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The following is a summary of “Topically applied novel TRPV1 receptor antagonist, ACD440 Gel, reduces evoked pain in healthy volunteers, a randomized, double-blind, placebo-controlled, crossover study,” published in the June 2024 issue of Pain by Segerdahl, et al.

While TRPV1 is crucial for pain perception, prior attempts to create oral TRPV1 blockers were abandoned due to unwanted side effects like widespread heat indifference and body temperature regulation issues.

Researchers conducted a retrospective study accessing healthy volunteers with effectiveness, safety, and blood presence with topical TRPV1-antagonist gel (ACD440 gel).

They conducted a study in two parts. In part 1, 24 healthy subjects participated in a randomized double-blind, placebo-controlled, crossover trial. The ACD440 Gel or placebo was applied once daily and wiped off after 1 hour, for 5 consecutive days. Assessments were performed on normal skin, skin optimized for penetration (by stripping and occlusive gel application), and UVB-irradiated skin. Pain induced by thermo-nociceptive CO₂ laser impulses generated laser-evoked potentials (LEPs), with readouts of peak-to-peak (PtP) amplitude in vertex-EEG and pain assessments by VAS (0–100). Endpoints included effects at 1-hour post-dose, AUC (Days 1–5), and AUC _{(0–24, Day 4)}. In UVB-irradiated skin, pain on pinpricks and skin redness were also assessed. Part 2 examined the plasma pharmacokinetics of ACD440.

The results showed that ACD440 Gel significantly reduced LEP- PtP amplitude and visual analog scale (VAS) pain (P<0.001) in all skin conditions, compared to placebo. In UVB-irradiated skin, pinprick pain also decreased (P=0.047). Effects were significant after 1 hour, lasting at least 9 hours. No AEs or drug-induced erythema occurred. Plasma exposures of ACD440 were too low to determine an elimination half-life of ACD440.

Investigators found topical ACD440 gel effectively reduced LEP, VAS scores, and pinprick pain with minimal systemic exposure, warranting further development.

Source: onlinelibrary.wiley.com/doi/full/10.1002/ejp.2299