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. 2025 Sep 24;15(10):1507.
doi: 10.3390/life15101507.

Non-Inferiority Study of Two Capsaicin Formulations for Painful Diabetic Neuropathy

Tamara Rodríguez Araya  1 , Francisco Abad-Santos  2   3 , José Miguel Sempere Ortells  4 , Juan Nieto Navarro  5 , Pablo González-López  6 , Javier Abarca-Olivas  6 , Elena Baño Ruiz  6 , Carlos Iglesias-García  7 , José Fernando Villalba García  4
Affiliations

Non-Inferiority Study of Two Capsaicin Formulations for Painful Diabetic Neuropathy

Tamara Rodríguez Araya et al. Life (Basel). .

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.

Keywords: capsaicin; crossover study; non-inferiority clinical trial; painful diabetic peripheral neuropathy; safety.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Study flow and treatment regimen scheme.
Figure 2
Figure 2
Population groups.
Figure 3
Figure 3
Evolution of the numerical pain intensity scale score 8 weeks after the first ITT treatment sequence. * p < 0.05.
Figure 4
Figure 4
Evolution of the numerical pain intensity scale score in both IT treatment sequences.
Figure 5
Figure 5
Evolution of the numerical pain intensity scale score 8 weeks after the first PP treatment sequence. * p < 0.05.
See this image and copyright information in PMC

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