(787): A multicenter, double-blind, randomized, placebo controlled study of the efficacy/safety of two doses of amitriptyline/ketamine topical cream in treating post-herpetic neuralgia (PHN)

Abstract

Treating chronic pain is a challenge (severe side-effects of systemic drugs). When efficacious, topically delivered drugs are excellent alternatives. This study was conducted to evaluate the efficacy and safety of amitriptyline 4%/ketamine 2% [NP-H] and amitriptyline 2% /ketamine1% [NP-L] topical creams versus placebo in 251 PHN patients. Patients applied the NP-H twice daily for one week. Of this group, 129 subjects met the entry criteria for randomization (> one point decrease in average daily pain (ADPS) for 3 of the seven days). In this group, the ADPS (NRS 0-10) changed from 6.5 + 1.7 at baseline to 3.8 + 1.8 at the end of one week (p< 0.0001), a decrease of 42%. Of these, 118 were entered into the second phase in which the patients were randomized to placebo, NP-H, or NP-L cream applied b.i.d. for 14 days. Although the placebo subjects did not return to baseline, (4.5 + 2.0 to 4.4 + 2.2), the NP-H group, had an additional decrease in ADPS from day 8 to day 21 from 4.4 + 2.1 to 3.3 + 2.1. The difference between NP-H and placebo at day 21 was statistically significant (p=0.03). The primary analysis, change in daily average pain intensity from baseline (day 1) to day 21, was also statistically significant between NP-H and placebo (p=0.026). A responder analysis (>30% decrease in ADPS between day 8 and day 21) demonstrated that NP-H was superior to placebo (46% versus 19%, p<0.025) Patient global satisfaction and was significantly better for NP-H versus placebo (p=0.04). NP-H was superior to placebo for change in sleep quality from baseline to day 21 (p=0.028). NP-H was numerically superior to NP-L cream and appears to be the optimal concentration for PHN treatment. Less than 5% of subjects who applied NP-H had detectable levels of amitriptyline or ketamine. Treating chronic pain is a challenge (severe side-effects of systemic drugs). When efficacious, topically delivered drugs are excellent alternatives. This study was conducted to evaluate the efficacy and safety of amitriptyline 4%/ketamine 2% [NP-H] and amitriptyline 2% /ketamine1% [NP-L] topical creams versus placebo in 251 PHN patients. Patients applied the NP-H twice daily for one week. Of this group, 129 subjects met the entry criteria for randomization (> one point decrease in average daily pain (ADPS) for 3 of the seven days). In this group, the ADPS (NRS 0-10) changed from 6.5 + 1.7 at baseline to 3.8 + 1.8 at the end of one week (p< 0.0001), a decrease of 42%. Of these, 118 were entered into the second phase in which the patients were randomized to placebo, NP-H, or NP-L cream applied b.i.d. for 14 days. Although the placebo subjects did not return to baseline, (4.5 + 2.0 to 4.4 + 2.2), the NP-H group, had an additional decrease in ADPS from day 8 to day 21 from 4.4 + 2.1 to 3.3 + 2.1. The difference between NP-H and placebo at day 21 was statistically significant (p=0.03). The primary analysis, change in daily average pain intensity from baseline (day 1) to day 21, was also statistically significant between NP-H and placebo (p=0.026). A responder analysis (>30% decrease in ADPS between day 8 and day 21) demonstrated that NP-H was superior to placebo (46% versus 19%, p<0.025) Patient global satisfaction and was significantly better for NP-H versus placebo (p=0.04). NP-H was superior to placebo for change in sleep quality from baseline to day 21 (p=0.028). NP-H was numerically superior to NP-L cream and appears to be the optimal concentration for PHN treatment. Less than 5% of subjects who applied NP-H had detectable levels of amitriptyline or ketamine.