Effect of NGX-4010 on ENFD and Sensory Function
Condition: Human Volunteers
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to evaluate epidermal nerve fiber (ENF) regeneration and
      normalization of peripheral sensory nerve function over time in normal healthy volunteers
      following a 60 minute application of Capsaicin Dermal Patch (NGX 4010; capsaicin 640 mcg/cm2)
      as compared to comparable untreated skin areas (control).The objectives of this study are: 1)
      To assess the difference between patch-treated and comparable untreated skin areas (control)
      in ENFD as quantified by PGP 9.5 immunohistochemical staining of skin biopsy samples obtained
      at 1, 12 and 24 weeks following a 60 minute application; 2) To assess the difference between
      patch-treated and comparable untreated skin areas (control) for thermal detection thresholds
      as assessed by QST at 1, 12 and 24 weeks following a 60 minute application; and, 3) To assess
      the difference between patch-treated and comparable untreated skin areas (control) in
      mechanical (sharp pain) sensation and tactile threshold at 1, 12 and 24 weeks following a 60
      minute application.
    

Detailed description: 
      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).
    

Intervention name(s): NGX-4010
Intervention type(s): Drug
Intervention MeSH terms: Capsaicin
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment