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

• Sponsor: Vyne Therapeutics Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03841331
• Collaborator: (none)
• Enrollment: 233
• Locations: 41
• Arms: 2
• Actual Duration (Months): 12
• Patients Per Site: 5.7
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Pruritus	Drug: 5 mg Serlopitant Tablets; Drug: Matching Placebo Tablets	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 233 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy, Safety, and Tolerability of Serlopitant for the Treatment of Chronic Pruritus of Unknown Origin
• Actual Study Start Date: Jan 22, 2019
• Actual Primary Completion Date: Dec 10, 2019
• Actual Study Completion Date: Jan 21, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 5 mg Serlopitant Tablets Serlopitant Tablets	Drug: 5 mg Serlopitant Tablets; Serlopitant Tablets; Other Names: VPD-737
Placebo Comparator: 5 mg Placebo Tablets Placebo Tablets	Drug: Matching Placebo Tablets; Placebo Tablets

Outcome Measures

Primary Outcome Measures

1. 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).

2. 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).

3. 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.

4. 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.

5. 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.

6. 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.

Secondary Outcome Measures

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Study Site 221	Hot Springs	Arkansas	United States	72022
2	Study Site 823	Bakersfield	California	United States	93301
3	Study Site 204	Fremont	California	United States	94538
4	Study Site 803	Los Angeles	California	United States	90045
5	Study Site 820	Centennial	Colorado	United States	80112
6	Study Site 804	Denver	Colorado	United States	80210
7	Study Site 811	Aventura	Florida	United States	33180
8	Study Site 801	Jacksonville	Florida	United States	32256
9	Study Site 807	Miami	Florida	United States	33137
10	Study Site 331	Miami	Florida	United States	33144
11	Study Site 824	Sarasota	Florida	United States	34239
12	Study Site 818	West Palm Beach	Florida	United States	33406
13	Study Site 349	Savannah	Georgia	United States	31406
14	Study Site 814	Indianapolis	Indiana	United States	46250
15	Study Site 808	Brighton	Massachusetts	United States	02135
16	Study Site 822	Rolla	Missouri	United States	65401
17	Study Site 371	Saint Joseph	Missouri	United States	64506
18	Study Site 817	Saint Louis	Missouri	United States	63110
19	Study Site 821	Bellevue	Nebraska	United States	68123
20	Study Site 813	Las Vegas	Nevada	United States	89128
21	Study Site 387	Las Vegas	Nevada	United States	89148
22	Study Site 816	Morristown	New Jersey	United States	07960
23	Study Site 121	Ocean Township	New Jersey	United States	07712
24	Study Site 802	Bronx	New York	United States	10458
25	Study Site 507	Brooklyn	New York	United States	11203
26	Study Site 341	High Point	North Carolina	United States	27262
27	Study Site 810	Raleigh	North Carolina	United States	27612
28	Study Site 524	Dublin	Ohio	United States	43016
29	Study Site 116	Portland	Oregon	United States	97202
30	Study Site 522	Pittsburgh	Pennsylvania	United States	15213
31	Study Site 345	Johnston	Rhode Island	United States	02919
32	Study Site 815	Warwick	Rhode Island	United States	02886
33	Study Site 805	Nashville	Tennessee	United States	37215
34	Study Site 365	Austin	Texas	United States	78745
35	Study Site 120	Dallas	Texas	United States	75231
36	Study Site 819	Fort Worth	Texas	United States	76244
37	Study Site 359	Pflugerville	Texas	United States	78660
38	Study Site 809	San Antonio	Texas	United States	78229
39	Study Site 217	Norfolk	Virginia	United States	23502
40	Study Site 806	Spokane	Washington	United States	99202
41	Study Site 812	Walla Walla	Washington	United States	09362

Sponsors and Collaborators

• Vyne Therapeutics Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Feb 11, 2019
• Statistical Analysis Plan - Jan 30, 2020

More Information

Publications

None provided.

• Responsible Party: Vyne Therapeutics Inc.
• ClinicalTrials.gov Identifier: NCT03841331
• Other Study ID Numbers: MTI-117
• First Posted: Feb 15, 2019
• Last Update Posted: May 20, 2021
• Last Verified: May 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Vyne Therapeutics Inc.: Pruritus
• Additional relevant MeSH terms: Pruritus; Serlopitant

Study Results

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 Detail	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.

Arm/Group Title	Placebo	Serlopitant 5 mg
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	117	116
COMPLETED	108	106
NOT COMPLETED	9	10

Baseline Characteristics

Arm/Group Title	Placebo	Serlopitant 5 mg	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	117	116	233
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.1 (12.05)	60.7 (13.60)	59.4 (12.89)
Sex: Female, Male (Count of Participants)
Female	93 79.5%	83 71.6%	176 75.5%
Male	24 20.5%	33 28.4%	57 24.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.9%	1 0.9%	2 0.9%
Asian	4 3.4%	4 3.4%	8 3.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	15 12.8%	7 6%	22 9.4%
White	95 81.2%	102 87.9%	197 84.5%
More than one race	0 0%	2 1.7%	2 0.9%
Unknown or Not Reported	2 1.7%	0 0%	2 0.9%

Outcome Measures

1. Primary Outcome

Title	Worst Itch Numeric Rating Scale 4-point Responder Rate at Week 10
Description	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

Outcome Measure Data

Analysis Population Description

Full Analysis Population: subset of subjects in the randomized population who were dispensed study medication.

Arm/Group Title	Placebo	Serlopitant 5 mg
Arm/Group Description	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.	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.
Measure Participants	117	116
Count of Participants [Participants]	46 39.3%	44 37.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 10
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5861
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-1.4
	Confidence Interval	(2-Sided) 95%; -13.9 to 11.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% Wald confidence intervals for the treatment difference was used

2. Primary Outcome

Title	WI-NRS 4-point Responder Rate at Weeks 2 4, 6, and 8
Description	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

Outcome Measure Data

Analysis Population Description

Full Analysis Population: subset of subjects in the randomized population who were dispensed study medication.

Arm/Group Title	Placebo	Serlopitant 5 mg
Arm/Group Description	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.	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.
Measure Participants	117	116
Responders at Week 2	19 16.2%	18 15.5%
Responders at Week 4	29 24.8%	24 20.7%
Responders at Week 6	35 29.9%	38 32.8%
Responders at Week 8	40 34.2%	37 31.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5651
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -10.1 to 8.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% Wald confidence intervals for the treatment difference was used.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7769
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-4.1
	Confidence Interval	(2-Sided) 95%; -14.8 to 6.7
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		95% Wald confidence intervals for the treatment difference was used.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 6
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3285
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	2.8
	Confidence Interval	(2-Sided) 95%; -9.1 to 14.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% Wald confidence intervals for the treatment difference was used.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 8
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6525
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	-2.3
	Confidence Interval	(2-Sided) 95%; -14.4 to 9.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% Wald confidence intervals for the treatment difference was used.

3. Primary Outcome

Title	WI-NRS 3-point Responder Rate at Weeks 2, 4, 6, 8, and 10
Description	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

Outcome Measure Data

Analysis Population Description

Full Analysis Population: subset of subjects in the randomized population who were dispensed study medication.

Arm/Group Title	Placebo	Serlopitant 5 mg
Arm/Group Description	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.	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.
Measure Participants	117	116
Responders at Week 2	6 5.1%	6 5.2%
Responders at Week 4	8 6.8%	14 12.1%
Responders at Week 6	15 12.8%	10 8.6%
Responders at Week 8	14 12%	15 12.9%
Responders at Week 10	13 11.1%	16 13.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4952
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Treatment effect
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -5.6 to 5.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% Wald confidence intervals for the treatment difference was used.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0891
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Treatment effect
	Estimated Value	5.2
	Confidence Interval	(2-Sided) 95%; -2.3 to 12.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% Wald confidence intervals for the treatment difference was used.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 6
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8447
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Treatment effect
	Estimated Value	-4.2
	Confidence Interval	(2-Sided) 95%; -12.1 to 3.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% Wald confidence intervals for the treatment difference was used.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 8
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4174
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Treatment effect
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; -7.5 to 9.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% Wald confidence intervals for the treatment difference was used.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 10
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2756
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Treatment effect
	Estimated Value	2.7
	Confidence Interval	(2-Sided) 95%; -5.8 to 11.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% Wald confidence intervals for the treatment difference was used.

4. Primary Outcome

Title	Change From Baseline in WI-NRS at Weeks 2, 4, 6, 8, and 10
Description	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

Outcome Measure Data

Analysis Population Description

Full Analysis Population: subset of subjects in the randomized population who were dispensed study medication.

Arm/Group Title	Placebo	Serlopitant 5 mg
Arm/Group Description	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.	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.
Measure Participants	117	116
Baseline (Observed value)	8.37 (0.929)	8.44 (0.855)
Change from Baseline at Week 2	-1.65 (2.115)	-1.61 (1.961)
Change from Baseline at Week 4	-2.41 (2.382)	-2.46 (2.349)
Change from Baseline at Week 6	-2.83 (2.624)	-2.94 (2.495)
Change from Basline at Week 8	-2.99 (2.647)	-2.97 (2.562)
Change from Baseline at Week 10	-3.34 (2.787)	-3.25 (2.545)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4409
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 95%; -0.49 to 0.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5496
	Comments	At week 4
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.65 to 0.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 6
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6311
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.11
	Confidence Interval	(2-Sided) 95%; -0.78 to 0.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 8
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.4738
	Confidence Interval	(2-Sided) 95%; -0.65 to 0.69
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 10
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3948
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 95%; -0.60 to 0.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Primary Outcome

Title	Change From Baseline in Daily WI-NRS Scores Through Week 2
Description	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

Outcome Measure Data

Analysis Population Description

Full Analysis Population: subset of subjects in the randomized population who were dispensed study medication.

Arm/Group Title	Placebo	Serlopitant 5 mg
Arm/Group Description	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.	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.
Measure Participants	117	116
Baseline (observed value)	8.37 (0.929)	8.44 (0.855)
Change from Baseline at Day 1	-0.22 (0.879)	-0.09 (0.819)
Change from Baseline at Day 2	-0.85 (1.836)	-0.69 (1.264)
Change from Baseline at Day 3	-0.94 (1.788)	-0.77 (1.348)
Change from Baseline at Day 4	-1.16 (1.977)	-0.96 (1.459)
Change from Baseline at Day 5	-1.34 (2.103)	-0.99 (1.495)
Change from Baseline at Day 6	-1.33 (2.174)	-1.15 (1.892)
Change from Baseline at Day 7	-1.44 (2.331)	-1.35 (1.758)
Change from Baseline at Day 8	-1.35 (2.171)	-1.35 (1.746)
Change from Baseline at Day 9	-1.53 (2.210)	-1.35 (1.996)
Change from Baseline at Day 10	-1.63 (2.460)	-1.41 (2.023)
Change from Baseline at Day 11	-1.73 (2.333)	-1.69 (2.211)
Change from Baseline at Day 12	-1.67 (2.280)	-1.58 (2.247)
Change from Baseline at Day 13	-1.82 (2.335)	-1.75 (2.291)
Change from Baseline at Day 14	-1.92 (2.518)	-1.74 (2.266)

6. Primary Outcome

Title	Change From Baseline in Worst-Itch Visual Analog Scale at Weeks 2, 4, 6, and 10
Description	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

Outcome Measure Data

Analysis Population Description

Full Analysis Population: subset of subjects in the randomized population who were dispensed study medication.

Arm/Group Title	Placebo	Serlopitant 5 mg
Arm/Group Description	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.	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.
Measure Participants	117	116
Baseline (Observed Value)	82.09 (10.741)	83.53 (11.941)
Change from Baseline at Week 2	-22.96 (27.425)	-20.52 (28.825)
Change from Baseline at Week 4	-27.01 (28.906)	-28.28 (29.731)
Change from Baseline at Week 6	-32.83 (31.046)	-30.92 (31.487)
Change from Baseline at Week 10	-37.64 (31.613)	-37.42 (32.986)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2440
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.44
	Confidence Interval	(2-Sided) 95%; -4.98 to 9.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6349
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.27
	Confidence Interval	(2-Sided) 95%; -9.20 to 6.65
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 6
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.91
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.3407
	Confidence Interval	(2-Sided) 95%; -6.40 to 10.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 10
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4960
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.23
	Confidence Interval	(2-Sided) 95%; -8.52 to 8.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Description	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.

Outcome Measure Data

Analysis Population Description

Safety Population - Subset of subjects who received at least one dose of study medication

Arm/Group Title	Placebo	Serlopitant 5 mg
Arm/Group Description	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.	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.
Measure Participants	117	116
TEAEs	38 32.5%	49 42.2%
TEAEs Leading to Treatment Discontinuation	2 1.7%	2 1.7%
TEAEs Likely Related to Study Drug	3 2.6%	12 10.3%
Serious TEAEs	0 0%	2 1.7%

8. Secondary Outcome

Title	Plasma Concentrations of Serlopitant and Metabolites
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Serlopitant 5 mg
Arm/Group Description	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.	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.
Measure Participants	117	116
Met-Serl-M1/M1a	0.2 (2.02)	150.8 (120.33)
Met-Serl-M2/M2a	0.1 (0.81)	41.6 (26.69)
Met-Serl-M3	0.0 (0.46)	60.9 (39.43)
Serlopitant	0.3 (3.09)	634.6 (441.07)

Adverse Events

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.
Adverse Event Reporting Description	Adverse events (AEs) and serious adverse events (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.
Arm/Group Title	Placebo		Serlopitant 5 mg
Arm/Group Description	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.		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.
All Cause Mortality
	Placebo		Serlopitant 5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/117 (0%)		0/116 (0%)
Serious Adverse Events
	Placebo		Serlopitant 5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/117 (0%)		2/116 (1.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastasis	0/117 (0%)	0	1/116 (0.9%)	1
Nervous system disorders
Intracranial mass	0/117 (0%)	0	1/116 (0.9%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	0/117 (0%)	0	1/116 (0.9%)	1
Other (Not Including Serious) Adverse Events
	Placebo		Serlopitant 5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/117 (0.9%)		12/116 (10.3%)
Gastrointestinal disorders
Diarrhoea	0/117 (0%)		8/116 (6.9%)
Nervous system disorders
Somnolence	1/117 (0.9%)		6/116 (5.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.