PACE post-hoc analysis: Sensory function outcomes in PDPN
This visual publication summary provides an enhanced, interactive overview of Katz NP et al. Muscle & Nerve. 2026;73:1109–1117. The original 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
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for complete details on approved indications, safety, and risks.
Click here to view data from the PACE post-hoc analysis
Methods overview
PACE post-hoc study design1
Sensory modalities were assessed to evaluate small- and large-fiber nerve dysfunction in PDPN.
Patients randomized
Assessments
Sensory shifts over 12 months
n=156
Sensory function among patients with below-normal sensory function at baseline
n=88 HCCTS + SOC n=89 SOC
Objectives
Primary objectives
BSPE sensory shifts at the end of the studyTo evaluate the effect of repeated 30-minute HCCTS + SOC on sensory function at 12 months, as assessed by the portion of BSPE tests showing a positive or negative shift in sensation
BSPE sensory shifts at Month 12:
Analysis was performed on the number of tests, not the number of patients
BSPE changes over timeTo assess whether repeated HCCTS + SOC is associated with improvement or normalizationa in sensory function over time
BSPE shifts over time:
Analysis was performed on the number of tests, not the number of patients
Tests were classified as positive shift, negative shift, or shift from below-normal to normala
aNormal sensory function reflects the predefined scoring criteria used in the BSPE and does not represent restoration to healthy control sensory function
Subgroup objective
BSPE and Norfolk QOL-DN sensory function in patients with below-normal sensory function at baselineTo examine changes in sensory function over time in patients receiving repeated HCCTS + SOC versus SOC alone
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. In the PACE study, the Norfolk QOL-DN total score, as well as the small and large-fiber subscales, were analyzed.
In the original Phase 3 PACE study, patients received repeated applications of either 30-minute or 60-minute HCCTS. This post-hoc analysis was restricted to patients treated with 30-minute HCCTS, consistent with the approved duration for PDPN.
aAssessed by BSPE. Normal sensory function reflects the predefined scoring criteria used in the BSPE and does not represent restoration to healthy control sensory function.
QZA-04-26-0014 | July 2026
Footnotes
BSPE, Brief Sensory Pain Examination; HCCTS, high-concentration capsaicin topical system; PDPN, painful diabetic peripheral neuropathy; QOL-DN, Quality of Life–Diabetic Neuropathy; SOC, standard of care.
1. Katz NP et al. Muscle & Nerve. 2026;73:1109–1117.
PACE post-hoc study limitations1
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
Subgroup analyses included relatively small numbers of patients with below-normal sensory function at baseline
The BSPE includes commonly used bedside neurological tests but has not been formally validated to detect clinically meaningful changes in sensory function
The open-label, non-placebo-controlled study design may have introduced bias in interpretation of results
Attrition over time and changes in mobility, medication use, and metabolic control post treatment may have influenced observed sensory outcomes
Click here to view data from the PACE post-hoc analysis
Methods overview
PACE study design1,2
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. Patients randomized to HCCTS plus SOC were eligible for repeated treatment at intervals of ≥8 weeks, for a maximum of 7 treatments.
Adults aged ≥18 years with a diagnosis of PDPN due to T1D/T2D for ≥1 year
N=468 R 1:1:1
N=155
SOC
N=156
HCCTS30-minute application + SOC
N=157
HCCTS60-minuteaapplication + SOC
Clinic visits conducted at months indicated
The study design allowed for HCCTS retreatment at both scheduled and unscheduled clinic visits, provided at least 8 weeks had elapsed since the last treatment
Months
Primary endpoint
Percentage change in total score of Norfolk QOL-DN
Secondary endpoints
UENS assessments
Standardized testing of sensory function and reflex function by BSPE
PGIC
Average pain score, NPRS
Response rates
EQ-5D
The primary PACE study 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
aThe HCCTS is not approved by the FDA as a 60-minute application for DPN, and the safety and effectiveness of this dosage have not been established. The approved dose of HCCTS for DPN is a single, 30-minute application on the feet of up to four topical systems. Treatment may be repeated every 3 months or as warranted by the return of pain (not more frequently than every three months).
BPI, Brief Pain Inventory; BSPE, Brief Sensory Pain Examination; DPN, diabetic peripheral neuropathy; EQ-5D, EuroQol 5-Dimension questionnaire; FDA, Food and Drug Administration; HBA1c, hemoglobin A1c; HCCTS, high-concentration capsaicin topical system; LOCF, Last Observation Carried Forward; NPRS, Numeric Pain Rating Scale; MNSI, Michigan Neuropathy Screening Instrument; PDPN, painful diabetic peripheral neuropathy; PGIC, Patient Global Impression of Change; QOL-DN, Quality of Life–Diabetic Neuropathy; R, randomized; SD, standard deviation; SOC, standard of care; T1D, type 1 diabetes; T2D, type 2 diabetes; QST, Quantitative Sensory Testing; UENS, Utah Early Neuropathy Scale.
1. Katz NP et al. Muscle & Nerve. 2026;73:1109–1117. 2. Vinik AI et al. BMC Neurol. 2016;16:251.
PACE study limitations2
The study’s open-label design, while potentially more representative of clinical practice than a double-blind design, may have introduced bias in safety evaluations, as patients and investigators were aware of the treatment being administered
Although physicians assessing neurological function were blinded, the lack of blinding for patients and investigators could have influenced outcomes
The LOCF imputation method used for missing data is conservative and may have led to worse estimates compared to a non-imputed analysis
Statistical analysis was limited, as p-values were not calculated to complement the 90% confidence intervals for between-group differences
QST was not performed due to lack of standardization and training across study sites, and instead, ‘bedside’ sensory testing was used, which may have reduced sensitivity in detecting subtle sensory changes
The impact of concomitant opioid use on the results was not fully addressed
The predominantly Caucasian study population (99%) may limit the generalizability of findings to patients of other ethnicities
Baseline characteristics1
30-min HCCTS treatment + SOC (n=156)
SOC alone (n=155)
Sex, n (%)
Male
74 (47.4)
71 (45.8)
Female
82 (52.6)
84 (54.2)
Age, years
Mean (SD)
60.9 (10.9)
59.1 (10.3)
Duration of PDPN, years
Mean (SD)
4.1 (3.7)
4.4 (3.6)
Patient eligibility2
Inclusion criteria
Aged ≥18 years
Diagnosis of PDPN confirmed by a score of ≥3 on the MNSI
HbA1c ≤9% (74.9 mmol/mol) at 3–6 months prior to and at screening
Stable glycemia control for ≥6 months prior to screening visit
Average daily pain score over the last 24 h ≥4 (question 5 of BPI-DN) at the screening and the baseline visit
Primary endpoint2
In the PACE study, the percentage change in total score of the Norfolk QOL-DN was used to assess functional consequences of potential small nerve fiber dysfunction that may have been associated with HCCTS repeat treatment and adversely affected QOL
Patients with DPN examined in this post-hoc analysis received repeat HCCTS plus SOC treatment. Patients who received repeat HCCTS experienced:
BSPE sensory shifts at the end of the study
More positive shifts in BSPE scores were seen across all five BSPE stimuli than negative shifts during the 12-month study period
Mean change from baseline to Month 12 in BSPE scores
Statistically significant sensory improvements were observed in heat, vibration, and sharp tests in patients with baseline sensory deficits versus SOC alone
Normalization of sensory function over time
Among those with below-normal sensory function at baseline, the proportion of tests showing normalavalues in heat, cold, and sharp increased with repeated HCCTS treatments
Nerve function outcomes assessed by Norfolk QOL-DN
Statistically significant improvements in patient-reported outcomes related to nerve fiber function versus SOC alone based on Norfolk QOL–DN
aAssessed by BSPE. Normal sensory function reflects the predefined scoring criteria used in the BSPE and does not represent restoration to healthy control sensory function.
QZA-04-26-0014 | July 2026
Footnotes
BSPE, Brief Sensory Pain Examination; DPN, diabetic peripheral neuropathy; HCCTS, high-concentration capsaicin topical system; QOL-DN, Quality of Life–Diabetic Neuropathy; SOC, standard of care.
1. Katz NP et al. Muscle & Nerve. 2026;73:1109–1117.
BSPE sensory shifts at the end of the study
chart placeholder — BSPE sensory shift data
Mean change from baseline to Month 12 in BSPE scores
chart placeholder — mean BSPE change to Month 12
Normalization of sensory function over time
chart placeholder — normalization over time
Nerve function outcomes assessed by Norfolk QOL-DN
BSPE sensory shifts at the end of the 12-month study1
Proportion of tests showing shift, %
35302520151050
Analysis was performed on the number of tests, not the number of patients; n=156 patients who received 30-min application of HCCTS + SOC. Only descriptive analyses performed (no statistical analyses).
Summary
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
QZA-04-26-0014 | July 2026
Footnotes
BSPE, Brief Sensory Pain Examination; HCCTS, high-concentration capsaicin topical system; QOL-DN, Quality of Life–Diabetic Neuropathy; SOC, standard of care.
1. Katz NP et al. Muscle & Nerve. 2026;73:1109–1117.
Mean change from baseline to Month 12 in BSPE scores1
Summary
In patients with baseline sensory deficits, statistically significant improvements in BSPE scores versus SOC alone were observed for heat sensation (p=0.009), vibration sensation (p=0.008), and sharp sensation (p=0.048)
Changes in cold sensation and deep tendon reflexes were not statistically significant versus SOC alone
QZA-04-26-0014 | July 2026
Footnotes
BSPE, Brief Sensory Pain Examination; CI, confidence interval; HCCTS, high-concentration capsaicin topical system; NS, not significant; SOC, standard of care.
1. Katz NP et al. Muscle & Nerve. 2026;73:1109–1117.
Normalization of sensory function over time following repeated 30-min HCCTS treatments + SOC1
Proportion of tests showing a shift to normal, %
100806040200
Analysis was performed on the number of tests, not the number of patients. Only descriptive analyses performed (no statistical analyses).
Summary
Among tests of heat, cold, and sharp stimuli that showed below-normal sensation at baseline, the proportion showing normal sensation increased with repeated HCCTS treatments
For tests of vibration and deep tendon reflex that were below-normal at baseline, moderate increases in the proportion showing normal sensation were observed with repeated HCCTS treatments
QZA-04-26-0014 | July 2026
Footnotes
BSPE, Brief Sensory Pain Examination; HCCTS, high-concentration capsaicin topical system; QOL-DN, Quality of Life–Diabetic Neuropathy; SOC, standard of care.
1. Katz NP et al. Muscle & Nerve. 2026;73:1109–1117.
Nerve function outcomes assessed by Norfolk QOL-DN
Norfolk QOL-DN total score
Aggregate score across nerve function, symptoms, and activities of daily living
Norfolk QOL-DN subscales
Small fiber function
Large fiber function
Summary
The Norfolk QOL-DN questionnaire assesses changes in nerve function and the overall impact of nerve fiber dysfunction on QOL, daily activities, and health
Among patients with below-normal sensory function at baseline, statistically significant improvements in patient-reported outcomes related to nerve fiber function were observed in the Norfolk QOL-DN total score (p<0.001) and the Norfolk QOL-DN large-fiber subscale (p<0.001) versus SOC
Changes in the Norfolk QOL-DN small-fiber subscale were not statistically significant
QZA-04-26-0014 | July 2026
Footnotes
BSPE, Brief Sensory Pain Examination; CI, confidence interval; HCCTS, high-concentration capsaicin topical system; QOL-DN, Quality of Life–Diabetic Neuropathy; SOC, standard of care.
1. Katz NP et al. Muscle & Nerve. 2026;73:1109–1117.
Patients with below-normal sensation experienced statistically significant improvements in Norfolk QOL-DN total score (p<0.001)
No statistically significant between-group difference was seen in Norfolk QOL-DN small-fiber subscale score
Patients with below-normal sensation experienced statistically significant improvements in Norfolk QOL-DN large fiber score (p<0.001)
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