A randomized, multicenter, double-blind, placebo-controlled Phase II clinical trial of serlopitant for the treatment of chronic pruritus
Presenters: Ständer S1, Yosipovitch G2, Kerby MB3, Larrick JW4, Perlman AJ4, Schnipper EF4, Zhang X3, Tang JY5, Luger TA2, Steinhoff M6,7
Affiliation: 1Center for Chronic Pruritus, Department of Dermatology, University Hospital Münster, Münster, Germany; 2Miami Itch Center, Department of Dermatology and Cutaneous Surgery Miller School of Medicine, University of Miami, Miami, FL; 3Menlo Therapeutics Inc, Redwood City, CA; 4Velocity Pharmaceutical Development, LLC, San Francisco, CA, USA; 5Department of Clinical Dermatology, Stanford University, Stanford, CA; 6Department of Dermatology and UCD Charles Institute of Translational Dermatology, University College Dublin, Dublin, Ireland; 7Department of Dermatology, University of California San Diego, San Diego, CA
Background/Objective: Chronic pruritus, a common debilitating symptom of many conditions, can result in significant morbidity and impaired quality of life. Inadequate itch relief or undesirable safety and tolerability issues have been associated with many of the current therapies. The neuropeptide substance P and its receptor neurokinin 1 receptor (NK1R) play important roles in pruritus signaling. The potent, highly selective, brain-permeable, oral NK1R antagonist serlopitant is currently under investigation for the treatment of chronic pruritus and other conditions. Here, we report the efficacy and safety results from a Phase II clinical trial of once-daily oral serlopitant versus placebo for the treatment of chronic pruritus (ClinicalTrials.gov ID, NCT01951274).
Methods: Key eligibility criteria included pruritus lasting at least six weeks that was nonresponsive or inadequately responsive to treatment with topical steroids or antihistamines and a baseline Visual Analog Scale (VAS) pruritus score of at least 7cm. Patients were randomized 1:1:1:1 to receive serlopitant 0.25mg, 1mg, 5mg, or placebo. After a loading dose of three tablets at baseline, patients took one tablet daily at bedtime for six weeks. The primary efficacy endpoint was the VAS pruritus score percentage change from baseline. Secondary pruritus measures included the Numeric Rating Scale (NRS), Subject’s Global Assessment of itch, patient responses to the Dermatology Life Quality Index and Pittsburgh Sleep Symptom Questionnaire- Insomnia questionnaires, and the Physician’s Global Assessment. Adverse events (AEs) and clinical and laboratory assessments were evaluated during treatment and follow-up. Change from baseline itch intensity as measured by the VAS and NRS score was analyzed in the intent-to-treat population, and the difference in average change from baseline between the serlopitant and placebo groups was tested using a t-test without control for multiplicity. Primary and secondary efficacy endpoints used an alpha value of p<0.05.
Results: A total of 257 patients were randomized to serlopitant 0.25mg (n=64), 1mg (n=65), or 5mg (n=64) or placebo (n=64); baseline characteristics were comparable between groups. Differences in percentage change from baseline itch VAS score were statistically significantly greater with serlopitant versus placebo for serlopitant 1mg at Weeks 3, 4, 5, and 6 and 5mg at Weeks 4, 5, and 6. Statistically significant improvements in severity of itch from baseline were also demonstrated using the NRS with serlopitant 1mg and 5mg at Weeks 4, 5, and 6 (p?0.05) compared with placebo. The most common treatment-emergent adverse events (TEAEs) in the serlopitant groups were somnolence (1.6%, 4.6%, and 4.7% for serlopitant 0.25mg, 1mg, and 5mg, respectively, and 1.6% for placebo) and diarrhea (0%, 6.2%, and 3.1% for serlopitant 0.25mg, 1mg, and 5mg, respectively, and 1.6% for placebo). Most TEAEs were of mild or moderate intensity. There were no meaningful trends in laboratory abnormalities or changes in vital signs, and no deaths.
Conclusion: Serlopitant 1mg and 5mg provided statistically significant reductions in pruritus intensity compared with placebo. Serlopitant was well tolerated. Almost all TEAEs were of mild or moderate intensity, and no meaningful adverse safety trends were observed in this study.