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

  • J Am Acad Dermatol. 2018 May;78(5):882-891.e10. doi: 10.1016/j.jaad.2018.02.030.
Gil Yosipovitch  1 ,  Sonja Ständer  2 ,  Matthew B Kerby  3 ,  James W Larrick  4 ,  Andrew J Perlman  4 ,  Edward F Schnipper  4 ,  Xiaoming Zhang  3 ,  Jean Y Tang  5 ,  Thomas Luger  6 ,  Martin Steinhoff  7
Affiliations
  • 1. Miami Itch Center, Department of Dermatology and Cutaneous Surgery, Miller School of Medicine, University of Miami, Miami, Florida.
  • 2. Center for Chronic Pruritus, Department of Dermatology, University Hospital Münster, Münster, Germany.
  • 3. Menlo Therapeutics Inc, Redwood City, California.
  • 4. Velocity Pharmaceutical Development, LLC, South San Francisco, California.
  • 5. Department of Clinical Dermatology, Stanford University, Redwood City, Stanford, California.
  • 6. Department of Dermatology, University Hospital Münster, Münster.
  • 7. Department of Dermatology, University of California San Diego, Dublin; Department of Dermatology, Weill Cornell University-Qatar, Hamad Medical Corporation, Doha, Qatar. Electronic address: [email protected].
PMID: 29462657 DOI: 10.1016/j.jaad.2018.02.030
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.
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