Study of the Efficacy, Safety, and Tolerability of Serlopitant for the Treatment of Chronic Pruritus of Unknown Origin

Study Overview
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Brief Summary
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A Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy, Safety, and Tolerability of Serlopitant for the Treatment of Chronic Pruritus of Unknown Origin

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy, Safety, and Tolerability of Serlopitant for the Treatment of Chronic Pruritus of Unknown Origin

Conditions
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Pruritus

Intervention / Treatment
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* Drug: 5 mg Serlopitant Tablets
* Drug: Matching Placebo Tablets


Participation Criteria
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Eligibility Criteria
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Inclusion: Male or female, age 18 years or older at consent. The subject must have ongoing chronic pruritus The subject's pruritus is assessed by the investigator to be of unknown origin at baseline. Worst-Itch Numeric Rating Scale (WI-NRS) score in the 24-hour period prior to the Screening visit, and average weekly WI-NRS score in each of the 2 weeks prior to Baseline visit indicating an appropriate pruritus level for the study. The pruritus must have been unresponsive to prior treatment with emollients. The subject's pruritus must be present on multiple segments of the body Willing and able to complete daily eDiary entries within a consistent timeframe for the duration of the study All females who are of childbearing potential must be willing to practice highly effective contraception and not be pregnant or nursing Willing to comply with study visits and study related requirements including providing written informed consent. Adequate cognitive and physical ability, in the investigator's opinion, to comply with study visits and study related requirements including providing written informed consent Exclusion Prior treatment with any NK1-receptor antagonists Known dermatologic or systemic condition(s), other than dry skin, that is considered by the investigator to be the primary cause of current pruritus. Untreated or inadequately treated thyroid, adrenal, or pituitary disease or nodules, or history of thyroid malignancy. Use of an excluded therapy within 3 weeks prior to randomization Treatment with any investigational therapy within 3 weeks prior to randomization. Serum creatinine, total bilirubin, alanine aminotransferase or aspartate aminotransferase > 2.5 times the upper limit of normal during screening. History of malignancy within 3 years prior to randomization, with the (actinic keratosis, non-metastatic cutaneous squamous cell carcinoma, basal cell carcinoma of skin). Any known major psychiatric diagnosis that would impact the subject's ability to complete the study Suicidal ideation within 3 years prior to randomization, or any history of suicide attempt. Known use of recreational drugs. Documented history of parasitic infection, including skin parasites such as scabies, within 12 weeks prior to randomization. Presence of clinically significant dementia, intellectual impairment, or any medical condition or disability that, in the investigator's opinion, could interfere with the assessment of safety or efficacy in this trial or compromise the safety of the subject. History of hypersensitivity to serlopitant or any of its components. Planned or anticipated major surgical procedure or other activity that would interfere with the subject's ability to comply with protocol-mandated assessments (e.g. extended international travel) during the subject's participation in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5 mg Serlopitant Tablets<br>Serlopitant Tablets | Drug: 5 mg Serlopitant Tablets<br>* Serlopitant Tablets<br>* Other names: VPD-737;|
| Placebo Comparator: 5 mg Placebo Tablets<br>Placebo Tablets | Drug: Matching Placebo Tablets<br>* Placebo Tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Worst Itch Numeric Rating Scale 4-point Responder Rate at Week 10 | During the study, Worst Itch Numeric Rating Scale (WI-NRS) assessments was reported by the subject via eDiary. The daily NRS results were summarized. The daily results were averaged to create weekly measures. The Itch NRS is a validated, self-reported, instrument for measurement of itch intensity. It used a 24-hour recall period and asked subjects to rate the intensity of their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable), higher scores indicated greater itch intensity. A subject was a 4-point responder if their change from baseline is ≤ -4 (i.e. a decrease of at least 4). | At Week 10 | 
| WI-NRS 4-point Responder Rate at Weeks 2 4, 6, and 8 | During the study, Worst Itch Numeric Rating Scale (WI-NRS) assessments was reported by the subject via eDiary. The daily NRS results were summarized. The daily results were averaged to create weekly measures. The Itch NRS is a validated, self-reported, instrument for measurement of itch intensity. It used a 24-hour recall period and asked subjects to rate the intensity of their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable), higher scores indicated greater itch intensity. A subject was a 4-point responder if their change from baseline is ≤ -4 (i.e. a decrease of at least 4). | At Weeks 2, 4, 6, and 8 | 
| WI-NRS 3-point Responder Rate at Weeks 2, 4, 6, 8, and 10 | During the study, Worst Itch Numeric Rating Scale (WI-NRS) assessments was reported by the subject via eDiary. The daily NRS results were summarized. The daily results were averaged to create weekly measures. The Itch NRS is a validated, self-reported, instrument for measurement of itch intensity. It used a 24-hour recall period and asked subjects to rate the intensity of their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable), higher scores indicated greater itch intensity. A subject was a 3-point responder if their change from baseline is ≤ -3 (i.e. a decrease of at least 3). Results presented below is of subjects who were a 3-point responder but not a 4-point responder. | At Weeks 2, 4, 6, 8, and 10 | 
| Change From Baseline in WI-NRS at Weeks 2, 4, 6, 8, and 10 | During the study, Worst Itch Numeric Rating Scale (WI-NRS) assessments was reported by the subject via eDiary. The daily NRS results were summarized. The daily results were averaged to create weekly measures. The Itch NRS is a validated, self-reported, instrument for measurement of itch intensity. It used a 24-hour recall period and asked subjects to rate the intensity of their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable), higher scores indicated greater itch intensity. | At Weeks 2, 4, 6, 8, and 10 | 
| Change From Baseline in Daily WI-NRS Scores Through Week 2 | During the study, Worst Itch Numeric Rating Scale (WI-NRS) assessments was reported by the subject via eDiary. The daily NRS results were summarized. The daily results were averaged to create weekly measures. The Itch NRS is a validated, self-reported, instrument for measurement of itch intensity. It used a 24-hour recall period and asked subjects to rate the intensity of their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable), higher scores indicated greater itch intensity. | Through 2 weeks | 
| Change From Baseline in Worst-Itch Visual Analog Scale at Weeks 2, 4, 6, and 10 | The Itch Visual Analog Scale (VAS) is a validated, self-reported instrument for measurement of itch intensity. It used a 24-hour recall period and asked subjects to rate the worst intensity of their itch on a 100-mm horizontal line ranging from 0 mm (no itch) to 100 mm (worst itch imaginable). Higher scores indicated greater itch intensity. The VAS measurement were summarized in centimeters. WI-VAS assessments were reported by the subject via a paper form administered at study visits. | At Weeks 2, 4, 6, and 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Adverse events (AEs) were recorded to assess the safety and tolerability of repeated oral doses of serlopitant in adult subjects with chronic pruritus of unknown origin. Adverse events (AEs) and SAEs were recorded from the first study drug administration through the follow-up visit. After informed consent was signed, but prior to initiation of study drug, only SAEs considered by the investigator to be caused by a protocol-mandated intervention were collected. | From screening until the Follow-up (F/U) visit which occurred 35 days (+ 7 days) after the Week 10 visit or the last dose of study drug for subjects who discontinued study drug early. | 
| Plasma Concentrations of Serlopitant and Metabolites | The plasma concentrations of serlopitant and metabolites were combined with the data from other serlopitant clinical studies for population pharmacokinetic analysis. | At Week 10 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pruritus