Effect of capsaicin (8%) topical system on sensory function in patients with diabetic peripheral neuropathy: Analysis of the PACE study
Journal article
Published on April 3, 2026

Effect of capsaicin (8%) topical system on sensory function in patients with diabetic peripheral neuropathy: Analysis of the PACE study

Contributors:

Katz NP, Allen S, Carnevale A et al.

Name of journal:

Muscle & Nerve

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DOI:

10.1002/mus.70237

Topics:

DPN PRO QOL PACE Pharmacological Post-hoc analysis Peripheral neuropathic pain Randomized controlled trial Capsaicin 8% topical system
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Summary

This post-hoc analysis of the PACE study evaluated changes in peripheral sensory function over 12-months in patients with painful diabetic peripheral neuropathy (PDPN) of the feet receiving repeated 30-minute treatments with capsaicin 8% topical system (also known as high-concentration capsaicin topical system, HCCTS) plus standard of care (SOC).1 Sensory function was assessed using neurological measures (Brief Sensory Pain Examination, BSPE) and patient-reported outcomes (Norfolk Quality of Life-Diabetic Neuropathy, Norfolk QOL-DN).1

This page provides a summary of Katz NP et al. Muscle & Nerve. 2026;73:1109–1117. It is a simplified representation of the publication that was created by Averitas Pharma, and should not be considered a replacement for the full article or its abstract. This publication was developed with support from Averitas Pharma. Full author disclosures are available in the original publication. This publication contains data on sensory outcomes that extend beyond the FDA-approved labeling. Capsaicin 8% topical system is indicated for the management of neuropathic pain associated with diabetic peripheral neuropathy of the feet and postherpetic neuralgia. The safety and effectiveness of capsaicin 8% topical system for uses not described in the approved labeling have not been established. The data presented here should not be interpreted as support for uses outside the approved labeling.

Consult the Important Safety Information and Full Prescribing Information for complete details on approved indications, safety, and risks.

Background

Diabetic peripheral neuropathy (DPN) is characterized not only by neuropathic pain but also by loss of protective sensory function in the feet, which may increase the risk of injury and downstream complications.1,2

HCCTS is a transient receptor potential vanilloid 1 (TRPV1) receptor agonist and is approved in the US for the treatment of neuropathic pain associated with DPN of the feet.1

PACE was a 52–week, Phase 3, open-label, randomized controlled study in 468 patients with PDPN of the feet, designed to evaluate the safety of repeated treatment with HCCTS plus SOC versus SOC alone.1

Aim

This post-hoc analysis of the PACE study evaluated the association between repeated 30-minute HCCTS treatment plus SOC and changes in peripheral sensory function versus SOC alone in patients with PDPN, particularly those with baseline sensory deficits.1

 

In the Phase 3 PACE study, patients (N=468) were eligible to receive retreatment with HCCTS at ≥8-week intervals and could receive up to 7 treatments.1 Sensory function was assessed using the BSPE, and patient-reported outcomes related to nerve fiber function and its impact were assessed using the Norfolk QOL-DN questionnaire.1

 

A primary analysis of the PACE data showed that repeated HCCTS treatment was not associated with deterioration in nerve function, as assessed by the Norfolk QOL-DN total score, compared to SOC alone.1 However, as the primary analysis did not include formal statistical comparisons between treatment groups, additional post-hoc analyses were conducted to further evaluate the effects of repeated HCCTS treatment.3

Patient-reported nerve function outcomes were measured using the Norfolk QOL-DN questionnaire, which assesses changes in nerve function and the overall impact of nerve fiber dysfunction on QOL, daily activities, and health.<sup>1</sup> In the PACE study, the Norfolk QOL-DN total score, as well as the small and large-fiber subscales, were analyzed.<sup>1
Patient-reported nerve function outcomes were measured using the Norfolk QOL-DN questionnaire, which assesses changes in nerve function and the overall impact of nerve fiber dysfunction on QOL, daily activities, and health.1 In the PACE study, the Norfolk QOL-DN total score, as well as the small and large-fiber subscales, were analyzed.1

Key findings

Sensory function changes over time

With repeated HCCTS plus SOC treatment, more positive shifts in BSPE scores were seen across all five BSPE stimuli than negative shifts during the 12-month study period.1

Normalization of sensory function

Among patients with below-normal sensory function at baseline, as assessed by BSPE, a return to normal valuesa at Month 12 was observed in1:

Proportion of BSPE tests shifting from below-normal to normal sensation at Month 12.<sup>1</sup> Results are based on test-level analyses.<sup>1</sup> 
N number refers to number of tests, not number of patients.<sup>1</sup>
Proportion of BSPE tests shifting from below-normal to normal sensation at Month 12.1 Results are based on test-level analyses.1 
N number refers to number of tests, not number of patients.1

Statistically significant improvements versus SOC

In patients with baseline sensory deficits (n=177), statistically significant improvements in BSPE scores versus SOC alone were observed for1:

BSPE sensory test outcomes versus SOC alone in patients with baseline sensory deficits.<sup>1</sup>
BSPE sensory test outcomes versus SOC alone in patients with baseline sensory deficits.1

The observed improvements in sensory function scores were accompanied by statistically significant improvements in patient-reported outcomes related to nerve fiber function1:

Patient-reported outcomes in the Norfolk QOL-DN total score and two of its subscales (small and large fiber physical functioning) versus SOC alone in patients with baseline sensory deficits.<sup>1
Patient-reported outcomes in the Norfolk QOL-DN total score and two of its subscales (small and large fiber physical functioning) versus SOC alone in patients with baseline sensory deficits.1

Conclusions

This post-hoc analysis of the PACE study suggests that repeated 30-minute HCCTS treatment plus SOC was associated with improvements in sensory function in the feet and in patient-reported outcomes over time compared with SOC alone.1

 

As concluded by the authors, improvements in sensory function may have implications for reducing the risk of diabetic foot-related complications.1

 

Further research is needed to confirm these findings.1

Limitations

This was a post-hoc analysis of the PACE study, which was not designed or powered to detect statistically significant differences in sensory function between treatment groups.1 Subgroup analyses included relatively small numbers of patients with below-normal sensory function at baseline.1

The BSPE includes commonly used bedside neurological tests but has not been formally validated to detect clinically meaningful changes in sensory function.1 The open-label, non-placebo-controlled study design may have introduced bias in interpretation of results.1 Attrition over time and changes in mobility, medication use, and metabolic control post treatment may have influenced observed sensory outcomes.1

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Footnotes

aNormal sensory function reflects the predefined scoring criteria used in the BSPE and does not represent restoration to healthy control sensory function.
BSPE, Brief Sensory Pain Examination; DPN, diabetic peripheral neuropathy; Norfolk QOL-DN, Norfolk Quality of Life Questionnaire-Diabetic Neuropathy; PDPN, painful diabetic peripheral neuropathy; QOL, quality of life; SOC, standard of care.

QZA-04-26-0008 | June 2026