NGX-4010, a capsaicin 8% patch, for the treatment of painful HIV-associated distal sensory polyneuropathy: integrated analysis of two phase III, randomized, controlled trials

Abstract

Background: HIV-associated distal sensory polyneuropathy (HIV-DSP) is the most frequently reported neurologic complication associated with HIV infection. NGX-4010 is a capsaicin 8% dermal patch with demonstrated efficacy in the treatment of HIV-DSP. Data from two phase III, double-blind studies were integrated to further analyze the efficacy and safety of NGX-4010 and explore the effect of demographic and baseline factors on NGX-4010 treatment in HIV-DSP.

Methods: Data from two similarly designed studies in which patients with HIV-DSP received NGX-4010 or a low-concentration control patch (capsaicin 0.04% w/w) for 30 or 60 minutes were integrated. Efficacy assessments included the mean percent change from baseline in Numeric Pain Rating Scale (NPRS) scores to Weeks 2-12. Safety and tolerability assessments included adverse events (AEs) and pain during and after treatment.

Results: Patients (n = 239) treated with NGX-4010 for 30 minutes demonstrated significantly (p = 0.0026) greater pain relief compared with controls (n = 100); the mean percent change in NPRS scores from baseline to Weeks 2-12 was -27.0% versus -15.7%, respectively. Patients who received a 60-minute application of NGX-4010 (n = 243) showed comparable pain reductions (-27.5%) to patients treated for 30 minutes, but this was not statistically superior to controls (n = 115). NGX-4010 was effective regardless of gender, baseline pain score, duration of HIV-DSP, or use of concomitant neuropathic pain medication, although NGX-4010 efficacy was greater in patients not receiving concomitant neuropathic pain medications. NGX-4010 was well tolerated; the most common AEs were application-site pain and erythema, and most AEs were mild to moderate. The transient increase in pain associated with NGX-4010 treatment decreased the day after treatment and returned to baseline by Day 2.

Conclusions: A single 30-minute application of NGX-4010 provides significant pain relief for at least 12 weeks in patients with HIV-DSP and is well tolerated.

Trial registration: C107 = NCT00064623; C119 = NCT00321672.

Figure 1

Disposition of all patients from both phase III HIV-DSP studies used in the integrated analysis. *One patient randomly assigned to receive the 30-minute control treatment received the 60-minute control treatment.

Figure 2

Pain reduction following a single 30-minute application of NGX-4010. (A) Weekly analysis of least squares mean change (± standard error) in Numeric Pain Rating Scale (NPRS) score from baseline for the integrated 30-minute treatment group. (B) Daily analysis of mean change in NPRS score from baseline for the integrated 30-minute treatment group.

Figure 3

Mean percent change in NPRS score. Change in NPRS score from baseline to Weeks 2–12 for the 30-minute treatment groups. Analysis by subgroup: (A) gender; (B) baseline pain score; (C) concomitant neuropathic pain medication use; and (D) duration of HIV-DSP. *A patient was defined as receiving concomitant neuropathic pain medication if he or she was taking an anticonvulsant, non-SSRI antidepressant, or opioid on Day −1 and for a total duration of at least 7 consecutive days.

Figure 4

Percentage of patients with ≥30% reduction in NPRS score from baseline to weeks 2–12. Patients in the 30-minute treatment groups; analysis by subgroup: (A) gender; (B) baseline pain score; (C) concomitant neuropathic pain medication use; and (D) duration of HIV-DSP. *Concomitant medication was defined as in Figure 3.