Abstract
While capsaicin topical formulations are established treatments, conventional creams using this substance have limited application due to handling-related adverse events. This study aimed to demonstrate that the efficacy of a novel 0.75 mg/g capsaicin roll-on solution is non-inferior to the approved 0.75 mg/g cream in patients with painful diabetic neuropathy (PDN). In total, 160 patients were randomized to receive either the roll-on or the cream, applied four times daily for 8 weeks, followed by a 4-week washout period and crossover to the alternate treatment. The primary endpoint was pain intensity (numerical rating scale), with secondary endpoints including quality of life (EQ-5D) and safety. Both groups showed significant reductions in pain, with no statistically significant differences in absolute (p = 0.115) or relative (p = 0.157) pain reduction. Non-inferiority was confirmed with a 95% CI for the difference in mean pain reduction [-0.86-0.07], remaining within the pre-specified margin (1.0 unit). Quality of life improved in both groups, with no significant differences (p = 0.266). The incidence of adverse events was low and predominantly mild, with no significant differences between groups (p = 0.424) and a favorable trend for the roll-on formulation. The roll-on capsaicin formulation demonstrated non-inferiority in efficacy and safety compared with the conventional cream formulation.