Study of NGX-4010 for the Treatment of Painful HIV-Associated Neuropathy

Inclusion Criteria:

• Documented evidence of HIV-1 infection

• Documented diagnosis of painful HIV-associated distal symmetric polyneuropathyresulting from HIV disease and/or antiretroviral drug exposure To be confirmed basedon symptoms of pain, burning or dysesthetic discomfort in both feet for at least 2months prior to Screening Visit, AND absent or diminished ankle reflexes OR at leastone of following: distal diminution of vibration sensation or pain or temperaturesensation in legs

• Average NPRS scores during screening period of 3 to 9, inclusive

• Life expectancy of 12 months or longer per Investigator's judgment

• Intact, unbroken skin over painful areas to be treated

• If taking chronic pain medications, be on stable regimen for at least 21 days prior toDay 0 and willing to maintain medications at same stable dose(s) and schedulethroughout study

• Female subjects with child-bearing potential: negative serum pregnancy test performedat Screening Visit

• Willing to use effective methods of birth control and/or refrain from conceptionprocess during study and for 30 days following study drug exposure

• Willing and able to comply with protocol for duration of study

Exclusion Criteria:

• Concomitant opioid medication, unless orally or transdermally administered and notexceeding total daily dose of morphine 80 mg/day or equivalent; parenteral opioids notallowed

• Unavailability of effective rescue medication strategy for subject, such asunwillingness to use opioid analgesics during study treatment or high tolerance toopioids precluding ability to relieve treatment-associated discomfort as judged byinvestigator

• Active substance abuse or history of chronic substance abuse within past year or priorchronic substance abuse (including alcoholism) judged likely to recur during studyperiod by investigator

• Recent use (within 21 days preceding Day 0) of any topically applied pain medication,such as non-steroidal anti-inflammatory drugs, menthol, methyl salicylate, localanesthetics including Lidoderm® (lidocaine patch 5%), steroids or capsaicin productson painful areas

• Started or stopped treatment with one or more neurotoxic antiretroviral agents (ie,didanosine [ddI], zalcitabine [ddC], or stavudine [d4T] during 8 weeks prior to Day 0

• Participation in previous clinical trial in which subject received either blinded oropen-label NGX-4010

• Current use of any investigational agent or Class 1 anti-arrhythmic drugs (such astocainide and mexiletine)

• Evidence of another contributing cause for peripheral neuropathy, e.g., currentuncontrolled diabetes mellitus (HbA1c≥9%) or history of diabetes mellitus precedingonset of HIV-associated neuropathy (HIV-AN); hereditary neuropathy; vitamin B12deficiency (B12 level ≤200pg/mL at screening); or treatment within 90 days prior toScreening Visit with any drug that may have contributed to sensory neuropathy

• Hypertension, unless adequately controlled by medication

• Significant ongoing pain from other cause(s) that may interfere with judging HIV-ANrelated pain

• Any implanted medical device for treatment of neuropathic pain

• Hypersensitivity to capsaicin (i.e., chili peppers or over-the-counter (OTC) capsaicinproducts), local anesthetics, opioid-based oral analgesics or adhesives

• Significant medical conditions (including active malignancy defined as treatmentrequired in last 5 years) that in opinion of investigator would interfere with abilityto complete study or evaluation of AEs

• Recent significant medical-surgical intervention that in judgment of Investigatorwould interfere with ability to complete study or evaluation of AEs; examples includeto major surgery, or receipt of immunosuppressive therapy within 3 months prior to Day 0

• Evidence of cognitive impairment including dementia that may interfere with subject'sability to complete daily pain diaries requiring recall of average HIV-associatedneuropathy pain level in past 24 hours