Study of NGX-4010 for the Treatment of Painful HIV-Associated Neuropathy
Condition: Pain; HIV Infections; Peripheral Nervous System Diseases
MeSH terms: Nervous System Diseases; Peripheral Nervous System Diseases
Intervention: NGX-4010, 8% capsaicin patch; 0.04% capsaicin patch; NGX-4010, 8% capsaicin patch; 0.04% capsaicin patch
Intervention description: Up to 4 NGX-4010 patches of 280 cm^2 each were applied to the feet (2 per foot) for 60 minutes.; Up to 4 control patches of 280 cm^2 each were applied to the feet (2 per foot) for 60 minutes.; Up to 4 NGX-4010 patches of 280 cm^2 each were applied to the feet (2 per foot) for 30 minutes.; Up to 4 control patches of 280 cm^2 each were applied to the feet (2 per foot) for 30 minutes.
Intervention MeSH terms: Capsaicin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 494.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Analgesics; Capsaicin; Neuropathic pain; Neuropathy; Distal sensory polyneuropathy; Peripheral neuropathy; Dermal assessment; Pain measurement

Summary:

      The purpose of the study was to assess the efficacy and safety of NGX-4010 applied for 30 or
      60 minutes for the treatment of painful HIV-associated neuropathy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Documented evidence of HIV-1 infection

          -  Documented diagnosis of painful HIV-associated distal symmetric polyneuropathy
             resulting from HIV disease and/or antiretroviral drug exposure To be confirmed based
             on symptoms of pain, burning or dysesthetic discomfort in both feet for at least 2
             months prior to Screening Visit, AND absent or diminished ankle reflexes OR at least
             one of following: distal diminution of vibration sensation or pain or temperature
             sensation 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 to
             Day 0 and willing to maintain medications at same stable dose(s) and schedule
             throughout study

          -  Female subjects with child-bearing potential: negative serum pregnancy test performed
             at Screening Visit

          -  Willing to use effective methods of birth control and/or refrain from conception
             process 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 not
             exceeding total daily dose of morphine 80 mg/day or equivalent; parenteral opioids not
             allowed

          -  Unavailability of effective rescue medication strategy for subject, such as
             unwillingness to use opioid analgesics during study treatment or high tolerance to
             opioids precluding ability to relieve treatment-associated discomfort as judged by
             investigator

          -  Active substance abuse or history of chronic substance abuse within past year or prior
             chronic substance abuse (including alcoholism) judged likely to recur during study
             period 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, local
             anesthetics including Lidoderm® (lidocaine patch 5%), steroids or capsaicin products
             on 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 or
             open-label NGX-4010

          -  Current use of any investigational agent or Class 1 anti-arrhythmic drugs (such as
             tocainide and mexiletine)

          -  Evidence of another contributing cause for peripheral neuropathy, e.g., current
             uncontrolled diabetes mellitus (HbA1c≥9%) or history of diabetes mellitus preceding
             onset of HIV-associated neuropathy (HIV-AN); hereditary neuropathy; vitamin B12
             deficiency (B12 level ≤200pg/mL at screening); or treatment within 90 days prior to
             Screening 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-AN
             related pain

          -  Any implanted medical device for treatment of neuropathic pain

          -  Hypersensitivity to capsaicin (i.e., chili peppers or over-the-counter (OTC) capsaicin
             products), local anesthetics, opioid-based oral analgesics or adhesives

          -  Significant medical conditions (including active malignancy defined as treatment
             required in last 5 years) that in opinion of investigator would interfere with ability
             to complete study or evaluation of AEs

          -  Recent significant medical-surgical intervention that in judgment of Investigator
             would interfere with ability to complete study or evaluation of AEs; examples include
             to 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's
             ability to complete daily pain diaries requiring recall of average HIV-associated
             neuropathy pain level in past 24 hours