To evaluate the efficacy, safety, and tolerability of repeated NGX-4010 treatments in the open-label extension phase of a 52-week study in patients with neuropathic pain due to HIV-associated distal sensory polyneuropathy (HIV-DSP).
Patients completing the 12-week, randomized, double-blind phase of the study could enter a 40-week, open-label phase, and receive up to 3, 60-minute NGX-4010 treatments. Patients recorded their “average pain for the past 24 hours” daily using the Numeric Pain Rating Scale (NPRS). Efficacy assessment included the percentage NPRS score reduction from baseline to weeks 2 to 12 after the final treatment, and Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) questionnaires at study termination.
Of 307 patients randomized, 272 entered the open-label phase; 81, 90, 55, and 46 received 0, 1, 2, and 3 retreatments, respectively. The mean percentage decrease in NPRS score from baseline to weeks 2 to 12 after the final treatment was similar in patients receiving single or multiple NGX-4010 treatments (−25.8%, −27.1%, −24.6%, and −22.7% for 1, 2, 3, and 4 NGX-4010 treatments, respectively). PGIC and CGIC results demonstrated a benefit of NGX-4010 treatment through to the end of the study regardless of the number of treatments received. Transient local application site reactions were the most frequently reported adverse events, and were mainly mild to moderate, nonserious, and did not increase with repeated treatment.
Repeated NGX-4010 treatments were generally well tolerated and resulted in consistent reductions in HIV-DSP-associated pain and improvement in patient-reported outcomes.
*Clinical Neurophysiology Laboratories and Neuro-AIDS Program, Department of Neurology, The Mount Sinai Medical Center, New York, NY
†AIDS Research Alliance, Los Angeles, CA
‡NeurogesX Inc., San Mateo, CA
NGX-4010 C107 Study Group: Martin Mollen, Arizona Clinical Research; James Sampson, The Research and Education Group; Suzanne Gazda, Integra Clinical Research, LLC; David Brand, North Dallas Center for AIDS & Clinical Research; Barry Cutler, Neurology Clinical Research Inc.; David Clifford, Washington University School of Medicine; Amy Colson, Community Research Initiative of New England; Ronald Ellis, University of California, San Diego; George Drusano, Albany Medical Center; Victor Valcour, HACRP-University of Hawaii; Claire Borkert, East Bay AIDS Center; Grace McComsey, Case Western Reserve; Russell Bartt, Cook County Hospital; Edwin De Jesus, Orlando Immunology Center; Ann Morris, Community Research Initiative of New England; Robert Myers, Body Positive; Corklin Steinhart, Steinhart Medical Associates; Yuen So, Stanford University Medical Center; Joe Berger, University of Kentucky; Colin Hall, University of North Carolina at Chapel Hill; Justin McArthur, Johns Hopkins University; Michael Rubin, New York Presbyterian Hospital; Alex Tselis, Wayne State University; Jose Castro, University of Miami School of Medicine; Dean Rider, Rider Research Group; Cynthia Brinson, Central Texas Clinical Research; Harold Martin, Park Nicollet Clinic; Gerald Pierone, Treasure Coast Infectious Disease Consultants; Leslie Diaz, Infectious Disease of the Palm Beaches Associates.
This study is registered at www.clinicaltrials.gov as number NCT00064623.
D.M.S. has received consultancy fees and/or honorarium or speaker fees from NeurogesX, Astellas Pharma Europe Ltd., Eli Lilly, and Pfizer. D.M.S.’s institute has received grants from NeurogesX, AstraZeneca, and Pfizer. S.B.’s institute, AIDS Research Alliance, received grants to conduct the research. J.K.T. and G.F.V. are former employees of NeurogesX and still own stock in NeurogesX. J.K.T. and G.F.V. are no longer employees of NeurogesX, they are now both employees of Jazz Pharmaceuticals, Palo Alto, CA. Study supported by NeurogesX Inc. Editorial assistance was provided by Adelphi Communications, supported by Astellas Pharma Europe Ltd, Chertsey, Surrey, UK. Editorial assistance included assistance with drafting the manuscript, copy editing, liaising with authors to gain comments and approvals, redrawing of figures and support with submission.
D.M.S and S.B conducted the study, analyzed and interpreted the data, and prepared and edited the manuscript. J.K.T and G.F.V designed the study, analyzed and interpreted the data, and prepared and edited the manuscript. All authors read and approved the final manuscript.
Reprints: David M. Simpson, MD, FAAN, Clinical Neurophysiology Laboratories and Neuro-AIDS Program, Department of Neurology, The Mount Sinai Medical Center, Box 1052, New York, NY 10029 (e-mail: email@example.com).
Received October 5, 2011
Accepted January 12, 2013