Novel TRPM8 Agonist Cooling Compound Against Chronic Itch: Results from a Randomized, Double-blind, Controlled, Pilot Study in Dry Skin

BACKGROUND: Patients suffering from chronic pruritus (CP) due to dry skin with are often applying emollients containing menthol. However, topical menthol may be irritating and of weak potency in severe pruritus. Two TRPM8 agonists, (1R,2S,5R)-N-(2-(2-pyridinyl)ethyl)-2-ispropyl-5-methylcyclohexancarboxamide and menthoxypropanediol, combined as cooling compound (CC) have shown stronger activation of TRPM8 than menthol.

OBJECTIVES: Objective of this study was to evaluate the efficacy and safety of CC in alleviating pruritus in patients with dry itchy skin.

METHODS: In this vehicle-controlled, double-blind, randomized (1 : 1) study, 70 dry skin patients with pruritus intensity measured by Numerical Rating Scale (NRS) ≥3, were treated twice daily over 4 weeks, either with a lotion containing CC or with its vehicle.

RESULTS: At treatment end, pruritus, assessed by a global score, improved significantly more in the CC than in the vehicle group (79.2% vs. 47.1%; P < 0.05; primary endpoint). Also assessed by verbal rating scale (VRS) and percentual improvement, pruritus decreased significantly more in the CC group (P = 0.007/P = 0.015) compared to vehicle arm after treatment. Up to 84% of CC-treated patients reported a significant, sometimes too strong, long-lasting cooling effect. The health-related quality of life improved significantly more in the CC group (P = 0.023). Skin roughness, dryness and hydration improved significantly in both groups without significant differences in-between them. There were no severe adverse events reported.

CONCLUSIONS: Treatment of dry and pruritic skin with a lotion containing the TRPM8 agonist combination ameliorates severe pruritus and represents a possible novel treatment for the burdensome symptom. The most suitable treatment concentration needs still to be identified. ClinicalTrials.gov: NCT00669708.