155: Safety and tolerability of capsaicin (179 mg/ 8%) patch in Post Surgical Neuropathic Pain (RISE)

Topic: Clinical Science
Subtopic: Pain category (ICD-11), Chronic neuropathic pain, Pharmacological treatments, Drug development, Treatment/management

Background and Aims: Post-surgical neuropathic pain (PSNP) is a serious health concern with ≥ 300 million surgical interventions/year worldwide of which ~10% result in chronic pain including 33-68% with neuropathic features. It causes disability, reduced quality of life and increased use of health care resources [1].
Guidelines for peripheral neuropathic pain (PNP) recommending use of α2δ-ligands, SNRIs and TCAs are usually followed for PSNP treatment. These treatments may be associated with tolerability limitations [2], restrictions for use in special populations and drug-drug interactions. Topical approaches without systemic exposure may be preferred especially if the area affected is small as in PSNP.
High-concentration capsaicin (179 mg/8%) patch (HCCP) is a topical treatment applied to the area affected by neuropathic pain. It releases capsaicin, a selective transient receptor potential vanilloid 1 (TRPV1) agonist providing analgesia via temporary neurolysis of nociceptive nerves [3,4]
Safety/tolerability data from a randomized controlled trial (RCT) are presented.

Methods: RISE is a multicenter, RCT, double-blind, parallel-group trial in which adults with PSNP were randomly assigned to 60-minute HCCP versus low-dose capsaicin 0.04% control patch (CTR). The trial included a screening phase (≤19 days), blinded core phase (CORE; Day 1–Week 12), and blinded extension phase (EXT; Weeks 13–42; re-application ≥8-week intervals; last application ≤ week 40). Re-applications were optional and the maximum number of treatments a patient could receive was 5.
As expected by its mode of action, releasing high concentration of capsaicin at the treatment area, HCCP’s safety profile is characterized by transient, mostly mild to moderate application site (AS) reactions. Based on this knowledge, key safety parameters, assessed during clinic visits, included treatment emergent adverse events (TEAEs), vital signs, dermal assessment and neurological/sensory examination. All safety data were summarized by treatment group. No statistical tests were performed.

Results: Treated: 198 (HCCP)/211 (CTR). Mean (range) age: 53.1 (19-84) years; female: 72.1%; mean (SD) treatment area size: 178.5 (174.75) cm2. 25.8%, 14.6%, 12.6%, 26.8% and 20.2% received 1,2,3,4 or 5 HCCP treatments/similar rates in CTR.
519 TEAEs with HCCP (63.1% of patients); 309 with CTR (54.5% of patients). Most TEAEs: mild or moderate; severe TEAEs occurred in 9.1% of HCCP patients (23 events)/3.8% of CTR patients(12 events). Most frequently reported TEAEs (events/% of patients): AS pain (HCCP: 113/27.3%; CTR: 20/6.6%), AS erythema (HCCP: 69 /14.1%; CTR: 23/5.2%). No serious HCCP-related TEAEs occurred. In CORE 55.1% HCCP patients and 37.4% CTR patients experienced any TEAE versus 41.7% and 36.2% respectively in EXT. No clinically relevant vital signs changes.
No irritation on dermal assessment upon first IMP removal in 30.8% (HCCP)/70.1% (CTR), 47.5% (upon 5th HCCP); stable with repeat CTR.
Overall, no sensory function deterioration observed.

Conclusions: The safety profile of HCCP was consistent with prior experience, with most TEAEs being transient, mild or moderate, application site reactions. There were no notable findings in vital signs. Dermal and neurological/sensory findings stayed stable upon repeated treatment. No new safety signals have arisen from this trial, and no new safety findings were identified with repeated treatments.

References: 1. Schug SA, Lavand'hommtrial,Barke A, Korwisi B, Rief W, Treede RD; IASP Taskforce for the Classification of Chronic Pain. The IASP classification of chronic pain for ICD-11: chronic postsurgical or posttraumatic pain. Pain. 2019 Jan;160(1):45-52.
2. Lavand’homme P. Transition from acute to chronic pain after surgery. Pain. 2017b; 158: 50–54.
3. Perry T, editor. Therapeutics Letter. Vancouver (BC): Therapeutics Initiative; 1994-. Letter 96, Benefits and harms of drugs for “neuropathic” pain. 2015 Oct. Available from: https://www.ncbi.nlm.nih.gov/books/NBK598505/

Presenting Author: Mariana Napoles
Submitting Author: Marielle Eerdekens

Senior Author: Mark S. Wallace

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• Mark S. Wallace: MC - UC San Diego Health, San Diego, CA, USA
• Johannes Mouton: MBChb, PhD - Grünenthal GmbH
• Mariana Napoles: PhD - Grünenthal Ltd
• Heiko Hagedorn: PhD - Grünenthal GmbH
• Marie-Henriette Eerdekens: MD, MBA - Grünenthal GmbH
• Samuel Allen: PhD - Averitas Pharma Inc
• Lizandra P. Marcondes: MD, PhD - Averitas Pharma Inc