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

• Absolute Change in the Mean "Average Pain for the Past 24 Hours" Numeric Pain Rating Scale (NPRS) Score From Baseline During Weeks 2 to 12. [ Time Frame: Weeks 2-12. ] [ Designated as safety issue: No ]
• Proportion of Subjects Reaching 30% Decrease in Their Mean "Average Pain for the Past 24 Hours" Numeric Pain Rating Scale (NPRS) Score From Baseline During Weeks 2 to 12 [ Time Frame: Weeks 2-12 ] [ Designated as safety issue: No ]

• Percent change from baseline in average pain NPRS score (i.e., average of scores during Weeks 2 to 8, compared to baseline)
• Proportion of subjects reaching 30% and 50% decrease, respectively, from baseline in "average pain" NPRS score

Study C119 was a multicenter, randomized, double-blind, controlled evaluation of the efficacy and safety of NGX-4010 for the treatment of painful HIV-associated neuropathy. Eligible subjects had painful HIV-associated neuropathy resulting from HIV disease and/or antiretroviral drug exposure in both feet, with average numeric pain rating scale (NPRS) scores during screening of 3 to 9 (inclusive). Up to four patches covering an area of up to 1120 square centimeters could be used during a single treatment administration in this study. Subjects were randomly assigned to receive active NGX-4010 patches (8% capsaicin) or low-concentration control patches (0.04% capsaicin) identical in appearance, at doses (patch application duration) of either 30 or 60 minutes, according to a 2:1:2:1 allocation scheme.

Subjects could be on stable chronic oral pain medication regimens, but could not be using any topical pain medications on the affected areas. NPRS scores for the average pain in the past 24 hours were recorded daily in the evening, beginning on the day of the Screening Visit (usually on Day -14). Subjects continued to record NPRS scores in a take-home diary from the evening on the day of treatment through the evening before the Termination Visit at Week 12. Subjects returned for interim follow-up visits at Weeks 4 and 8 following study treatment.

• Pain
• HIV Infections
• Peripheral Nervous System Diseases

• Drug: NGX-4010, 8% capsaicin patch
  Up to 4 NGX-4010 patches of 280 cm^2 each were applied to the feet (2 per foot) for 60 minutes.
  Other Name: the brandname of NGX-4010, 8% capsaicin patch is Qutenza.
• Drug: 0.04% capsaicin patch
  Up to 4 control patches of 280 cm^2 each were applied to the feet (2 per foot) for 60 minutes.
  Other Name: NGX-4010
• Drug: NGX-4010, 8% capsaicin patch
  Up to 4 NGX-4010 patches of 280 cm^2 each were applied to the feet (2 per foot) for 30 minutes.
  Other Name: The brandname of NGX-4010, 8% capsaicin patch is Qutenza.
• Drug: 0.04% capsaicin patch
  Up to 4 control patches of 280 cm^2 each were applied to the feet (2 per foot) for 30 minutes.
  Other Name: NGX-4010

• Experimental: NGX-4010, 60 minutes
  Intervention: Drug: NGX-4010, 8% capsaicin patch
• Experimental: NGX-4010, 30 minutes
  Intervention: Drug: NGX-4010, 8% capsaicin patch
• 0.04% conc. capsaicin patch, 60 min.
  Intervention: Drug: 0.04% capsaicin patch
• 0.04% conc. capsaicin patch, 30 min.
  Intervention: Drug: 0.04% capsaicin patch

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