Pruritus
Conditions
Keywords
Pruritus
Brief summary
A Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy, Safety, and Tolerability of Serlopitant for the Treatment of Chronic Pruritus of Unknown Origin
Interventions
Serlopitant Tablets
Placebo Tablets
Sponsors
Vyne Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Worst-Itch Visual Analog Scale at Weeks 2, 4, 6, and 10 | 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. |
| Change From Baseline in WI-NRS at Weeks 2, 4, 6, 8, and 10 | 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. |
| Change From Baseline in Daily WI-NRS Scores Through Week 2 | Through 2 weeks | 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. |
| Worst Itch Numeric Rating Scale 4-point Responder Rate at Week 10 | 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). |
| WI-NRS 4-point Responder Rate at Weeks 2 4, 6, and 8 | 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). |
| WI-NRS 3-point Responder Rate at Weeks 2, 4, 6, 8, and 10 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Concentrations of Serlopitant and Metabolites | At Week 10 | The plasma concentrations of serlopitant and metabolites were combined with the data from other serlopitant clinical studies for population pharmacokinetic analysis. |
| Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | 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. | 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. |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 41 sites in US from 22 January 2019 to 21 January 2020. All subjects who met the study entry criteria were randomized in a 1:1 ratio to receive daily oral doses of serlopitant 5 mg or placebo.
Pre-assignment details
During the screening period (3 weeks), all subjects were evaluated for eligibility and assessed for conditions associated with chronic pruritus. Subjects were to complete an electronic diary (eDiary) at the Screening visit.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Randomized subjects received daily oral doses of placebo following an initial 3-tablet loading dose on Day 1. Starting on Day 2, subjects took 1 tablet per day until the completion of the 10-week treatment period. | 117 |
| Serlopitant 5 mg Randomized subjects received daily oral doses of serlopitant 5 mg following an initial 3-tablet loading dose on Day 1. Starting on Day 2, subjects took 1 tablet per day until the completion of the 10-week treatment period. | 116 |
| Total | 233 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 5 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 9 |
Baseline characteristics
| Characteristic | Total | Serlopitant 5 mg | Placebo |
|---|---|---|---|
| Age, Continuous | 59.4 years STANDARD_DEVIATION 12.89 | 60.7 years STANDARD_DEVIATION 13.6 | 58.1 years STANDARD_DEVIATION 12.05 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 22 Participants | 7 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 197 Participants | 102 Participants | 95 Participants |
| Sex: Female, Male Female | 176 Participants | 83 Participants | 93 Participants |
| Sex: Female, Male Male | 57 Participants | 33 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 117 | 0 / 116 |
| other Total, other adverse events | 1 / 117 | 12 / 116 |
| serious Total, serious adverse events | 0 / 117 | 2 / 116 |
Outcome results
Primary
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.
Time frame: Through 2 weeks
Population: Full Analysis Population: subset of subjects in the randomized population who were dispensed study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Daily WI-NRS Scores Through Week 2 | Change from Baseline at Day 14 | -1.92 score on a scale | Standard Deviation 2.518 |
| Placebo | Change From Baseline in Daily WI-NRS Scores Through Week 2 | Change from Baseline at Day 7 | -1.44 score on a scale | Standard Deviation 2.331 |
| Placebo | Change From Baseline in Daily WI-NRS Scores Through Week 2 | Change from Baseline at Day 3 | -0.94 score on a scale | Standard Deviation 1.788 |
| Placebo | Change From Baseline in Daily WI-NRS Scores Through Week 2 | Change from Baseline at Day 8 | -1.35 score on a scale | Standard Deviation 2.171 |
| Placebo | Change From Baseline in Daily WI-NRS Scores Through Week 2 | Change from Baseline at Day 1 | -0.22 score on a scale | Standard Deviation 0.879 |
| Placebo | Change From Baseline in Daily WI-NRS Scores Through Week 2 | Change from Baseline at Day 9 | -1.53 score on a scale | Standard Deviation 2.21 |
| Placebo | Change From Baseline in Daily WI-NRS Scores Through Week 2 | Change from Baseline at Day 4 | -1.16 score on a scale | Standard Deviation 1.977 |
| Placebo | Change From Baseline in Daily WI-NRS Scores Through Week 2 | Change from Baseline at Day 10 | -1.63 score on a scale | Standard Deviation 2.46 |
| Placebo | Change From Baseline in Daily WI-NRS Scores Through Week 2 | Baseline (observed value) | 8.37 score on a scale | Standard Deviation 0.929 |
| Placebo | Change From Baseline in Daily WI-NRS Scores Through Week 2 | Change from Baseline at Day 11 | -1.73 score on a scale | Standard Deviation 2.333 |
| Placebo | Change From Baseline in Daily WI-NRS Scores Through Week 2 | Change from Baseline at Day 5 | -1.34 score on a scale | Standard Deviation 2.103 |
| Placebo | Change From Baseline in Daily WI-NRS Scores Through Week 2 | Change from Baseline at Day 12 | -1.67 score on a scale | Standard Deviation 2.28 |
| Placebo | Change From Baseline in Daily WI-NRS Scores Through Week 2 | Change from Baseline at Day 2 | -0.85 score on a scale | Standard Deviation 1.836 |
| Placebo | Change From Baseline in Daily WI-NRS Scores Through Week 2 | Change from Baseline at Day 13 | -1.82 score on a scale | Standard Deviation 2.335 |
| Placebo | Change From Baseline in Daily WI-NRS Scores Through Week 2 | Change from Baseline at Day 6 | -1.33 score on a scale | Standard Deviation 2.174 |
| Serlopitant 5 mg | Change From Baseline in Daily WI-NRS Scores Through Week 2 | Change from Baseline at Day 14 | -1.74 score on a scale | Standard Deviation 2.266 |
| Serlopitant 5 mg | Change From Baseline in Daily WI-NRS Scores Through Week 2 | Baseline (observed value) | 8.44 score on a scale | Standard Deviation 0.855 |
| Serlopitant 5 mg | Change From Baseline in Daily WI-NRS Scores Through Week 2 | Change from Baseline at Day 1 | -0.09 score on a scale | Standard Deviation 0.819 |
| Serlopitant 5 mg | Change From Baseline in Daily WI-NRS Scores Through Week 2 | Change from Baseline at Day 2 | -0.69 score on a scale | Standard Deviation 1.264 |
| Serlopitant 5 mg | Change From Baseline in Daily WI-NRS Scores Through Week 2 | Change from Baseline at Day 3 | -0.77 score on a scale | Standard Deviation 1.348 |
| Serlopitant 5 mg | Change From Baseline in Daily WI-NRS Scores Through Week 2 | Change from Baseline at Day 4 | -0.96 score on a scale | Standard Deviation 1.459 |
| Serlopitant 5 mg | Change From Baseline in Daily WI-NRS Scores Through Week 2 | Change from Baseline at Day 5 | -0.99 score on a scale | Standard Deviation 1.495 |
| Serlopitant 5 mg | Change From Baseline in Daily WI-NRS Scores Through Week 2 | Change from Baseline at Day 6 | -1.15 score on a scale | Standard Deviation 1.892 |
| Serlopitant 5 mg | Change From Baseline in Daily WI-NRS Scores Through Week 2 | Change from Baseline at Day 7 | -1.35 score on a scale | Standard Deviation 1.758 |
| Serlopitant 5 mg | Change From Baseline in Daily WI-NRS Scores Through Week 2 | Change from Baseline at Day 8 | -1.35 score on a scale | Standard Deviation 1.746 |
| Serlopitant 5 mg | Change From Baseline in Daily WI-NRS Scores Through Week 2 | Change from Baseline at Day 9 | -1.35 score on a scale | Standard Deviation 1.996 |
| Serlopitant 5 mg | Change From Baseline in Daily WI-NRS Scores Through Week 2 | Change from Baseline at Day 10 | -1.41 score on a scale | Standard Deviation 2.023 |
| Serlopitant 5 mg | Change From Baseline in Daily WI-NRS Scores Through Week 2 | Change from Baseline at Day 11 | -1.69 score on a scale | Standard Deviation 2.211 |
| Serlopitant 5 mg | Change From Baseline in Daily WI-NRS Scores Through Week 2 | Change from Baseline at Day 12 | -1.58 score on a scale | Standard Deviation 2.247 |
| Serlopitant 5 mg | Change From Baseline in Daily WI-NRS Scores Through Week 2 | Change from Baseline at Day 13 | -1.75 score on a scale | Standard Deviation 2.291 |
Primary
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.
Time frame: At Weeks 2, 4, 6, 8, and 10
Population: Full Analysis Population: subset of subjects in the randomized population who were dispensed study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in WI-NRS at Weeks 2, 4, 6, 8, and 10 | Baseline (Observed value) | 8.37 score on a scale | Standard Deviation 0.929 |
| Placebo | Change From Baseline in WI-NRS at Weeks 2, 4, 6, 8, and 10 | Change from Baseline at Week 2 | -1.65 score on a scale | Standard Deviation 2.115 |
| Placebo | Change From Baseline in WI-NRS at Weeks 2, 4, 6, 8, and 10 | Change from Baseline at Week 4 | -2.41 score on a scale | Standard Deviation 2.382 |
| Placebo | Change From Baseline in WI-NRS at Weeks 2, 4, 6, 8, and 10 | Change from Baseline at Week 6 | -2.83 score on a scale | Standard Deviation 2.624 |
| Placebo | Change From Baseline in WI-NRS at Weeks 2, 4, 6, 8, and 10 | Change from Basline at Week 8 | -2.99 score on a scale | Standard Deviation 2.647 |
| Placebo | Change From Baseline in WI-NRS at Weeks 2, 4, 6, 8, and 10 | Change from Baseline at Week 10 | -3.34 score on a scale | Standard Deviation 2.787 |
| Serlopitant 5 mg | Change From Baseline in WI-NRS at Weeks 2, 4, 6, 8, and 10 | Change from Basline at Week 8 | -2.97 score on a scale | Standard Deviation 2.562 |
| Serlopitant 5 mg | Change From Baseline in WI-NRS at Weeks 2, 4, 6, 8, and 10 | Baseline (Observed value) | 8.44 score on a scale | Standard Deviation 0.855 |
| Serlopitant 5 mg | Change From Baseline in WI-NRS at Weeks 2, 4, 6, 8, and 10 | Change from Baseline at Week 6 | -2.94 score on a scale | Standard Deviation 2.495 |
| Serlopitant 5 mg | Change From Baseline in WI-NRS at Weeks 2, 4, 6, 8, and 10 | Change from Baseline at Week 2 | -1.61 score on a scale | Standard Deviation 1.961 |
| Serlopitant 5 mg | Change From Baseline in WI-NRS at Weeks 2, 4, 6, 8, and 10 | Change from Baseline at Week 10 | -3.25 score on a scale | Standard Deviation 2.545 |
| Serlopitant 5 mg | Change From Baseline in WI-NRS at Weeks 2, 4, 6, 8, and 10 | Change from Baseline at Week 4 | -2.46 score on a scale | Standard Deviation 2.349 |
Comparison: At Week 2p-value: 0.440995% CI: [-0.49, 0.57]ANOVA
Comparison: At Week 4p-value: 0.549695% CI: [-0.65, 0.57]ANOVA
Comparison: At Week 6p-value: 0.631195% CI: [-0.78, 0.55]ANOVA
Comparison: At Week 8p-value: 0.0295% CI: [-0.65, 0.69]ANOVA
Comparison: At Week 10p-value: 0.394895% CI: [-0.6, 0.78]ANOVA
Primary
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.
Time frame: At Weeks 2, 4, 6, and 10
Population: Full Analysis Population: subset of subjects in the randomized population who were dispensed study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Worst-Itch Visual Analog Scale at Weeks 2, 4, 6, and 10 | Change from Baseline at Week 2 | -22.96 score on a scale | Standard Deviation 27.425 |
| Placebo | Change From Baseline in Worst-Itch Visual Analog Scale at Weeks 2, 4, 6, and 10 | Change from Baseline at Week 6 | -32.83 score on a scale | Standard Deviation 31.046 |
| Placebo | Change From Baseline in Worst-Itch Visual Analog Scale at Weeks 2, 4, 6, and 10 | Change from Baseline at Week 4 | -27.01 score on a scale | Standard Deviation 28.906 |
| Placebo | Change From Baseline in Worst-Itch Visual Analog Scale at Weeks 2, 4, 6, and 10 | Change from Baseline at Week 10 | -37.64 score on a scale | Standard Deviation 31.613 |
| Placebo | Change From Baseline in Worst-Itch Visual Analog Scale at Weeks 2, 4, 6, and 10 | Baseline (Observed Value) | 82.09 score on a scale | Standard Deviation 10.741 |
| Serlopitant 5 mg | Change From Baseline in Worst-Itch Visual Analog Scale at Weeks 2, 4, 6, and 10 | Change from Baseline at Week 10 | -37.42 score on a scale | Standard Deviation 32.986 |
| Serlopitant 5 mg | Change From Baseline in Worst-Itch Visual Analog Scale at Weeks 2, 4, 6, and 10 | Baseline (Observed Value) | 83.53 score on a scale | Standard Deviation 11.941 |
| Serlopitant 5 mg | Change From Baseline in Worst-Itch Visual Analog Scale at Weeks 2, 4, 6, and 10 | Change from Baseline at Week 2 | -20.52 score on a scale | Standard Deviation 28.825 |
| Serlopitant 5 mg | Change From Baseline in Worst-Itch Visual Analog Scale at Weeks 2, 4, 6, and 10 | Change from Baseline at Week 4 | -28.28 score on a scale | Standard Deviation 29.731 |
| Serlopitant 5 mg | Change From Baseline in Worst-Itch Visual Analog Scale at Weeks 2, 4, 6, and 10 | Change from Baseline at Week 6 | -30.92 score on a scale | Standard Deviation 31.487 |
Comparison: At Week 2p-value: 0.24495% CI: [-4.98, 9.87]ANOVA
Comparison: At Week 4p-value: 0.634995% CI: [-9.2, 6.65]ANOVA
Comparison: At Week 6p-value: 1.9195% CI: [-6.4, 10.23]ANOVA
Comparison: At Week 10p-value: 0.49695% CI: [-8.52, 8.97]ANOVA
Primary
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.
Time frame: At Weeks 2, 4, 6, 8, and 10
Population: Full Analysis Population: subset of subjects in the randomized population who were dispensed study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | WI-NRS 3-point Responder Rate at Weeks 2, 4, 6, 8, and 10 | Responders at Week 4 | 8 Participants |
| Placebo | WI-NRS 3-point Responder Rate at Weeks 2, 4, 6, 8, and 10 | Responders at Week 2 | 6 Participants |
| Placebo | WI-NRS 3-point Responder Rate at Weeks 2, 4, 6, 8, and 10 | Responders at Week 6 | 15 Participants |
| Placebo | WI-NRS 3-point Responder Rate at Weeks 2, 4, 6, 8, and 10 | Responders at Week 8 | 14 Participants |
| Placebo | WI-NRS 3-point Responder Rate at Weeks 2, 4, 6, 8, and 10 | Responders at Week 10 | 13 Participants |
| Serlopitant 5 mg | WI-NRS 3-point Responder Rate at Weeks 2, 4, 6, 8, and 10 | Responders at Week 10 | 16 Participants |
| Serlopitant 5 mg | WI-NRS 3-point Responder Rate at Weeks 2, 4, 6, 8, and 10 | Responders at Week 6 | 10 Participants |
| Serlopitant 5 mg | WI-NRS 3-point Responder Rate at Weeks 2, 4, 6, 8, and 10 | Responders at Week 2 | 6 Participants |
| Serlopitant 5 mg | WI-NRS 3-point Responder Rate at Weeks 2, 4, 6, 8, and 10 | Responders at Week 4 | 14 Participants |
| Serlopitant 5 mg | WI-NRS 3-point Responder Rate at Weeks 2, 4, 6, 8, and 10 | Responders at Week 8 | 15 Participants |
Comparison: At Week 2p-value: 0.495295% CI: [-5.6, 5.7]Cochran-Mantel-Haenszel
Comparison: At Week 4p-value: 0.089195% CI: [-2.3, 12.7]Cochran-Mantel-Haenszel
Comparison: At Week 6p-value: 0.844795% CI: [-12.1, 3.7]Cochran-Mantel-Haenszel
Comparison: At Week 8p-value: 0.417495% CI: [-7.5, 9.4]Cochran-Mantel-Haenszel
Comparison: At Week 10p-value: 0.275695% CI: [-5.8, 11.2]Cochran-Mantel-Haenszel
Primary
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).
Time frame: At Weeks 2, 4, 6, and 8
Population: Full Analysis Population: subset of subjects in the randomized population who were dispensed study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | WI-NRS 4-point Responder Rate at Weeks 2 4, 6, and 8 | Responders at Week 8 | 40 Participants |
| Placebo | WI-NRS 4-point Responder Rate at Weeks 2 4, 6, and 8 | Responders at Week 2 | 19 Participants |
| Placebo | WI-NRS 4-point Responder Rate at Weeks 2 4, 6, and 8 | Responders at Week 4 | 29 Participants |
| Placebo | WI-NRS 4-point Responder Rate at Weeks 2 4, 6, and 8 | Responders at Week 6 | 35 Participants |
| Serlopitant 5 mg | WI-NRS 4-point Responder Rate at Weeks 2 4, 6, and 8 | Responders at Week 6 | 38 Participants |
| Serlopitant 5 mg | WI-NRS 4-point Responder Rate at Weeks 2 4, 6, and 8 | Responders at Week 8 | 37 Participants |
| Serlopitant 5 mg | WI-NRS 4-point Responder Rate at Weeks 2 4, 6, and 8 | Responders at Week 4 | 24 Participants |
| Serlopitant 5 mg | WI-NRS 4-point Responder Rate at Weeks 2 4, 6, and 8 | Responders at Week 2 | 18 Participants |
Comparison: At Week 2p-value: 0.565195% CI: [-10.1, 8.7]Cochran-Mantel-Haenszel
Comparison: At Week 4p-value: 0.776995% CI: [-14.8, 6.7]Cochran-Mantel-Haenszel
Comparison: At Week 6p-value: 0.328595% CI: [-9.1, 14.8]Cochran-Mantel-Haenszel
Comparison: At Week 8p-value: 0.652595% CI: [-14.4, 9.8]Cochran-Mantel-Haenszel
Primary
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).
Time frame: At Week 10
Population: Full Analysis Population: subset of subjects in the randomized population who were dispensed study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Worst Itch Numeric Rating Scale 4-point Responder Rate at Week 10 | 46 Participants |
| Serlopitant 5 mg | Worst Itch Numeric Rating Scale 4-point Responder Rate at Week 10 | 44 Participants |
Comparison: At Week 10p-value: 0.586195% CI: [-13.9, 11.1]Cochran-Mantel-Haenszel
Secondary
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.
Time frame: 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.
Population: Safety Population - Subset of subjects who received at least one dose of study medication
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 38 Participants |
| Placebo | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs Leading to Treatment Discontinuation | 2 Participants |
| Placebo | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs Likely Related to Study Drug | 3 Participants |
| Placebo | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Serious TEAEs | 0 Participants |
| Serlopitant 5 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Serious TEAEs | 2 Participants |
| Serlopitant 5 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 49 Participants |
| Serlopitant 5 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs Likely Related to Study Drug | 12 Participants |
| Serlopitant 5 mg | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs Leading to Treatment Discontinuation | 2 Participants |
Secondary
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.
Time frame: At Week 10
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Concentrations of Serlopitant and Metabolites | Met-Serl-M1/M1a | 0.2 nmol/L | Standard Deviation 2.02 |
| Placebo | Plasma Concentrations of Serlopitant and Metabolites | Met-Serl-M2/M2a | 0.1 nmol/L | Standard Deviation 0.81 |
| Placebo | Plasma Concentrations of Serlopitant and Metabolites | Met-Serl-M3 | 0.0 nmol/L | Standard Deviation 0.46 |
| Placebo | Plasma Concentrations of Serlopitant and Metabolites | Serlopitant | 0.3 nmol/L | Standard Deviation 3.09 |
| Serlopitant 5 mg | Plasma Concentrations of Serlopitant and Metabolites | Serlopitant | 634.6 nmol/L | Standard Deviation 441.07 |
| Serlopitant 5 mg | Plasma Concentrations of Serlopitant and Metabolites | Met-Serl-M1/M1a | 150.8 nmol/L | Standard Deviation 120.33 |
| Serlopitant 5 mg | Plasma Concentrations of Serlopitant and Metabolites | Met-Serl-M3 | 60.9 nmol/L | Standard Deviation 39.43 |
| Serlopitant 5 mg | Plasma Concentrations of Serlopitant and Metabolites | Met-Serl-M2/M2a | 41.6 nmol/L | Standard Deviation 26.69 |