Effect of NGX-4010 on ENFD and Sensory Function

This is a randomized, controlled, open-label, single center, phase 1 study in normal healthy volunteers. Each subject will have a 60 minute exposure to two 5.0 × 5.5 cm NGX-4010 patches. In addition, two 5.0 × 5.5 cm comparable untreated control skin areas will be identified and evaluated. At baseline and prior to skin punch biopsy at Weeks 1 (± 1 day), 12 (± 3 days) and 24 (± 7 days), QST of patch-treated and untreated control skin areas will be performed and evaluated. QST for cooling detection threshold and heat-pain threshold, and assessment of mechanical (sharp pain) sensation and tactile threshold will be performed at each of the two patch-treated and two untreated control skin areas. Serial skin punch biopsies of patch-treated and untreated control skin areas will be obtained and evaluated at Weeks 1 (± 1 day), 12 (± 3 days), and 24 (± 7 days). Skin at the patch-treated and untreated control skin areas will be anesthetized with subcutaneous 1% lidocaine, and then three millimeter (mm) skin biopsies will be obtained with a sterile punch tool from each of the designated areas. Biopsy specimens will be fixed overnight, then cryoprotected in a phosphate buffered solution until processed. Thick sections will be cut and immunostained for localization and quantification of nerve fibers in the epidermis and visualization of the subepidermal plexus using antibodies to PGP 9.5. Antibodies to type IV collagen will be used to identify the basement membrane and superficial blood vessels in the biopsy microsections. Vital signs and adverse events (AEs) will be collected at each visit. Clinical laboratory tests will be performed at the Screening Visit and at the Termination Visit (Week 24).