (8). A recent review identified a 66% increase in published randomized, placebo-controlled trials in a range of neuropathic pain populations over the last five years and concluded that only a limited improvement in the relief of pain had been achieved and that a large proportion of patients remained poorly treated (9).The challenge for drug discovery and development can therefore be very simply stated: we need to bring forward analgesics that will provide more effective pain relief, are safe...

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A Randomized, Controlled, Open-Label Study of the Long-Term Effects of NGX-4010, a High-Concentration Capsaicin Patch, on Epidermal Nerve Fiber Density and Sensory Function in Healthy Volunteers

Cited by 170 publications

References 29 publications

Capsaicin 8% patch versus oral pregabalin in patients with peripheral neuropathic pain

Capsaicin 8% patch versus oral pregabalin in patients with peripheral neuropathic pain

The role of topiceuticals in cancer pain

The discovery and development of analgesics: new mechanisms, new modalities

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