A Randomized, Double-Blind, Controlled Study of NGX-4010, a Capsaicin 8% Dermal Patch, for the Treatment of Painful HIV-Associated Distal Sensory Polyneuropathy

Clifford, David B. MD*; Simpson, David M. MD; Brown, Stephen MD; Moyle, Graeme MD§; Brew, Bruce J. MD; Conway, Brian MD; Tobias, Jeffrey K. MD#; Vanhove, Geertrui F. MD, PhD#; For the NGX-4010 C119 Study Group

JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0b013e31823e31f7
Clinical Science
Abstract

Introduction: Effective treatment of HIV-associated distal sensory polyneuropathy remains a significant unmet therapeutic need.

Methods: In this randomized, double-blind, controlled study, patients with pain due to HIV-associated distal sensory polyneuropathy received a single 30-minute or 60-minute application of NGX-4010—a capsaicin 8% patch (n = 332)—or a low-dose capsaicin (0.04%) control patch (n = 162). The primary endpoint was the mean percent change from baseline in Numeric Pain Rating Scale score to weeks 2–12. Secondary endpoints included patient global impression of change at week 12.

Results: Pain reduction was not significantly different between the total NGX-4010 group (−29.5%) and the total control group (−24.5%; P = 0.097). Greater pain reduction in the 60-minute (−30.0%) versus the 30-minute control group (−19.1%) prevented intended pooling of the control groups to test individual NGX-4010 treatment groups. No significant pain reduction was observed for the 30-minute NGX-4010 group compared with 30-minute control (−26.2% vs.−19.1%, respectively, P = 0.103). Pain reductions in the 60-minute NGX-4010 and control groups were comparable (−32.8% vs. −30.0%, respectively; P = 0.488). Posthoc nonparametric testing demonstrated significant differences favoring the total (P = 0.044) and 30-minute NGX-4010 groups (P = 0.035). Significantly, more patients in the total and 30-minute NGX-4010 group felt improved on the patient global impression of change versus control (67% vs. 55%, P = 0.011 and 65% vs. 45%, P = 0.006, respectively). Mild to moderate transient application site pain and erythema were the most common adverse events.

Conclusions: Although the primary endpoint analyses were not significant, trends toward pain improvement were observed after a single 30-minute NGX-4010 treatment.

Author Information

*Department of Neurology, Washington University School of Medicine, St. Louis, MO

Department of Neurology, Mount Sinai School of Medicine, New York, NY

AIDS Research Alliance, Los Angeles, CA

§Chelsea and Westminster Hospital, London, UK

Departments of Neurology and HIV Medicine St Vincent's Hospital and St Vincent's Centre for Applied Medical Research Sydney, NSW, Australia

Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC, Canada

#NeurogesX, Inc, San Mateo, CA

Correspondence to: David B. Clifford, MD, Washington University School of Medicine, Box 8111, 660 South Euclid, St. Louis, MO 63110 (e-mail: cliffordd@neuro.wustl.edu).

This study was funded by NeurogesX, Inc. Editorial assistance was provided by Adelphi Communications Ltd, supported by Astellas Pharma Europe Ltd.

Part of these data were previously presented at the 17th Conference on Retroviruses and Opportunistic Infections, February 16–19, 2010, San Francisco, CA.

Dr. Vanhove is a former employee of NeurogesX, Inc. and currently holds stock in the company. Dr. J.K.T. is a former employee with stock in NeurogesX, Inc., Dr. G.F.V. holds stock in NuerogesX, Inc., and Dr. D.B.C., Dr. S.B. and Dr. B.C. have received grants from NeurogesX, Inc. in the past.

Trial registration: ClinicalTrials.gov NCT00321672.

The members of the ANRS 12222 Morbidity/Mortality Study Group are listed in Appendix I.

Received July 1, 2011

Accepted October 20, 2011

© 2012 Lippincott Williams & Wilkins, Inc.