Serlopitant for the treatment of chronic pruritus: Results of a randomized, multicenter, placebo-controlled phase 2 clinical trial

Abstract

Background: The substance P/neurokinin 1 receptor pathway is critical in chronic pruritus; anecdotal evidence suggests that antagonism of this pathway can reduce chronic itch.

Objective: To assess the safety and efficacy of the substance P/neurokinin 1 receptor antagonist serlopitant in treating chronic pruritus.

Methods: Eligible patients with severe chronic pruritus who were refractory to antihistamines or topical steroids were randomized to serlopitant, 0.25, 1, or 5 mg, or to placebo, administered once daily for 6 weeks as monotherapy or with midpotency steroids and emollients. The primary efficacy end point was percentage change in visual analog scale pruritus score from baseline.

Results: Serlopitant treatment resulted in a dose-dependent decrease in pruritus. The mean percentage decreases from baseline visual analog scale pruritus scores were statistically significantly larger with the 1- and 5-mg doses of serlopitant (P = .022 and P = .013, respectively) than with placebo at week 6. No significant safety or tolerability differences were detected among the groups.

Limitations: The sample size was insufficient for subgroup analyses of the efficacy of serlopitant for chronic pruritus on the basis of underlying conditions.

Conclusions: Serlopitant, 1 mg and 5 mg daily, was associated with a statistically significant reduction in chronic pruritus and was well tolerated (NCT01951274).

Keywords: NK1 receptor; NK1 receptor antagonist; chronic pruritus; itch; neurokinin 1 receptor; serlopitant; substance P.