Elsevier

The Lancet Neurology

Volume 7, Issue 12, December 2008, Pages 1106-1112
The Lancet Neurology

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NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia: a randomised, double-blind study

https://doi.org/10.1016/S1474-4422(08)70228-XGet rights and content

Summary

Background

The limitations of current treatments for postherpetic neuralgia (PHN) have led to the investigation of localised, non-systemic alternatives. NGX-4010, a high-concentration (8%) capsaicin dermal patch, was developed to treat patients with neuropathic pain. We report the results of a randomised, double blind, 12-week study of the efficacy and safety of one application of NGX-4010 in patients with PHN.

Methods

In this multicentre, double-blind, parallel-group trial, 402 patients were randomly assigned to one 60-min application of NGX-4010 (640 μg/cm2 [8% capsaicin]) or a low-concentration capsaicin control patch (3·2 μg/cm2 [0·04% capsaicin]). Patients were aged 18–90 years, had had postherpetic neuralgia for at least 6 months, and had an average baseline numeric pain rating scale (NPRS) score of 3 to 9. The primary efficacy endpoint was percentage change in NPRS score from baseline to weeks two to eight. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00115310.

Findings

Patients who were randomly assigned to NGX-4010 (n=206) had a significantly greater reduction in pain during weeks two to eight than did patients who had the control patch (n=196). The mean changes in NPRS score were −29·6% vs −19·9% (difference −9·7%, 95% CI −15·47 to −3·95; p=0·001). 87 (42%) patients who received NGX-4010 and 63 (32%) controls had a 30% or greater reduction in mean NPRS score (odds ratio [OR] 1·56, 95% CI 1·03 to 2·37; p=0·03). The patients who had NGX-4010 had significant improvements in pain during weeks two to 12 (mean change in NPRS score −29·9% vs −20·4%, difference −9·5, −15·39 to −3·61; p=0·002). Transient blood pressure changes associated with changes in pain level were recorded on the day of treatment, and short-lasting erythema and pain at the site of application were common, self-limited, and generally mild to moderate in the NGX-4010 group and less frequent and severe in the controls.

Interpretation

One 60-min application of NGX-4010 provided rapid and sustained pain relief in patients with postherpetic neuralgia. No adverse events were associated with treatment except for local reactions at the site of application and those related to treatment-associated pain.

Funding

NeurogesX.

Introduction

Postherpetic neuralgia (PHN) is a chronic pain disorder that results from reactivation of varicella zoster.1, 2, 3, 4, 5 Treatments for PHN are often restricted owing to adverse effects and poor tolerability (tricyclic antidepressants, opioids, and anticonvulsants), their slow onset of action (tricyclic antidepressants and anticonvulsants), and the need to titrate the drugs and take several doses of the medication each day.1, 2, 5, 6, 7, 8, 9, 10 These limitations of the currently available drugs have stimulated interest in localised, non-systemic approaches to manage neuropathic pain.11, 12, 13

Capsaicin, an agonist of the transient receptor potential vanilloid 1 receptor (TRPV1), can give relief from chronic pain syndromes, including PHN and diabetic neuropathy, when applied topically.14, 15, 16, 17 Capsaicin activates TRPV1 ligand-gated cation channels on nociceptive nerve fibres, causing depolarisation, the initiation of an action potential, and the transmission of pain signals to the spinal cord. After exposure to capsaicin, TRPV1-containing sensory axons are desensitised, which inhibits the initiation of pain transmission.14

Standard, low-concentration, capsaicin-containing creams (0·025% and 0·075%) require many applications per day, cause a burning sensation at the site of application, and achieve only modest pain relief.14, 16, 18 NGX-4010 is a high-concentration (8%) capsaicin dermal patch that delivers a therapeutic dose of capsaicin in one short application. Relief from neuropathic pain after treatment with NGX-4010 has been shown in phase II and phase III studies of patients infected with HIV who have associated painful distal sensory polyneuropathy19, 20 and in a phase II study of patients with PHN.21

This randomised, double-blind, phase III study was done to extend the phase II observations by evaluating the efficacy, tolerability, and safety of one 60-min application of NGX-4010 for 12 weeks after treatment in patients with PHN.

Section snippets

Patients

Patients aged 18–90 years old who were diagnosed with PHN and had an average numeric pain rating scale22 (NPRS) score of 3–9 (inclusive) were eligible if at least 6 months had passed since crusting of their shingles vesicles. Patients who took long-term pain medications were included if they had been on stable doses of these medications for at least 21 days before treatment and stayed on a stable dose during the study period. Long-term pain medications could include oral or transdermal opioids

Results

Between June 9, 2005, and Aug 24, 2006, 402 patients at 55 research centres in the USA were enrolled in the study (figure 1). One patient was randomly assigned to NGX-4010 but instead received the control; this patient was included in the NGX-4010 group for efficacy analyses and the control group for safety analyses (table 1).

9% of patients in each treatment group (19 in NGX-4010 group and 18 in control group) withdrew from the study early; the most common reason for early withdrawal from both

Discussion

We show that one 60-min application of NGX-4010 can reduce PHN-associated pain for up to 12 weeks and that NGX-4010 was more effective at reducing pain throughout the 12-week study period than the control patch. These results extend preliminary observations of the efficacy of NGX-4010 in patients with PHN, and support the results of a 12-week, controlled, phase III trial, in which one application of NGX-4010 conferred 3 months of pain relief in patients with HIV-related distal sensory

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