Efficacy of the Nav1.7 blocker PF 05089771 in a randomised, placebo controlled, double blind clinical study in subjects with painful diabetic peripheral neuropathy
Abstract The effect of PF 05089771, a selective, peripherally restricted Nav1.7 sodium channel blocker on pain due to diabetic peripheral neuropathy was investigated in a randomised, placebo and active controlled parallel group clinical trial (NCT02215252) A 1 week placebo run in the period was followed by a 4 week treatment period and a 1 week placebo run out/taper down period. Single blind placebo was administered throughout run in and run out periods. Subjects were randomised to receive either PF 05089771 150 mg twice daily, pregabalin 150 mg twice daily, or placebo during the 4 week treatment period. One hundred thirty five subjects were randomised. The primary endpoint was the average pain score derived from subjects' Numerical Rating Scale scores over the past 7 days of week 4 of the double blind treatment period. Predefined efficacy criteria for the trial were the effect of PF 05089771 being >0.5 units better than placebo at interim analysis after completion of the first part of the study. Although a trend for a reduction in the weekly average pain score in the PF 05089771 treatment group was observed, this was not statistically significant when compared with placebo at week 4, with a mean posterior difference of 0.41 (90% credible interval: 1.00 to 0.17) The effect of PF 05089771 was smaller than that seen with pregabalin, which was statistically significant when compared with placebo at week 4, with a mean posterior difference of 0.53 (90% credible interval: 0.91 to 0.20) As predefined efficacy criteria were not met, the study did not proceed to the second part. PF 05089771 was well tolerated. Possible reasons for the modest efficacy observed with PF 05089771 are discussed.
Pain