Capsaicin 8% patch in painful diabetic peripheral neuropathy: A randomized, double-blind, placebo-controlled study

Contributors:

Simpson DM, Robinson-Papp J, Van J et al.

Name of journal:

Journal of Pain

VIEW PUBLICATION

DOI:

doi:10.1016/j.jpain.2016.09.008

Topics:

DPN STEP Phase 3 Peripheral neuropathic pain Randomized controlled trial Capsaicin 8% topical system

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Summary

This page provides a summary of Simpson DM et al. J Pain. 2017;18(1):42–53. It is a simplified representation of the key points that was created by Averitas Pharma, and should not be considered a replacement for the full article or its abstract. Please refer to the original publication for further details and disclosures.

STEP study: Evaluating the efficacy and safety of a single 30-minute application of capsaicin 8% topical system against placebo in patients with painful diabetic peripheral neuropathy of the feet¹

Background

Painful diabetic peripheral neuropathy is a debilitating complication commonly experienced by people with diabetes and results from dysfunction of peripheral nerve fibers.¹ Oral pharmacological agents, such as antidepressants, anticonvulsants, or opioid medications, are often used for managing neuropathic pain.¹ These treatments act on the central nervous system and are associated with some limitations, including systemic adverse events (AEs), drug-drug interactions, and the need for dose titration.¹

STEP was the first trial to assess the efficacy and safety of capsaicin 8% topical system (previously known as capsaicin 8% patch) in patients with painful diabetic peripheral neuropathy.¹ The capsaicin 8% topical system leverages a matrix technology that enables rapid delivery of high concentration capsaicin directly to the skin.^1,2 It acts locally on pain sensing (nociceptive) nerve fibers through selective binding to transient receptor potential vanilloid 1 (TRPV1) channels, which are overexpressed on such fibers.^1,2 Systemic absorption of capsaicin from the topical system is minimal, thereby limiting the potential for drug-drug interactions, eliminating the need for dose adjustments in special populations and minimizing the risk of systemic AEs.¹

Peripheral nerve fiber dysfunction and neuropathic pain of the feet in painful diabetic peripheral neuropathy

Aim

STEP was a phase 3, randomized, double-blind, placebo-controlled, multicenter trial evaluating the efficacy and safety of a single 30-minute application of capsaicin 8% topical system against placebo over 12 weeks in patients with painful diabetic peripheral neuropathy of the feet (ClinicalTrials.gov Identifier: NCT01533428).¹

Application of capsaicin 8% topical system on the foot of a patient with painful diabetic peripheral neuropathy of the feet

Key findings

Patients with painful diabetic peripheral neuropathy of the feet who were treated with the capsaicin 8% topical system experienced modest and statistically significant improvements in pain relief compared to those treated with an identical placebo topical system¹

Patients assessed their average daily pain over the previous 24 hours with the numerical pain rating scale (NPRS) using question 5 of the Brief Pain Inventory-Diabetic Neuropathy (BPI-DN) questionnaire.¹

From baseline to mean pain score from Week 2 through 8 (primary endpoint), there was a modest and statistically significant reduction in average daily pain score (p=0.025) for patients using capsaicin 8% topical system (–27.4%, n=186) versus placebo (–20.9%, n=183)¹
Analysis of change in mean pain score from baseline to Week 2 through 12 (secondary endpoint) showed that this reduction in pain was maintained (p=0.018) for patients using capsaicin 8% topical system (–28.0%) versus placebo (–21.0%)¹
The median time-to-treatment response was shorter for patients treated with capsaicin 8% topical system versus placebo, with 50% of patients achieving ≥30% reduction in average daily pain by Day 19 (95% CI 12.0–37.0) in the capsaicin 8% topical system group versus Day 72 with placebo (95% CI 19.0–not calculable)¹

Pain reduction in patients with painful diabetic peripheral neuropathy of the feet

Sleep interference improved with capsaicin 8% topical system treatment versus placebo¹

The mean percentage reduction from baseline in BPI-DN NPRS score for sleep interference (secondary endpoint) was significantly greater for patients treated with the capsaicin 8% topical system versus placebo throughout the study (p=0.030 from baseline to Week 2–8; p=0.020 from baseline to Week 2–12).¹

Treatment-emergent adverse events (TEAEs) were more frequent in the capsaicin 8% topical system group (46.8%) than in the placebo group (33.9%)¹

This difference was primarily attributable to application-site reactions (33.9% with capsaicin versus 8.2% with placebo).¹

Assessment of changes in sensory perception and reflex testing indicated that most patients experienced either no change or an improvement from baseline through Week 12.¹ No indications of deterioration in sensory perception of sharp, cold, warm, or vibration stimuli were observed.¹

Conclusions

Treatment with capsaicin 8% topical system in patients with painful diabetic peripheral neuropathy of the feet resulted in modest and statistically significant pain relief, and improved sleep quality versus placebo.¹

The capsaicin 8% topical system was well tolerated and was not associated with any sensory deterioration or new safety concerns.¹

Limitations

Study limitations include potential functional unblinding due to application-site reactions in the capsaicin 8% topical system group, though the impact could not be quantified because no final masking assessment was performed.¹ Despite showing statistical superiority over placebo (p=0.025) in the primary analysis, the treatment effect was modest, necessitating careful evaluation of clinical relevance for individual patients.¹ Methodological constraints restricted assessments to “bedside” sensory testing, as implementing full Quantitative Sensory Testing across multiple centers was impractical due to training and standardization challenges, potentially limiting detection of subtle sensory changes.¹ Additionally, the 12-week duration and evaluation of a single treatment prompted a separate 52-week open-label study (PACE study) to assess long-term safety and tolerability (primary endpoint) and efficacy of repeated treatments.¹

Information updated in March 2025.

Indication

In the USA, capsaicin 8% topical system is indicated in adults for the treatment of neuropathic pain associated with postherpetic neuralgia (PHN) or associated with diabetic peripheral neuropathy (DPN) of the feet.

Select Important Safety Information

Capsaicin 8% topical system must be administered only by healthcare professionals on dry, intact skin, following safety protocols to prevent severe irritation, burns, and pain. Capsaicin may cause severe irritation with unintended capsaicin exposure. Patients may experience severe application-associated pain, increased blood pressure, temporary changes in sensory function, and severe application-site burns, requiring careful monitoring, protective measures, and adherence to dosing and administration, and disposal guidelines. The most common adverse reactions in all controlled clinical trials are application-site erythema, application-site pain, and application-site pruritus. For more detailed information, please see full prescribing information.

For more detailed information, please see

Full Prescribing Information

Capsaicin 8% patch in painful diabetic peripheral neuropathy: A randomized, double-blind, placebo-controlled study